Imaging follow-up strategy after endovascular treatment of Intracranial aneurysms: A literature review and guideline recommendations.

OBJECTIVE: Endovascular coil embolization is the primary treatment modality for intracranial aneurysms. However, its long-term durability remains of concern, with a considerable proportion of cases requiring aneurysm reopening and retreatment. Therefore, establishing optimal follow-up imaging protocols is necessary to ensure a durable occlusion. This study aimed to develop guidelines for follow-up imaging strategies after endovascular treatment of intracranial aneurysms. METHODS: A committee comprising members of the Korean Neuroendovascular Society and other relevant societies was formed. A literature review and analyses of the major published guidelines were conducted to gather evidence. A panel of 40 experts convened to achieve a consensus on the recommendations using the modified Delphi method. RESULTS: The panel members reached the following consensus: 1. Schedule the initial follow-up imaging within 3-6 months of treatment. 2. Noninvasive imaging modalities, such as three-dimensional time-of-flight magnetic resonance angiography (MRA) or contrast-enhanced MRA, are alternatives to digital subtraction angiography (DSA) during the first follow-up. 3. Schedule mid-term follow-up imaging at 1, 2, 4, and 6 years after the initial treatment. 4. If noninvasive imaging reveals unstable changes in the treated aneurysms, DSA should be considered. 5. Consider late-term follow-up imaging every 3-5 years for lifelong monitoring of patients with unstable changes or at high risk of recurrence. CONCLUSIONS: The guidelines aim to provide physicians with the information to make informed decisions and provide patients with high-quality care. However, owing to a lack of specific recommendations and scientific data, these guidelines are based on expert consensus and should be considered in conjunction with individual patient characteristics and circumstances.

Injection of a PMMA-doped MSC spheroid gel for the treatment of painful osteoporotic vertebral compression fractures.

We aimed to develop a biocompatible treatment to overcome the limitations of polymethyl methacrylate (PMMA) vertebroplasty for osteoporotic compression fracture patients. We synthesized an injectable hydrogel containing PMMA. Mesenchymal stem cell (MSC) spheroids were included in the injectable PMMA-doped gel (= PMMA-doped spheroid gel). In vitro, the osteogenic/anti-inflammatory effects of the embedded spheroids were investigated by the quantitative real-time polymerase chain reaction method. In vivo, we used ovariectomy (OVX)-induced osteoporotic rats with injured femurs to investigate the pain-relief effects. The OVX rats were divided into four groups according to the materials injected (non, PMMA, PMMA gel, and PMMA-spheroid gel) into the lesion. The immunofluorescence (IF) intensity levels of painful markers in dorsal root ganglia (DRG) were measured. In vitro, a volumetric ratio of the gel of 8 (gel):2 (PMMA) was non-cytotoxic for MSCs and promoted the expression of osteogenic/anti-inflammatory markers. In vivo, the values of several bone parameters in the PMMA-doped spheroid gel group showed remarkable increases compared to those in the PMMA group. In addition, the IF intensity levels of the painful markers were noticeably decreased in the PMMA-spheroid gel group. We, therefore, suggest that this treatment can be useful for osteoporotic vertebral compression fracture patients.

Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury.

BACKGROUND: Neural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation. METHODS: siRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats. RESULTS: The knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted. CONCLUSIONS: These findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.

Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages.

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.

Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State: Recommendations for Doctors with Less Expertise at Local Emergency Rooms.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

The Association between Parkinson's Disease and Congestive Heart Failure in Korea: A Nationwide Longitudinal Cohort Study.

