To corset or not to corset after lumbar spine fixation surgery?: A prospective randomized clinical trial and literature review.

PURPOSE: Orthosis after lumbar fusion surgery is common. However, the evidence for benefit remains to be determined, especially in tropical areas with heavy workers. To investigate postoperative orthosis and whether it affects pain improvement, quality of life, and fusion rate. METHOD: From May 2021 to May 2022, this single-center prospective randomized clinical trial enrolled 110 patients. We excluded 9 patients, and 101 people were analyzed finally. Corset group, in which participants used a corset for 3 months postoperatively; Non-corset group, in which participants didn't wear any orthosis. ODI and VAS scale were recorded before the surgery: 2 weeks, 1 month, 3 months, half a year, and 1 year postoperatively. The lumbar X-ray was done before the surgery, 6 months postoperatively. All complications in 1 year were recorded. RESULTS: Significant decrease in VAS score in the non-corset group since post-operation day 5 (corset group 3.44 ±â€…1.77, non-corset group 3.36 ±â€…1.75, P = .0093) during admission, and also a decrease in admission duration (corset group 11.08 ±â€…2.39, non-corset group 9.55 ±â€…1.75, P = .0004) were found. There was a significantly better ODI score in the non-corset group since post-operation 1 month, while in the corset group until post-operation 3 months. Both groups had no significant difference in satisfaction, complication rates, and X-ray results, such as fusion, angular rotation, sagittal transition, and slip in the neutral position. CONCLUSION: After the transpedicular screw fixation with posterolateral fusion surgery for degenerative spondylolisthesis, non-orthosis is a safe strategy. It can reduce the admission duration and has the trend for better functional outcomes.

Analysis of effectiveness and outcome of traumatic brain injury treatment in ED during COVID-19 pandemic: A multicenter in Taiwan.

The coronavirus disease 2019 has become a threat to global healthcare because of its rapid spread and evolution. In severe cases, the initial management of the disease is mainly supportive therapy and mechanical ventilation. Therefore, we investigated whether a modified emergency department workflow affects the efficacy will influence the efficacy and patient outcomes of traumatic brain injury (TBI) in Taiwan. This retrospective observational study used the Chang Gung Research Database in Taiwan from 7 hospitals in the Chang Gung Memorial Hospital System. Clinical index parameters and treatment efficiencies were analyzed between the locally transmitted period (January 20, 2020-June 7, 2020, period 2) and the community spread period (May 19, 2021-July 27, 2021, period 4) with the same interval of the pre-pandemic in 2019 as a reference period. During the locally transmitted period, only the time interval for patients who had to wait for a brain CT examination was, on average, 7.7 minutes shorter, which reached statistical significance. In addition, the number of TBI patients under 18 years of age decreased significantly during the community spread period. The "Door to the operating room (OR)," with polymerase chain reaction (PCR) testing, was on average 109.7 minutes slower than without the PCR testing in the reference period 2019. TBI treatment efficiency was delayed because of the PCR test. However, the surgical volume and functional outcome during these 2 periods were statistically insignificant compared to the pre-pandemic period because the spread of the virus was well controlled and hospital capacity was increased.

Current Indications for Spinal Endoscopic Surgery and Potential for Future Expansion.

Endoscopic spine surgery (ESS) has evolved as a safe, effective, and efficient alternative for minimally invasive spine surgery (MISS). The innovation of full-endoscopic systems makes definitive decompression surgery through different approaches feasible. The approach can be determined according to the location of the target lesion or the surgeon's preference. During the past 2 decades, ESS has expanded its indications from lumbar to cervical spines. Except for decompression, endoscopy-assisted fusion surgery is also developing. However, ESS is still evolving and has a steep learning curve. The revolution of technologies and ESS techniques will enable surgeons to treat various spinal diseases more practically. In recent years, the application of the computer-assisted navigation system and augmented reality have reformed imaging quality and interpretation. The endoscopic rhizotomy techniques have opened a new way for MISS of chronic low back pain. This review introduces the current indications of ESS and its potential future expansion.

