Background Current clinical decision tools for assessing the risk of symptomatic intracranial hemorrhage (sICH) in patients with vertebrobasilar artery occlusion (VBAO) who received endovascular treatment (EVT) have limited performance. This study develops and validates a clinical risk score to precisely estimate the risk of sICH in VBAO patients. Methods The derivation cohort recruited patients with VBAO who received EVT from the Posterior Circulation IschemIc Stroke Registry in China. Based on the posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS) evaluation method, the cohort was further divided into non-contrast CT (NCCT) and diffusion weighted imaging (DWI) cohorts to construct predictive models. sICH was diagnosed according to the Heidelberg Bleeding Classification within 48 hours of EVT. Clinical signature was constructed in the derivation cohort using machine learning and was validated in two additional cohorts from Asia and Europe. Results We enrolled 1843 patients who underwent EVT and had complete data. pc-ASPECTS of 1710 patients was evaluated on NCCT and 699 patients on DWI. In the NCCT cohort, 1364 individuals made up the training set, of whom 101 (7.4%) developed sICH. In the DWI cohort, the training set consisted of 560 individuals, with 44 (7.9%) experiencing sICH. Predictors of sICH were: glucose, pc-ASPECTS, time from estimated occlusion to groin puncture (EOT), poor collateral circulation, and modified Thrombolysis in Cerebral Infarction (mTICI) score. From these predictors, we derived the weighted poor collateral circulation-EOT-pc-ASPECTS-mTICI-glucose (PEACE) score. The PEACE score showed good discrimination in the training set (area under the curve (AUC) NCCT =0.85; AUC DWI =0.86), internal validation set (AUC NCCT =0.81; AUC DWI =0.82), and two additional external validation set (Asia: AUC NCCT =0.78, AUC DWI =0.80; Europe: AUC NCCT =0.74, AUC DWI =0.78). Conclusion The PEACE score reliably predicted the risk of sICH in VBAO patients who underwent EVT.
Objective
To introduce a novel lantern-shaped screw loaded with autologous bone and to assess the efficacy for the treatment of early osteonecrosis of the femoral head (ONFH) in a goat model.
Methods
Twenty-four goats with unilateral ONFH were induced. After core decompression, the goats were randomly divided into three groups. Group A, the goats were not given any treatment after model was established. Group B, the goats were treated by traditional core decompression combined with autograft. Group C, the goats were treated by core decompression utilizing lantern-shaped screw loaded with autologous bone. All the goats were given radiographic (X ray, CT scans) assessment at the time points of 4, 8, 12, 16 weeks postoperatively. Goats were sacrificed at the 16th week to evaluate the histological observation and biomechanical properties.
Results
Signs of typical osteonecrosis were found in group A, and collapse of the femoral head appeared at 16th week. After sixteen weeks, we found that the surface of femoral head was normal in group C; while an irregular surface or part of collapse was seen in group B. Histological and radiographic results both suggested that a continuous trabecular bone structure and thriving bone in-growth was abundant in the region of lantern-shaped support in group C. Fibrous tissue was obvious in group B with little bone in-growth. The strength of the femoral head was (42.15±0.65) mPa in group C, superior to group A and B significantly (P=0.000).
Conclusion
The progression of the collapse of the cartilage may be postponed by lantern-shaped screw loaded with autologous bone in the treatment of ONFH. It can not only provide appropriate circumstance to facilitate new bone remodeling but also strengthen biomechanical structure for the load-bearing region.
