Deep brain stimulation of the subthalamic nucleus increases the risk of sialorrhea in patients with advanced Parkinson's disease.

INTRODUCTION: Sialorrhea is a common neurological manifestation of Parkinson's disease (PD). No specifically designed prospective study has tested the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on sialorrhea in patients with advanced PD. We focused on the effect of STN-DBS on the incidence of sialorrhea in patients with PD. METHODS: This multicenter, prospective, non-randomized concurrent clinical trial analyzed the incidence of sialorrhea during long-term follow-up in 170 patients with advanced PD (84 patients with STN-DBS and 86 patients with medication therapy). RESULTS: After STN-DBS, 58.1% of patients presented with sialorrhea (Drooling Rating Scale (DRS) > 5) compared with 39.3% of patients with medication therapy (P < 0.001). STN-DBS stimulation demonstrated a significant increase in DRS and Drooling Severity and Frequency Scale (DSFS) compared with the patients with medication therapy (P < 0.001). At follow-up, the onabotulinumtoxin-A (BTX-A) injection ratio was significantly higher in the STN-DBS group (29.8% vs. 11.9%, P = 0.0057) compared with the patients with medication therapy. CONCLUSIONS: STN-DBS increased the risk of sialorrhea in patients with advanced PD. TRIAL REGISTRATION: clinicaltrials. gov (NCT06090929).

Fully Endoscopic Microvascular Decompression for Trigeminal Neuralgia Caused by Vertebrobasilar Artery: A Case Series Review: 2-Dimensional Operative Video.

BACKGROUND AND OBJECTIVE: Microvascular decompression (MVD) is the most definitive and preferred surgical treatment for trigeminal neuralgia (TN). Treatment of TN caused by the vertebrobasilar artery (VBA) has been reported to be challenging and less satisfactory in complications and recurrence. Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize brain tissue stretch injury while exploring the trigeminal nerve. However, there are few retrospective studies on the treatment of TN caused by VBA by fully endoscopic microvascular decompression (E-MVD). This article aimed to illustrate the safety and efficacy of E-MVD for TN caused by the VBA. METHODS: Clinical data for 26 patients with TN caused by the VBA who underwent E-MVD from 2019 to 2022 were retrospectively analyzed. The characteristics of vertebrobasilar-associated TN were summarized. The safety and efficacy of E-MVD for vertebrobasilar-associated TN were estimated based on the analysis of intraoperative manipulation, postoperative symptom relief, and complications. RESULTS: Intraoperatively, the vertebrobasilar artery was regarded as a direct offending vessel in all 26 patients with TN, the vertebral artery in 18 (69.23%) and the basilar artery in 10 (38.46%). In addition to the vertebrobasilar artery, other vessels involved included the superior cerebellar artery in 12 patients, anterior inferior cerebellar artery in 9, posterior inferior cerebellar artery in 1, and veins in 4. All patients underwent E-MVD, and TN was entirely resolved in 26 (100%) patients immediately postoperatively. During the follow-up period of 12-45 months, no recurrence or serious complications were found. There were no serious postoperative complications, such as cerebellar swelling, intracranial hemorrhage, or death. CONCLUSION: E-MVD for vertebrobasilar-associated TN is effective and safe.

Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages.

PURPOSE: The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. METHOD: GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. RESULT: The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. CONCLUSION: These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.

Acute Visual Impairment in a Patient with Parkinson's Disease after Successful Bilateral Subthalamic Nucleus Deep Brain Stimulation with Low-Dose Levodopa: A Case Report.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is widely used for the treatment of primary motor symptoms in patients with Parkinson's disease (PD). Further, recent evidence suggests that STN-DBS may relieve a few ophthalmic symptoms in PD, such as eye-blink rate and the flexibility of eye saccades. However, its exact effect on visual function remains unknown. Herein, we report the case of a patient with PD who underwent STN-DBS and experienced visual symptoms following levodopa reduction. CASE PRESENTATION: A 63-year-old male patient with PD developed severe visual impairment after six months of high-frequency STN-DBS. His symptoms resolved after adjusting the levodopa dose prescribed to the patient. CONCLUSIONS: This case report suggests that DBS is beneficial in patients with PD in terms of eye-blink rate. However, the rapid reduction of medication after STN-DBS may lead to retinal atrophy and the shrinkage of vessel density in the ocular fundus. Thus, neurosurgeons should pay close attention to patients with visual symptoms when adjusting levodopa dosages.

