Efficacy, safety, and cost-effectiveness analysis of Cerebrolysin in acute ischemic stroke: A rapid health technology assessment.

This study conducts a rapid health technology assessment to systematically evaluate the effectiveness, safety, and cost-effectiveness of Cerebrolysin as an adjunctive therapy for acute ischemic stroke to provide evidence-based medicine for clinical decisions of Cerebrolysin. All systematic reviews/meta-analyses, pharmacoeconomic studies, and health technology assessment reports of Cerebrolysin for the treatment of acute ischemic stroke before August 17, 2023, were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Weipu, Sinomed database and the official website of health technology assessment. According to the inclusion and exclusion criteria, 2 researchers independently carried out screening, data extraction, and quality evaluation and descriptively analyzed the results of the included studies. A total of 14 pieces of literature were incorporated, comprising 8 systematic reviews/meta-analyses and 6 pharmacoeconomic studies. In terms of effectiveness, compared to control groups, the use of Cerebrolysin as a treatment for acute ischemic stroke demonstrates certain advantages, including enhancement in total efficacy rate, neurological function, upper limb motor dysfunction, and facilitation of the recovery of activities of daily living. Especially in patients with moderate to severe acute ischemic stroke, Cerebrolysin has demonstrated the ability to enhance neurological function recovery and ameliorate disabilities. Regarding safety, adverse reactions were mild or comparable to those in the control group. The primary findings of economic studies reveal that advocating for the use of Cerebrolysin offers certain cost-effectiveness advantages. Cerebrolysin contributes to improved clinical efficacy and evaluation indexes while demonstrating favorable safety and economic benefits.

Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling.

OBJECTIVE: To investigate the role of exosomal miRNAs from synovial fluid (SF) in osteoarthritis (OA) patients and investigate the underlying molecular mechanism. METHODS: Degenerated knee tissues were collected from male and female OA patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the differences in the expression of inflammatory indicators, including TNF-α, IL-6, and IL-10, between the degenerative and injury groups. Exosomes were isolated from SF using the Exoquick kit, and a microarray was used to identify differentially expressed miRNAs (DEmiRNAs), which were analyzed using bioinformatics. The predicted relationship between DEmiRNAs and target genes was verified using a luciferase reporter gene assay. CCK-8 and transwell assays were used to assess cell viability and migration. Immunofluorescence and TUNEL assay were used to detect cell autophagy and apoptosis. The interaction between proteins was detected by immunoprecipitation and verified by Mab rescue assay. RESULTS: The relative expression of TNF-α/IL6 was significantly higher in the degeneration group than in the injury group. The OA degeneration group released significantly more and smaller exosomes than the injury group. The expression of miR-182-5p was markedly reduced in OA patients and had a higher correlation with inflammatory indicators. Tumor necrosis factor α-induced protein 8 (TNFAIP8) was a target of miR-182-5p, and its overexpression promoted chondrocyte proliferation, migration, and invasion and enhanced the wound healing efficiency. We also found a direct interaction of TNFAIP8 with autophagy-related gene 3 (ATG3). TNFAIP8 triggered ATG3 LC3-mediated autophagy. CONCLUSION: The downregulation of exosomal miR-182-5p inhibits OA degeneration by targeting TNFAIP8 via the ATG/LC3 pathway.

Postoperative Upper-limb Palsy After Posterior Percutaneous Endoscopic Cervical Foraminotomy and Discectomy.