Key words:
Early osteonecrosis of the femoral head; Lantern-shaped screw; Autograft; Core decompression; Goat
Abstract The osteonecrotic area of steroid-induced avascular necrosis of the femoral head (SANFH) is a hypoxic microenvironment that leads to apoptosis of transplanted bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism remains unclear. Here, we explore the mechanism of hypoxic-induced apoptosis of BMSCs, and use the mechanism to improve the transplantation efficacy of BMSCs. Our results show that the long non-coding RNA AABR07053481 (LncAABR07053481) is downregulated in BMSCs and closely related to the degree of hypoxia. Overexpression of LncAABR07053481 could increase the survival rate of BMSCs. Further exploration of the downstream target gene indicates that LncAABR07053481 acts as a molecular “sponge” of miR-664-2-5p to relieve the silencing effect of miR-664-2-5p on the target gene Notch1 . Importantly, the survival rate of BMSCs overexpressing LncAABR07053481 is significantly improved after transplantation, and the repair effect of BMSCs in the osteonecrotic area is also improved. This study reveal the mechanism by which LncAABR07053481 inhibits hypoxia-induced apoptosis of BMSCs by regulating the miR-664-2-5p/ Notch1 pathway and its therapeutic effect on SANFH.
To assess the survival and prognostic significance of various demographic and radiographic parameters for conversion into total hip arthroplasty after treatment with a modified porous tantalum implant technology for early and intermediate stages of osteonecrosis of the femoral head (ONFH).This study included 45 patients (59 hips) with Steinberg Stage I-IV A ONFH undergoing progressively core decompression, impaction bone grafting of 5 mm-composite bone filling material and inserting of a porous tantalum implant. Weight-bearing was forbidden within the first 3 months after implants.A total of 57 hips (44 patients) were available during a mean follow-up period of 44.8 (11-62) months. Their mean age was 43 (21-70) years. The mean Harris hip score significantly improved from 59.93 ± 2.80 preoperative to 77.84 ± 2.95 at the last follow-up (P < 0.001). Overall, 11 hips (19.30%) were converted into total hip arthroplasty. The overall survival rate was 72.49% at 60 months postoperatively. The Cox proportional hazard model revealed that bone marrow edema was an independent prognostic factor related with a conversion into total hip arthroplasty.Higher survival rates may be obtained from modified tantalum implant technology for early and intermediate stages of ONFH. And prognosis was poor for patients of ONFH with bone marrow edema.
Background: Latest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function. Methods: Ninety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue. Results: BBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C ( P <0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly ( P <0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C ( P <0.05). Conclusion: Low-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal injury. Keywords: spinal injury, impact wave, VEGF, Flt-1, nerve protection
Oxidative stresss in the microenvironment surrounding lesions induces apoptosis of transplanted bone-marrow-derived mesenchymal stem cells (BMSCs). Hence, there is an urgent need for improving antioxidative-stress processes of transplanted BMSCs to further promote their survival. The present study reports the role and mechanism of Parkinson's disease protein 7 (PARK7) in enhancing antioxidative activity in BMSCs. We used a PARK7 lentivirus to transfect BMSCs to up- or downregulate PARK7, and then used H2 O2 to simulate oxidative stress in BMSCs in vitro. Overexpression of PARK7 effectively reduced reactive oxygen species and malondialdehyde, protected mitochondrial membrane potential, and resisted oxidative-stress-induced apoptosis of BMSCs, but the expression of PARK7 was downregulated, these results were reversed. At the same time, we also found that overexpression of PARK7 increased extracellular-regulated protein kinase 1/2 (ERK1/2) phosphorylation and nuclear translocation, as well as upregulated Elk1 phosphorylation and superoxide dismutase (SOD) expression. In contrast, when U0126 was used to block the ERK1/2 pathway, ERK1/2 and Elk1 phosphorylation levels were downregulated, ERK1/2 nuclear translocation and SOD content were significantly reduced, and PARK7-overexperssion-induced antioxidative activity was completely blocked. Collectively, our results suggest that PARK7 overexpression increased antioxidative-stress processes and survival of BMSCs subjected to H2 O2 via activating the ERK1/2 signaling pathway. Our findings may guide the development of a PARK7-specific strategy for improving the transplantation efficacy of BMSCs.