The purpose of this nationwide longitudinal follow-up study is to investigate the relationship between Parkinson's disease (PD) and congestive heart failure (CHF) patients in Korea. Patient data were collected using the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. The International Classification of Diseases 10-CM code G-20 distinguished 6475 PD patients who were enrolled in the PD group. After removing 1039 patients who were not hospitalized or attended an outpatient clinic less than twice, the total number of participants was reduced to 5436 individuals. Then, 177 patients diagnosed before 1 January 2004 were removed for relevancy, leaving us with 5259 PD patients. After case-control matching was completed using 1:5 age- and gender-coordinated matching, 26,295 people were chosen as part of the control group. The Cox proportional hazards regression analysis and the Kaplan-Meier technique were used to assess the risk of CHF in patients with Parkinson's disease. After controlling for age and gender, the hazard ratio of CHF in the PD group was 5.607 (95% confidence interval (CI), 4.496-6.993). After that, the hazard ratio of CHF in the PD group was modified against for comorbid medical disorders, resulting in a value of 5.696 (95% CI, 4.566-7.107). In subgroup analysis, CHF incidence rates were significantly increased in the PD group compared to the control group (males and females; aged ≥ 65 and <65; the non-diabetes and diabetes, hypertension and non-hypertension, and dyslipidemia and non-dyslipidemia subgroups). This nationwide longitudinal study shows a higher incidence rate of CHF in PD patients.

Intrawound Vancomycin Powder Application for Preventing Surgical Site Infection Following Cranioplasty.

OBJECTIVE: Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics. METHODS: This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated. RESULTS: Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4-333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006-0.762; adjusted OR, 0.068; 95% CI, 0.006-0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up. CONCLUSION: Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.

Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study.

OBJECTIVE: The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. METHODS: From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. RESULTS: According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). CONCLUSIONS: The risk rate of IS increased in patient with pyogenic spondylitis.

Transplantation of neuron-inducing grafts embedding positively charged gold nanoparticles for the treatment of spinal cord injury.

In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague-Dawley rats (NSC-pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with ß-tubulin III [also called Tuj1]) was significantly increased in the NSC-pGNP gel group (***p < 0.001) compared to those of two control groups (NSC and NSC gel groups) in the SCI conditions. The NSC-pGNP gel group showed the lowest differentiation into astrocytes (stained with glial fibrillary acidic protein). Regeneration of damaged axons (stained with biotinylated dextran amines) within the lesion was two-fold higher in the NSC-pGNP gel group than that in the NSC gel group. The highest locomotor scores were also found in the NSC-pGNP gel group. These outcomes suggest that neuron-inducing pGNP gel graft embedding embryonic spinal cord-derived NSCs can be a useful type of stem cell therapy after SCI.

The Relationship between Parkinson's Disease and Acute Myocardial Infarction in Korea : A Nationwide Longitudinal Cohort Study.

OBJECTIVE: The goal of the following statewide age and gender-coordinated cohort study in Korea is to find out if there is a link between acute myocardial infarction (AMI) and Parkinson's disease (PD). METHODS: Utilizing the National Health Insurance Sharing Service cohort, patient data were collected. Six thousand four hundred seventy-five individuals with PD were distinguished by utilizing the International Classification of Diseases 10 code G20 and have enrolled in the PD group. The number of participants decreased to 5259 after excluding 1039 patients who were hospitalized less than one time or who visited an outpatient clinic less than twice. Then, 26295 individuals were selected as part of the control group after case control matching was conducted through 1 : 5 age- and gender-coordinated matching. The Cox proportional hazard regression analysis and Kaplan-Meier method were utilized to analyze the likelihood of AMI in PD. RESULTS: After controlling for age and gender, the hazard ratio of AMI in the PD group was 3.603 (95% confidence interval [CI], 2.837-4.577). After that, the following hazard ratio of AMI in the PD group was modified against for co-morbid medical disorders, resulting in 3.551 (95% CI, 2.795-4.511). According to a subgroup analysis, in males and females aged <65 and aged ≥65 and in the non-diabetes and diabetes, hypertension and non-hypertension, dyslipidemia and non-dyslipidemia subgroups, the AMI incidence rates were dramatically higher in the PD group compared to that of the control. CONCLUSION: Individuals with PD have a greater chance of AMI, according to this cross-national study.

Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages.