BACKGROUND: Postoperative upper-limb palsy (ULP) is a serious complication after cervical spine surgery. ULP after posterior percutaneous endoscopic cervical foraminotomy and discectomy (PPCED) has not yet been reported. OBJECTIVE: To introduce cases of postoperative ULP after PPCED and associated risk factors. STUDY DESIGN: A single-center, retrospective, observational study. SETTING: Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China. METHODS: From January 2016 through January 2022, PPCED involving a total of 663 segments was performed in 610 patients with radiculopathy who were diagnosed with cervical radiculopathy or mixed cervical spondylosis caused by foraminal stenosis or posterolateral disc herniation. RESULTS: PPCED was successfully completed in 610 patients, 6 of whom (0.98%) developed ULP. Two patients were diagnosed with double-segment cervical nerve root canal stenosis (C4/5/6, C5/6/7) and 2 with migrated cervical disc soft herniation (a magnetic resonance image of one showed a migrated disc herniation downward from C4/5 in the sagittal plane; another showed this upward from C5/6); one patient was diagnosed with C5/6 intervertebral foraminal stenosis, and one had simple C4/5 lateral disc herniation. Postoperative ULP rates for C4/5 (2/30, 6.67%) and C5/6 (2/177, 1.13%) were much higher than those for the other levels. Anatomically, the width of the intervertebral foramen on computed tomography was 2.3 ± 1.12 mm in ULP cases, which was significantly lower than that in non-ULP cases (3.4 ± 1.83, P < 0.05). This suggests that preoperative foramen width correlates highly negatively with postoperative ULP incidence. LIMITATIONS: This was a single-center, retrospective, nonrandomized study with a low level of evidence. CONCLUSIONS: PPCED is a good treatment for cervical radiculopathy. The rate of postoperative ULP after PPCED is much lower than that after posterior cervical foraminotomy. Perturbation to the C5 (or C6) nerve root, thermal injury due to burr use or the radiofrequency applied, and marked foraminal stenosis are possible relevant factors associated with postoperative ULP.

Surgical management of concurrent lateral ankle instability and osteochondral lesions of the talus increases dynamic sagittal ankle range of motion.

PURPOSE: A biomechanical study, in which imaging modalities are used to strictly include patients with concurrent lateral ankle instability (LAI) and osteochondral lesions of the talus (OLT), is needed to demonstrate the static and dynamic ankle range of motion (ROM) restriction in these patients, and determine whether ankle ROM restriction can be corrected postoperatively. METHODS: Eight patients with concurrent LAI and OLT treated with the arthroscopic modified Broström procedure and microfracture were recruited from June 2019 to January 2020. Patients were assessed using outcome scales, static ankle ROM, and a stair descent gait analysis for dynamic ankle ROM, a day prior to surgery and one year postoperatively. Eight healthy subjects were assessed using the same modalities upon recruitment. Operative outcomes and variables during stair descent were documented and compared among the preoperative, postoperative, and healthy groups. A curve analysis, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalised time series. RESULTS: The functional outcomes of patients with concurrent LAI and OLT were significantly worse than those of healthy subjects preoperatively, but were partially improved postoperatively. Patients had decreased static and dynamic ROM preoperatively, and static ROM did not significantly increase postoperatively (preoperative, 39.6 ± 11.3; postoperative, 44.9 ± 7.1; healthy, 52.0 ± 4.6; p = 0.021). Patients showed increased dynamic ankle flexion ROM (preoperative, 41.2 ± 11.6; postoperative, 53.6 ± 9.0; healthy, 53.9 ± 3.4; p = 0.012) postoperatively, as well as increased peroneus longus activation (preoperative, 35.8 ± 12.0; postoperative, 55.4 ± 25.1; healthy, 71.9 ± 13.4; p = 0.002) and muscle co-contraction of the tibialis anterior and peroneus longus (preoperative, 69.4 ± 23.4; postoperative, 88.4 ± 9.3; healthy, 66.2 ± 18.1; p = 0.045). CONCLUSIONS: Patients with concurrent LAI and OLT had decreased static and dynamic sagittal ankle ROM and altered neuromuscular activation patterns. The arthroscopic modified Broström procedure and microfracture did not significantly increase the static sagittal ankle ROM. However, the dynamic sagittal ankle ROM, peroneus longus activation and muscle co-contraction of the tibialis anterior and peroneus longus increased postoperatively. LEVEL OF EVIDENCE: IV.

Investigation on the contour and bone mineral density of the distal tibial cutting surface used for total ankle arthroplasty.