Accuracy of additively manufactured zirconia four-unit fixed dental prostheses fabricated by stereolithography, digital light processing and material jetting compared with subtractive manufacturing.

OBJECTIVE: To evaluate the manufacturing accuracy of zirconia four-unit fixed dental prostheses (FDPs) fabricated by three different additive manufacturing technologies compared with subtractive manufacturing. METHODS: A total of 79 zirconia FDPs were produced by three different manufacturing technologies, representing additive (one stereolithography [aSLA] and one material jetting [aMJ] device, two digital light processing [aDLP1/aDLP2] devices) and subtractive manufacturing (two devices [s1/s2]), the latter serving as references. After printing, additively manufactured FDPs were debound and finally sintered. Subsequently, samples were circumferentially digitized and acquired surface areas were split in three Regions Of Interest (ROIs: inner/outer shell, margin). Design and acquired data were compared for accuracy using an inspection software. Statistical evaluation was performed using the root mean square error (RMSE) and nonparametric Kruskal-Wallis method with post hoc Wilcoxon-Mann-Whitney U tests. Bonferroni correction was applied in case of multiple testing. RESULTS: Regardless the ROI, significant differences were observed between manufacturing technologies (P < 0.001). Subtractive manufacturing was the most accurate with no significant difference regarding the material/device (s1/s2, P > 0.054). Likewise, no statistical difference regarding accurary was found when comparing s2 with aMJ and aSLA in most ROIs (P > 0.085). In general, mean surface deviation was< 50 µm for s1/s2 and aMJ and< 100 µm for aSLA and aDLP2. aDLP1 showed surface deviations> 100 µm and was the least accurate compared to the other additive/subtractive technologies. SIGNIFICANCE: Additive manufacturing represents a promising set of technologies for the manufacturing of zirconia FDPs, but not yet as accurate as subtractive manufacturing. Methodological impact on accuracy within and in between different additive technologies needs to be further investigated.

Myricetin Loaded Nano-micelles Delivery System Reduces Bone Loss Induced by Ovariectomy in Rats Through Inhibition of Osteoclast Formation.

In recent years, much attention has been paid to the therapeutic effects of phytochemicals on osteoporosis. Other studies have shown that myricetin (MY) could promote osteogenic activity and inhibit osteoclastic effect, albeit little is known about effect of MY micellar system on osteoporosis. Therefore, we sought to discuss the therapeutic effect and mechanism of MY-loaded bone-targeting micelles on osteoporosis induced by ovariectomy (OVA) in rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles were prepared via ethanol injection method, while in vitro release study, bone targeting, pharmacokinetic studies, and the effect on proliferation of osteoblasts were investigated. Further, the therapeutic effect on osteoporosis was studied through ovariectomized rats. Compared with free MY, oral bioavailability of AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles in rats was increased by 3.54 times. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles exhibited bone targeting potential, and could significantly increase the activity of alkaline phosphatase and promote the proliferation of osteoblasts. Importantly, AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles mainly regulated bone metabolism by inhibiting bone resorption, thereby improving the symptoms of osteoporosis in OVA rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles substantially enhanced the oral bioavailability of MY and demonstrated good bone targeting capability, thereby suggesting its prospect as carrier for osteoporotic improvement in OVA rats.

An Innovative Approach to Manganese-Substituted Hydroxyapatite Coating on Zinc Oxide⁻Coated 316L SS for Implant Application.