Complications of Full-Endoscopic Lumbar Discectomy versus Open Lumbar Microdiscectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Endoscopic lumbar discectomy has been an alternative for treating lumbar disc herniation. Evidence-based study for the benefit zone of full-endoscopic lumbar discectomy (FELD) is necessary. The study compared the complication risks between the FELD and open discectomy or microdiscectomy. METHODS: The literature search was from 4 online databases for randomized controlled trials (RCTs) and cohort studies. The meta-analysis of different study designs was conducted separately. Complication rates were considered primary outcomes, and the recurrence and revision rates were considered secondary outcomes. RESULTS: Six RCTs and thirteen cohort studies met the eligibility criteria. The meta-analysis was conducted separately. From the pooled RCT meta-analysis, the overall complication rates of FELD and open discectomy/microdiscectomy were 5.5% and 10.4%, respectively. The moderate-quality evidence suggested that FELD had a lower risk of overall complications (risk ratio [RR] = 0.55, 95% confidence interval [CI] = 0.31-0.98). There was no significant difference in specific complications and recurrence. The analysis of cohort studies revealed no significant difference in overall complications, but there was significant heterogeneity in the results. The risk of dural injury was significantly lower for FELD (RR = 0.46, 95% CI = 0.22-0.96). The pooled meta-analysis from cohort studies suggested a higher risk of transient dysesthesia (RR = 3.70, 95% CI = 1.54-8.89), residual fragment (RR = 5.29, 95% CI = 2.67-10.45), and revision surgeries (RR = 1.53, 95% CI = 1.12-2.08) for FELD. CONCLUSIONS: The current evidence showed a lower risk of overall complications for FELD. The quality of evidence was moderate to low, and the risk of bias from the primary literature should be concerned.

Curcumin-Loaded Oil-Free Self-Assembled Micelles Inhibit the Influenza A Virus Activity and the Solidification of Curcumin-Loaded Micelles for Pharmaceutical Applications.

Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much less investigated. In this study, the optimized self-assembled micelles of RH 40/Tween 80 loaded with curcumin (Cur-M) in an oil-free-based system were spherical with a hydrodynamic size at 13.55 nm ± 0.208 and polydispersity at 0.144 characterized by atomic force microscopy and dynamic light scattering, respectively. Additionally, Cur-M significantly increased the bioactivity/stability of curcumin and effectively inhibited the influenza A virus infection and its replication after viral entry, indicating the alteration of the inhibition mechanisms of curcumin against virus infection via RH 40/Tween 80 micelle formulation. Furthermore, a solid formulation (Cur-SM) of Cur-M was successfully developed by a one-pot physical adsorption method using a small amount of adsorbent and ~50% of curcumin/Cur-M that could be burst released from Cur-SM in 1 h, facilitating the fast-releasing applications. Ultimately, all of the results show that Cur-SM acts as a good nano-formulation of curcumin with improved solubility/dispersity in aqueous solutions and demonstrate new anti-influenza mechanisms of curcumin for pharmaceutical development.

In-hospital outcomes of patients with spontaneous supratentorial intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) in the brain parenchyma accounts for 16.1% of all stroke types in Taiwan. It is responsible for high morbidity and mortality in some underlying causes. The objective of this study is to discover the predicting factors focusing on in-hospital outcomes of patients with spontaneous supratentorial ICH. Between June 2014 and October 2018, there were a total of 159 patients with spontaneous supratentorial ICH ranging from 27 to 91 years old in our institution. Twenty-three patients died during hospitalization, whereas 59 patients had an extended length of stay of >30 days. The outcomes were measured by inpatient death, length of stay, and activity of daily living (ADL). Both univariate and multivariate binary logistic regression, as well as multivariate linear regression, were used for statistical analysis. Multivariate binary linear regression analysis showed the larger hematoma in initial computed tomography scan of >30 cm3 (odds ratio [OR] = 2.505, P = .013) and concurrent in-hospital infection (OR = 4.173, P = .037) were both statistically related to higher mortality. On the other hand, in-hospital infection (≥17.41 days, P = .000) and surgery (≥11.23 days, P = .001) were correlated with a longer length of stay. Lastly, drastically poor change of ADL (ΔADL <-30) was associated with larger initial ICH (>30 cc, OR = 2.915, P = .049), in-hospital concurrent infection (OR = 4.695, P = .01), and not receiving a rehabilitation training program (OR = 3.473, P = .04). The results of this study suggest that age, prothrombin, initial Glasgow Coma Scale, computed tomography image, location of the lesion, and surgery could predict the mortality and morbidity of the spontaneous ICH, which cannot be reversed at the time of occurrence. However, effective control of international normalized ratio level, careful prevention against infection, and the aid of rehabilitation programs might be important factors toward a decrease of inpatient mortality rate, the length of stay, and ADL recovery.

Percutaneous radiofrequency trigeminal rhizotomy benefits in patients with refractory trigeminal neuralgia.