PURPOSE: This study was designed to investigate (1) the contour of the distal tibial cutting surface, and (2) the bone mineral density (BMD) of the distal tibial cutting surface used during total ankle arthroplasty (TAA). METHODS: Eight-four distal tibial models were created using foot and ankle computerized tomographic (CT) images taken from normal people. The distal tibial cutting surface for TAA was determined to be 10 mm proximal to the tibial plafond. The bony contour and BMD values were determined from the CT image at that level. A bounding box was made on the contour and the width and length of the contour was measured. Regional BMD was evaluated by Hounsfield units (HU) value measurement, with 7 regions of interest (ROI) on 8 different directions for all the 84 CT images. Two different observers made independent measurements and mean HU values for all the 56 ROIs were calculated. RESULTS: Great variations were found among the contours of the cutting surface especially in term of the shape of the anterior and posterior tibial tubercle, and the fibular notch. These variations could be grouped into six categories. For the BMD of the cutting surface, the medial border of the cutting surface did not included cortical bone. The HU value of seven ROIs, which included cortical bone, were significantly greater than all the other ROIs. Few statistical differences were found by multiple comparisons among HU value of all the 49 ROIs without cortex. CONCLUSIONS: Great variability existed in the shape and the BMD of the distal tibial cutting surface.

Positive and negative factors for the treatment outcomes following total ankle arthroplasty? A systematic review.

BACKGROUND: Patient selection, surgeon's experience and implant design play an integral role and affect the treatment outcomes of total ankle arthroplasty (TAA). The aims of this study were to investigate the positive and negative attributes that correlate with different clinical and radiographic outcomes. METHODS: Eight-nine studies matched the inclusion criteria: (1) studies of primary TAA with uncemented prosthesis; (2) mean follow-up of no less than 2-year; (3) reports of clinical and radiographic outcomes, and exclusion criteria: (1) non-English study; (2) more than one type of prosthesis without separated data; (3) kin studies with shorter follow-up or smaller cohort. Age, etiology, preoperative deformity, surgeon's experience, follow-up duration and prosthetic type were studied with respect to different outcomes by mixed-effects logistic regression analysis. RESULTS: Patients factor: older patients reported less pain or stiffness and demonstrated less radiographic loosening which did not require additional surgical intervention. More traumatic arthritis experienced adjacent joints degeneration after TAA. Surgeon factor: less experienced surgeons had more intraoperative complications. Lack of experience for complications management without implant retrieval during early period might result in more revisions or fusion was done. Prosthetic factor: updated instrumentation decreased malalignment. If the polyethylene (PE) insert was significantly narrower than the metal components more implant instability and subsequent severe particulate wear was seen. Designs with flat-on-flat articulation and ridge at the center of the talar component associated with more PE fracture. Minimal bone resection reduced postoperative fractures. A flat cut of the tibial component and a flat undersurface with press-fit by two screws or pegs of the talar component demonstrated less postoperative fractures, whereas a syndesmosis fusion and a small triangular shape with one central fin of the talar component experienced more loosening which did not require additional surgery. Anatomic conical shape of the talar component seemed to reduce adjacent joint degeneration. Finally, fewer failures were found in patients who received HINTEGRA and Salto Talaris. CONCLUSIONS: Based on our investigation, some positive and negative factors for different clinical and radiographic outcomes were found, which should be taken into consideration in clinical practice and ankle implant design.

Talar Dome Investigation and Talocrural Joint Axis Analysis Based on Three-Dimensional (3D) Models: Implications for Prosthetic Design.

Ankle joint kinematics is mainly stabilized by the morphology of the talar dome and the articular surface of tibiofibular mortise as well as the medial and lateral ligament complexes. Because of this the bicondylar geometry of talus dome is believed to be crucial for ankle implant design. However, little data exist describing the precise anatomy of the talar dome and the talocrural joint axis. The aim of this study is to document the anatomy of the talar dome and the axis of the talocrural joint using three-dimensional (3D) computed tomographic (CT) modeling. Seventy-one participants enrolled for CT scanning and 3D talar model reconstruction. All the ankles were held in a neutral position during the CT scanning. Six points on the lateral and medial crest of the talar dome were defined. The coordinate of the six points; radii of lateral-anterior (R-LA), lateral-posterior (R-LP), medial-anterior (R-MA), and medial-posterior (R-MP) sections; and inclination angle of the talar dome were measured, and the inclination and deviation angles of the talocrural joint axis were determined. The mean values of R-LA, R-LP, R-MA, and R-MP were 19.23 ± 2.47 mm, 18.76 ± 2.90 mm, 17.02 ± 3.49 mm, and 22.75 ± 3.04 mm. The mean inclination angle of the talar dome was 9.86 ± 3.30 degrees. Gender variation was found in this parameter. The mean inclination and deviation angles were 8.60 ± 0.07 and 0.76 ± 0.69 degrees for the dorsiflexion axis and -7.34 ± 0.07 and 0.09 ± 0.18 degrees for the plantarflexion axis. Bilateral asymmetries between the medial and lateral crest of the talar dome were found, which resulted in different dorsiflexion and plantarflexion axes of the talocrural joint. Currently, no ankle implants replicate this talar anatomy, and these findings should be considered in future implant designs.