In this paper, the synthesis of porous manganese substituted hydroxyapatite (Mn-HAp) coating on zinc oxide (ZnO) coated stainless steel (316L SS) using the electrodeposition technique is reported. The structural, functional, morphological, and elemental analyses are characterized by various analytical techniques including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Results of electrochemical techniques such as cyclic polarization and impedance show that the Mn-HAp coating on ZnO coated 316L SS has the highest corrosion resistance in simulated body fluid (SBF) solution. Moreover, dissolution of metal ions was extremely reduced, as evaluated by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The adhesion and hardness of Mn-HAp/ZnO bilayer coatings have superior mechanical properties over individual coatings. Further, the biocompatibility of in vitro osteoblast attachment, cell viability, and live/dead assessment also confirmed the suitability of Mn-HAp/ZnO bilayer coating on 316L SS for orthopedic applications.

[Clinical study on Thread-tooth Arc-track Screw Plate System through expandable channels in the treatment of lumbar instability diseases].

OBJECTIVE: To evaluate the validity and reliability of Thread-tooth Arc-track Screw Plate System (TASPS) in the fixation fusion through expandable channels. METHODS: From August 2007 to August 2010, 108 patients with lumbar instability were treated with surgery, including 61 males and 47 females, ranging in age from 26 to 57 years, with an average of 41 years. All the patients were divided into two groups : minimally invasive fusion group and traditional operation group (54 patients in each group). The patients in the minimally invasive fusion group were treated with self-designed TASPS to conduct the fixation fusion through expandable channels by minimally invasive pedicle screw; and the patients in traditional operation group were treated with traditional interbody fixation fusion by pedicle screw. The data were collected and investigated at the 1st week, 3rd month and 1st year postoperatively. The comparative parameters of two groups contained the total operation time, the implanted time, the total amount of bleeding; the VAS score, ODI score and improvement rate at each investigated period; the intervertebral space height of preoperative and postoperative periods; the inefficiency rate of implantation and the fusion rate of postoperative period. RESULTS: All incisions were healed by first stage without any complications such as dural tear, injury of nerve root or cauda equine, intervertebral space infection. The patients in the minimally invasive fusion group needed longer operative time than that of the traditional operation group, but had less total amount of intraoperative and postoperative bleeding and shorter implanted time of pedicle screw than those of the traditional operation group. The VAS scores of two groups at the 1st week after operation significantly decreased compared with that of the 1st day before the operation, and the difference was of high statistical significance. And the VAS scores of two groups at the 3rd month and 1st year after operation also significantly decreased compared with that of the 1st day before the operation, and the difference was highly statistically significant. By comparing the VAS score and ODI score at the 1st week, 3rd month and 1st year postoperatively, the results showed that the VAS score and ODI score of the minimally invasive fusion group were all lower than those of the traditional operation group, and the differences were of high statistical meaningfulness. After 1 year, the improvement rate of the minimally invasive fusion group was (77.46 +/- 6.34)%, while that of the traditional operation group was (72.73 +/- 4.49)%, and the difference was highly statistically significant (P < 0.01). The intervertebral space heights of two groups remarkably increased. At the 3rd month after operation, the difference of intervertebral space heights of the two groups was of no statistical significance. At the 1st year after operation, intervertebral space heights of the two groups were lost to some extent, but the height of the minimally invasive fusion group was higher than that of the traditional operation group, and the difference was statistically significant. The fusion rates of the two groups after 1 year were 100%. CONCLUSION: The fixation fusion through expandable channels by minimally invasive pedicle screw possesses the characteristics of fewer traumas, less intraoperative blood loss, less postoperative pain and rapid recovery. Since its intervertebral fusion rate is similar to the open surgery, it can be viewed as one effective approach for the treatment of lumbar instability diseases. And TASPS is reasonably designed, easy to install and reliably fixed with good reduction effect, which can be applied through expandable channels.