ABSTRACT: A significant number of patients suffers from refractory trigeminal neuralgia (TN) after receiving microvascular decompression (MVD) or other neuro-destructive procedure such as gamma knife radiosurgery (GKRS). This study aims to demonstrate a remediable, reproducible approach to treating refractory pain effectively by percutaneous radiofrequency trigeminal rhizotomy (RF-TR).A total of 392 patients with TN were treated by RF-TR during the past 10 years. Among these patients, 48 cases who had received either MVD, GKRS alone, or a combination of both were assigned to group A. Those who had not received any form of treatment (125 patients) or failed to respond medically (130 patients) were assigned as the control group (group B). All the RF-TR were performed by a single surgeon with the aid of intraoperative computed tomography (iCT)-based neuronavigation with magnetic resonance (MR) image fusion. The outcome measure was the numerical rating scale (NRS) expressed subjectively by patients. The paired Student t test and the analysis of covariance (ANCOVA) were used for statistical analysis.In group A, 21 of 24 patients (88%) had significant improvement (NRS change ≥5) in facial pain after RF-TR. The average NRS score was 9.75 ±â€Š0.53 before the procedure and 1.92 ±â€Š3.35 post-treatment (significant NRS decrease [P = .000]). On the other hand, in group B, 226 of 255 patients (89%) also had dramatic amelioration of facial pain after RF-TR. The average NRS score was 9.46 ±â€Š0.69 before the procedure and 1.62 ±â€Š2.85 post-treatment (7.84 ±â€Š2.82 in NRS decrease [P = .008]). By using a univariate ANCOVA, no statistical significance was found in NRS score improvement between the two groups.Repeated MVD and GKRS for refractory TN may be less desirable due to a greater risk of mortality (up to 0.8%) and morbidity (4% of serious complications). Conversely, RF-TR administration with the novel navigation technique by using iCT and MR image fusion is free from any remarkable and irreversible morbidities. In this study, RF-TR not only provided an alternative and effective strategy if TN recurred but also resulted in the same NRS score improvement regardless of the status of prior treatment.

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.

Percutaneous Radiofrequency Rhizotomy Is Equally Effective for Trigeminal Neuralgia Patients with or Without Neurovascular Compression.

BACKGROUND: Neurovascular compression (NVC) in patients with trigeminal neuralgia (TN) can be a factor of treatment outcome, especially in microvascular decompression and stereotactic radiosurgery. No such effect has been reported in percutaneous radiofrequency rhizotomy (RF). This study aims to investigate whether NVC affects the efficacy of RF in patients with TN. METHODS: We retrospectively reviewed patients with TN who received RF in our institution. Pretreatment magnetic resonance imaging was performed in every patient, and the presence of NVC was reviewed independently by two physicians. The patients were followed up at least for a year after the treatment. Pain severity was assessed with a numeric rating scale (NRS). RESULTS: Sixty-two patients were included in the study. All of the patients had single-sided lesions, and 35 patients had NVC. There were no significant differences between these two groups of patients in terms of gender distribution, age, and pretreatment pain severity. Comparable pain severity improvement was found at 1-year follow-up between these two groups (NRS 7.93 ± 0.492 without compression vs 7.57 ± 0.451 with compression, P = 0.600). No significant difference in posttreatment pain severity at 1 year was found between these two patient groups (NRS 1.37 ± 0.466 without compression vs 1.66 ± 0.458 with compression, P = 0.667). CONCLUSIONS: For patients with TN treated by RF, the presence or absence of NVC is not likely to affect the 1-year pain control rate.

Analysis of neurosurgical procedures with unplanned reoperation for quality improvement: A 5-year single hospital study.

ABSTRACT: The unplanned return to the operating room rate is a quality metric for assessing hospital performance. This study aimed to evaluate the cause, incidence, and time interval of unplanned returns in index neurosurgical procedures within 30 days of the initial surgery as an internal audit. We retrospectively analyzed neurosurgical procedures between January 2015, and December 2019, in a single regional hospital. The definition of an unplanned return to the operating room was a patient who underwent two operations within 30 days when the second procedure was not planned, staged, or related to the natural course of the disease.A total of 4365 patients were identified in our analysis, of which 93 (2%) had an unplanned return to the operating room within 30 days of their initial surgery during admission. The most common reason for an unplanned return to the operating room for a cranial procedure was hemorrhage, followed by hydrocephalus and subdural effusion, which accounted for 49.5%(46/93), 12%(11/93), and 5.4%(5/93) of cases, respectively. In spinal procedures, the most common cause of return was a residual disc, followed by surgical site infection, which accounted for 5.4%(5/93) and 4.3%(4/93) of cases, respectively. The overall median time interval for unplanned returns to the operating room was 3 days (interquartile range, 1-9).Lowering the rate of postoperative hemorrhage in cranial surgery and postoperative residual disc in spine surgery was crucial as an internal audit in a 5-year single institute follow-up. However, the unplanned reoperation rate is less helpful in benchmarking because of the heterogeneity of patients between hospitals.

Photochemical Internalization of Etoposide Using Dendrimer Nanospheres Loaded with Etoposide and Protoporphyrin IX on a Glioblastoma Cell Line.