In vivo kinematics of functional ankle instability patients during the stance phase of walking.

BACKGROUND: Previous studies showed functional ankle instability (FAI) patients have morphological ligamentous abnormality, despite having no apparent joint laxity. RESEARCH QUESTION: Whether tibiotalar and subtalar joints hypermobility exists in FAI patients during stance phase of walking, remains controversial. METHODS: Ten unilateral FAI patients, ten unilateral lateral ankle sprain (LAS) copers and ten healthy controls were included. A dual fluoroscopy imaging system was utilized to capture the fluoroscopic images of tibiotalar and subtalar joint during the stance phase of walking. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint excursions about six degrees of freedom were compared among the three groups. The correlations between range of motion and Cumberland Ankle Instability Tool (CAIT) scores were assessed utilizing the Spearman's correlation coefficient (r). RESULTS: During the stance phase, the FAI patients and LAS copers showed larger tibiotalar anterior/posterior translation than the healthy controls (FAI patients, p = .013; LAS copers, p = .002). The FAI patients also showed significantly larger lateral/medial translation (p = .035) and inversion/eversion rotation (p = .003) of subtalar joints than healthy controls. By contrast, the subtalar joints of the LAS copers were not different from those of the healthy controls in the lateral/medial translation (p = .459) and inversion/eversion rotation (p = .091). CAIT scores were negatively correlated with range of motion. SIGNIFICANCE: During the stance phase of walking, FAI patients showed significantly larger hypermobility of subtalar joints than healthy controls, contrary to the LAS copers. These findings justify the utilization of dual fluoroscopy imaging system to detect joint hypermobility in FAI patients. Treatment for FAI patients may require stabilization of the subtalar joint.

Effects of an ankle brace on the in vivo kinematics of patients with chronic ankle instability during walking on an inversion platform.

BACKGROUND: As in vivo tibiotalar and subtalar joint kinematics are not currently known following the application of an ankle brace, an investigation of these kinematics may provide insight into the mechanisms of ankle braces. RESEARCH QUESTION: This study aimed to determine the effect of an ankle brace on in vivo kinematics of patients with chronic ankle instability. METHODS: Eleven patients with chronic ankle instability were recruited in this study. A dual fluoroscopic imaging system and a solid modeling software were utilized to calculate the joint positions of the participants as they walked barefooted on a level platform, walked barefooted on a 15° inversion platform, and walked with an ankle brace on a 15° inversion platform. The joint positions during the three walking conditions were compared. RESULTS: Tibiotalar joints were more inverted (pose 2, p = .004), and subtalar joints were more anteriorly translated (pose 2-6, p = .003), more plantarflexed (pose 2, p = .008; pose 3, p = .013; pose 5, p = .008; pose 6, p = .016) and more inverted (pose 1-5, p = .003; pose 6, p = .013) during barefooted walking on the inversion platform than during walking on the level platform. The inversion of subtalar joints was decreased after the brace application (pose 2-4, p = .003; pose 5, p = .004; pose 7, p = .016). SIGNIFICANCE: Brace application reduced the increased subtalar inversion induced by the inversion platform. Nevertheless, increased subtalar anterior translation and plantarflexion persisted after brace application. The ankle brace might be beneficial for clinical populations with increased subtalar inversion.

Effect of a Semirigid Ankle Brace on the In Vivo Kinematics of Patients with Functional Ankle Instability during the Stance Phase of Walking.