The purpose of this study is to elucidate the anti-inflammatory effect of lobeglitazone (LOBE) in lipopolysaccharide (LPS)-induced bone-marrow derived macrophages (BMDMs). We induced nitric oxide (NO) production and pro-inflammatory gene expression through LPS treatment in BMDMs. The changes of NO release and expression of pro-inflammatory mediators by LOBE were assessed via NO quantification assay and a real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the regulatory effect of LOBE on activation of mitogen-activated protein kinase (MAPK) signaling pathway was investigated by measuring the phosphorylation state of extracellular regulatory protein (ERK) and c-Jun N-terminal kinase (JNK) proteins by Western blot. Our results show that LOBE significantly reduced LPS-induced NO production and pro-inflammatory gene expression of interleukin-1ß (IL-1ß), IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1). Moreover, LOBE reduced phosphorylation levels of ERK and JNK of MAPK signaling pathway. In conclusion, LOBE exerts an anti-inflammatory effect in LPS-induced BMDMs by suppression of NO production and pro-inflammatory gene expression, and this effect is potentially through inhibition of the MARK signaling pathway.

Association of Parkinson's disease with ischemic stroke in Korea: A nationwide longitudinal cohort study in Korea.

OBJECTIVE: The aim of this nationwide age- and sex- matched longitudinal follow up study is to determine the risk of Parkinson's disease (PD) associated with ischemic stroke in Korea. METHODS: Patient data were collected from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). PD was identified using the International Classification of Diseases (ICD) 10-CM code G 20. In total, 6,475 patients were enrolled in the PD group from the NHISS. After subtracting 1,039 patients who underwent hospitalization less than once or those who visited an outpatient clinic less than two times, 5,259 patients who were diagnosed after January 1, 2004 ultimately participated in this study. After case-control match was done through 1:5 age- and sex- stratified matching, 26,295 individuals were chosen as control. Kaplan-Meier method and Cox proportional hazard regression analysis were performed to evaluate the risk of ischemic stroke in PD. RESULTS: The hazard ratio of ischemic stroke in the PD group was 3.848 (95% confidence interval (confidence interval [CI]): 3.14-4.70) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in PD group was 3.885 (95% CI: 3.17-4.75) after adjusting for comorbidities. According to subgroup analysis, in male and female and non-diabetes and diabetes and non-hypertension and hypertension and dyslipidemia and non-dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in the PD group than those in the control group. CONCLUSIONS: This nationwide longitudinal study suggests an increased risk of ischemic stroke in PD patients.

Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model.

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.

Direct Injection of Hydrogels Embedding Gold Nanoparticles for Local Therapy after Spinal Cord Injury.

In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.

Transplantation of tauroursodeoxycholic acid-inducing M2-phenotype macrophages promotes an anti-neuroinflammatory effect and functional recovery after spinal cord injury in rats.

OBJECTIVES: In this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)-induced M2-phenotype (M2) macrophages and their ability to promote anti-neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model. METHODS: To this end, compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF), we evaluated whether TUDCA effectively differentiates bone marrow-derived macrophages (BMDMs) into M2 macrophages. RESULTS: The M2 expression markers in the TUDCA-treated BMDM group were increased more than those in the GM-CSF-treated BMDM group. After the SCI and transplantation steps, pro-inflammatory cytokine levels and the mitogen-activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA-induced M2 group more than they were in the GM-CSF-induced M1 group and in the TUDCA group. Moreover, the TUDCA-induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM-CSF-induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)-labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA-induced M2 group more than those in the GM-CSF-induced M1 group and the TUDCA group. CONCLUSIONS: This study demonstrates that the transplantation of TUDCA-induced M2 macrophages promotes an anti-neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA-induced M2 macrophages represents a possible alternative cell therapy for SCI.

Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.

Inhibitory Effects of Gold and Silver Nanoparticles on the Differentiation into Osteoclasts In Vitro.