Glioblastoma multiforme (GBM) is the most common malignant primary neoplasm of the adult central nervous system originating from glial cells. The prognosis of those affected by GBM has remained poor despite advances in surgery, chemotherapy, and radiotherapy. Photochemical internalization (PCI) is a release mechanism of endocytosed therapeutics into the cytoplasm, which relies on the membrane disruptive effect of light-activated photosensitizers. In this study, phototherapy by PCI was performed on a human GBM cell-line using the topoisomerase II inhibitor etoposide (Etop) and the photosensitizer protoporphyrin IX (PpIX) loaded in nanospheres (Ns) made from generation-5 polyamidoamine dendrimers (PAMAM(G5)). The resultant formulation, Etop/PpIX-PAMAM(G5) Ns, measured 217.4 ± 2.9 nm in diameter and 40.5 ± 1.3 mV in charge. Confocal microscopy demonstrated PpIX fluorescence within the endo-lysosomal compartment, and an almost twofold increase in cellular uptake compared to free PpIX by flow cytometry. Phototherapy with 3 min and 5 min light illumination resulted in a greater extent of synergism than with co-administered Etop and PpIX; notably, antagonism was observed without light illumination. Mechanistically, significant increases in oxidative stress and apoptosis were observed with Etop/PpIX-PAMAM(G5) Ns upon 5 min of light illumination in comparison to treatment with either of the agents alone. In conclusion, simultaneous delivery and endo-lysosomal co-localization of Etop and PpIX by PAMAM(G5) Ns leads to a synergistic effect by phototherapy; in addition, the finding of antagonism without light illumination can be advantageous in lowering the dark toxicity and improving photo-selectivity.

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.

The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation.

BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.

Effect of valproic acid on overall survival in patients with high-grade gliomas undergoing temozolomide: A nationwide population-based cohort study in Taiwan.

High-grade gliomas (HGGs) are a rapidly progressive and highly recurrent group of primary brain tumors. Despite aggressive surgical resection with chemoradiotherapy, prognoses remained poor. Valproic acid (VPA), a histone deacetylase inhibitor has shown the potential to inhibit glioma cell growth in vitro through several diverse mechanisms. However clinical studies regarding the effect of VPA on HGGs are limited. This study aimed to investigate whether using VPA in patients with HGGs under temozolomide (TMZ) would lead to a better overall survival (OS).We used the Taiwan National Health Insurance Research database to conduct this population-based cohort study. A total of 2379 patients with HGGs under TMZ treatment were included and were further classified into VPA (n = 1212, VPA ≥ 84 defined daily dose [DDD]) and non-VPA (n = 1167, VPA < 84 DDD) groups. Each patient was followed from 1998 to 2013 or until death. A Cox proportional hazard regression was performed to evaluate the effect of VPA and OS.The VPA group had a longer mean OS time compared with the non-VPA group (OS: 50.3 ±â€Š41.0 vs 42.0 ±â€Š37.2 months, P < .001). In patients between 18 and 40 years old, the difference is most significant (OS: 70.5 ±â€Š48.7 vs 55.1 ±â€Š46.0, P = .001). The adjusted hazard ratio is 0.81 (95% confidence interval, 0.72-0.91) for the VPA group relative to the non-VPA group.VPA at over 84 DDD improved OS in HGGs TMZ treatment.

Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells.

BACKGROUND: Glioblastoma multiforme (GBM) is the most severe type of primary brain tumor with a high mortality rate. Although extensive treatments for GBM, including resection, irradiation, chemotherapy and immunotherapy, have been tried, the prognosis is still poor. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug for the clinical treatment of GBM; however, its effects are very limited because of the chemoresistance. Valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitor activity, has been shown to have synergistic effects with TMZ against GBM. The mechanism of action of VPA on TMZ combination therapy is still unclear. Accumulating evidence has shown that secreted proteins are responsible for the cross talking among cells in the tumor microenvironment, which may play a critical role in the regulation of drug responses. METHODS: To understand the effect of VPA on secreted proteins in GBM cells, we first used the antibody array to analyze the cell culture supernatant from VPA-treated and untreated GBM cells. The results were further confirmed by lentivirus-mediated knockdown and exogenous recombinant administration. RESULTS: Our results showed that amphiregulin (AR) was highly secreted in VPA-treated cells. Knockdown of AR can sensitize GBM cells to TMZ. Furthermore, pretreatment of exogenous recombinant AR significantly increased EGFR activation and conferred resistance to TMZ. To further verify the effect of AR on TMZ resistance, cells pre-treated with AR neutralizing antibody markedly increased sensitivity to TMZ. In addition, we also observed that the expression of AR was positively correlated with the resistance of TMZ in different GBM cell lines. CONCLUSIONS: The present study aimed to identify the secreted proteins that contribute to the modulation of drug response. Understanding the full set of secreted proteins present in glial cells might help reveal potential therapeutic opportunities. The results indicated that AR may potentially serve as biomarker and therapeutic approach for chemotherapy regimens in GBM.

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.

Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of -14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.

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.