An ankle brace is commonly used by patients after they suffer from initial ankle sprains, reducing the incidents of recurrent sprain or limiting laxity in joints with functional ankle instability (FAI). However, whether the application of a semirigid ankle brace can improve the abnormal ankle gait kinematics of patients with FAI remains unknown. This study aimed to determine the effect of a semirigid ankle brace on the gait kinematics of ankle joints through 3D-2D fluoroscopy image registration. A total of 8 subjects with FAI (3 males and 5 females, 10 feet) as FAI group and 10 subjects without FAI (6 males and 4 females, 10 feet) as control group were enrolled in this study. Three-dimensional bone models created from computed tomography images were matched to fluoroscopic images to compute the 6 degrees of freedom (DOF) talocrural, subtalar, and ankle joints complex kinematics for control and FAI group with or without brace during the stance phase of walking. FAI patients had significantly less ROMs in inversion/eversion rotation of the talocrural and subtalar joint after wearing semirigid ankle brace. Laxity was observed in most of the displacements of the talocrural and subtalar joints in FAI group. The brace partly altered the ankle joints movement in opposite directions, especially joint rotation, and restricted the talocrural and subtalar joints in the dorsiflexion position during the touch down phase of walking.

Gender Variation in the Shape of Superior Talar Dome: A Cadaver Measurement Based on Chinese Population.

Understanding the shape of superior talar dome is essential for a better size compatibility between talar component of ankle implant and bone. The purpose of this study was to determine whether there were gender variations in (1) width (TW) and length (TL) of talus, as well as anterior width (DAW), middle width (DMW), posterior width (DPW), and length (DL) of superior talar dome; (2) differences between the DAW, DMW, and DPW; (3) the ratios between these parameters. Fifty-one cadaveric ankle specimens were included. Two observers measured all the specimens using vernier caliper. Intraclass correlation coefficients (ICCs) were used for intraobserver and interobserver reliability analysis and the reliability was thought to be good if the ICC>0.75. A two-tailed unpaired t-test or the rank-sum test was used to investigate gender variations. A single-factor ANOVA was utilized to identify the differences between the width of the superior talar dome surface and p value of <0.05 was considered significant. Intraobserver and interobserver reliability were good. Significant gender variations were found, in which TW, TL, DAW, DMW, DPW, and DL of female specimens were much smaller than those of male. The width of talar dome linearly decreased from DAW to DPW; however, the linearly decreased rate from anterior to posterior width was bigger in female. Moreover, significant differences were found in DAW/DPW, DMW/DPW, DL/DAW, DL/DMW, and DL/DPW between male and female. Based on our result, there was no difference in the 2D shape of the whole talus instead gender variation existed in the 2D shape of superior talar dome between male and female. The current 2D data could contribute to figure out more suitable size of talar component for Chinese population and might indicate a gender-specific shape of bone-implant interface, which could reduce the potential bone-component incompatibility when performing ankle replacement using standard component.

TRIM44, a crucial target of miR-410, functions as a potential oncogene in osteosarcoma.

PURPOSE: Mounting evidence highlights the essential role of TRIM44 in tumor initiation and malignant progression in several cancers; however, the function of TRIM44 in osteosarcoma (OS) remains unknown. In this study, we aim to investigate the role of TRIM44 and reveal its regulation by deregulated miRNAs in OS. MATERIALS AND METHODS: The expression profiles of TRIM44 were examined by immunohistochemistry, Western blotting, and qRT-PCR. The biological functions of TRIM44 were investigated through siRNA-mediated knockdown experiments. The regulation of TRIM44 by miR-410 was confirmed by Western blotting, dual luciferase reporter assays, and rescue experiments. RESULTS: TRIM44 was upregulated in OS tissues and cell lines, and its overexpression was positively correlated with TNM stage, metastasis, and recurrence. Knockdown of TRIM44 in OS cells suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In addition, we identified TRIM44 as a novel target gene of miR-410 and miR-410 was remarkably downregulated in OS. Moreover, overexpression of miR-410 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition of OS cells by directly targeting TRIM44 expression. Furthermore, reintroduction of TRIM44 partially reversed miR-410-induced inhibitory effects on OS cells. CONCLUSION: Collectively, our findings indicate that the miR-410/TRIM44 link is critical in the control of OS progression.