Gold nanoparticles (GNPs) have been widely studied to inhibit differentiation into osteoclasts. However, reports of the inhibitory effects of silver nanoparticles (SNPs) during the process of differentiation into osteoclasts are rare. We compared the inhibitory effect of GNPs and SNPs during the process of differentiation into osteoclasts. Bone marrow-derived cells were differentiated into osteoclasts by the receptor activator of the nuclear factor-kappa-Β ligand (RANKL). The inhibitory effect of GNPs or SNPs during the process of differentiation into osteoclasts was investigated using tartrate-resistant acid phosphatase (TRAP) and actin ring staining. The formation of TRAP positive (+) multinuclear cells (MNCs) with the actin ring structure was most inhibited in the SNP group. In addition, the expression of specific genes related to the differentiation into osteoclasts, such as c-Fos, the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP, and Cathepsin K (CTSK) were also inhibited in the SNP groups. As a result, the levels related to differentiation into osteoclasts were consistently lower in the SNP groups than in the GNP groups. Our study suggests that SNPs can be a useful material for inhibiting differentiation into osteoclasts and they can be applied to treatments for osteoporosis patients.

Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury.

Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 µg/20 µL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1ß) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-ß) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.

Safety and Tolerability of Stromal Vascular Fraction Combined with ß-Tricalcium Phosphate in Posterior Lumbar Interbody Fusion: Phase I Clinical Trial.

The rates of pseudarthrosis remain high despite recent advances in bone graft substitutes for spinal fusion surgery. The aim of this single center, non-randomized, open-label clinical trial was to determine the feasibility of combined use of stromal vascular fraction (SVF) and ß-tricalcium phosphate (ß-TCP) for patients who require posterior lumbar interbody fusion (PLIF) and pedicle screw fixation. Two polyetheretherketone (PEEK) cages were inserted into the intervertebral space following complete removal of the intervertebral disc. The PEEK cage (SVF group) on the right side of the patient was filled with ß-TCP in combination with SVF, and the cage on the left side (control group) was filled with ß-TCP alone. Fusion rate and cage subsidence were assessed by lumbar spine X-ray and CT at 6 and 12 months postoperatively. At the 6-month follow-up, 54.5% of the SVF group (right-sided cages) and 18.2% of the control group (left-sided cages) had radiologic evidence of bone fusion (p = 0.151). The 12-month fusion rate of the right-sided cages was 100%, while that of the left-sided cages was 91.6% (p = 0.755). Cage subsidence was not observed. Perioperative combined use of SVF with ß-TCP is feasible and safe in patients who require spinal fusion surgery, and it has the potential to increase the early bone fusion rate following spinal fusion surgery.

Impact of Time Interval between Index Event and Stenting on Periprocedural Risk in Patients with Symptomatic Carotid Stenosis.

OBJECTIVE: The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting. METHODS: This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0-3, 4-7, 8-10, 11-14, 15-21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093-14.489]; p=0.036). Stenting in Day 0-3 (13.2%; OR, 10.997 [95% CI, 2.333-51.826]; p=0.002) and Day 4-7 (8.3%; OR, 6.775 [95% CI, 1.382-33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8-10, 1.8%; Day 11-14, 2.5%; Day 15-21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553-3.352]; p<0.001). The high risk for radiological events was maintained in all time intervals (Day 0-3 : 55.3%; OR, 2.224 [95% CI, 1.103-4.627]; p=0.026; Day 4-7 : 58.3%; OR, 2.543 [95% CI, 1.329-4.949]; p=0.005; Day 8-10 : 53.6%; OR, 2.096 [95% CI, 1.138-3.889]; p=0.018; Day 11-14 : 57.5%; OR, 2.458 [95% CI, 1.225-5.021]; p=0.012; Day 15-21 : 55.6%; OR, 2.271 [95% CI, 1.099-4.764]; p=0.028; Day >21 : 54.8%; OR, 2.203 [95% CI, 1.342-3.641]; p=0.002). CONCLUSION: This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.