Treatment for osteonecrosis of the femoral head (ONFH) in young individuals remains controversial. We developed a lantern-shaped screw, which was designed to provide mechanical support for the femoral head to prevent its collapse, for the treatment of ONFH. The purpose of this study was to investigate the efficacy and safety of the lantern-shaped screw loaded with autologous bone for the treatment of pre-collapse stages of ONFH.Thirty-two patients were randomly divided into two groups: the lantern-shaped screw group (core decompression and lantern-shaped screw loaded with autogenous bone) and the control group (core decompression and autogenous bone graft). During 36 months follow-up after surgery, treatment results in patients were assessed by X-ray and computed tomography (CT) scanning as well as functional recovery Harris hip score (HHS).Successful clinical results were achieved in 15 of 16 hips (94%) in the lantern-shaped screw group compared with 10 of 16 hips (63%) in the control group (p = 0.0325). Successful radiological results were achieved in 14 of 16 hips (88%) in the lantern-shaped screw group compared with 8 of 16 hips (50%) in the control group (P = 0.0221).The lantern-shaped screw loaded with autologous bone for the treatment of pre-collapse stages of ONFH is effective and results in preventing progression of ONFH and reducing the risk of femoral head collapse.The trial registration number: ChiCTR-TRC-13004078 (retrospectively registered at 2013-11-28).
OBJECTIVE To compare clinical efficacy between anatomical locking plate (ALP) and ordinary steel plate (OSP) in treating closed calcaneal fractures with SandersⅡ and Ⅲ. METHODS From May 2016 to May 2018, 68 patients with closed Sanders typeⅡ and Ⅲ calcaneal fractures were retrospectively analyzed, and were divided into anatomical locking plate group (ALP group) and ordinary steel plate group (OSP group) according to two kinds of plate fixation, and 34 patients in each group. In ALP group, there were 21 males and 13 females aged from 20 to 63 years old with average of (35.16±8.45) years old; 14 patients were typeⅡand 20 patients were type Ⅲaccording to Sanders classification;treated with ALP. In OSP group, there were 20 males and 14 females aged from 19 to 63 years old with average of (35.05±8.39) years old;19 patients were typeⅡand 15 patients were type Ⅲ according to Sanders classification;treated with OSP. Operative time, intraoperative blood loss and complications between two groups were observed and compared;preoperative and postoperative Bohler angle and gissane angle were also compared;American Orthopaedic Foot & Ankle Society (AOFAS) ankle and hind foot scores, foot and ankle disability index (FADI) scores were applied to evaluate clinical effect. RESULTS All patients were followed up from 11 to 14 months with an average of (12.06±0.81) months. There were no statistical differences in opertive time, intraoperative blood loss, incision infection and refracture rate in complications between two groups (P>0.05);while there was significant difference in the number of screw loosening (P 0.05). CONCLUSION Compared with OSP, ALP in treating SandersⅡ and Ⅲ calcaneal fractures could achieve better therapeutic effect, avoid screw loosening, reduce complications, and improve limb function in further.
Abstract Oxidative stress damage is a common problem in bone marrow mesenchymal stem cell (BMSC) transplantation. Under stress conditions, the mitochondrial function of BMSCs is disrupted, which accelerates senescence and apoptosis of BMSCs, ultimately leading to poor efficacy. Therefore, improving mitochondrial function and enhancing the antioxidative stress capacity of BMSCs may be an effective way of improving the survival rate and curative effect of BMSCs. In the present study, we have confirmed that overexpression of nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) improves mitochondrial function and resistance to stress-induced apoptosis in BMSCs. We further revealed the mechanism of NMNAT3-mediated resistance to stress-induced apoptosis in BMSCs. We increased the level of nicotinamide adenine dinucleotide (NAD+) by overexpressing NMNAT3 in BMSCs and found that it could significantly increase the activity of silent mating type information regulation 2 homolog 3 (Sirt3) and significantly decrease the acetylation levels of Sirt3-dependent deacetylation-related proteins isocitrate dehydrogenase 2 (Idh2) and Forkhead-box protein O3a (FOXO3a). These findings show that NMNAT3 may increase the activity of Sirt3 by increasing NAD+ levels. Our results confirm that the NMNAT3-NAD+-Sirt3 axis is a potential mechanism for improving mitochondrial function and enhancing antioxidative stress capacity of BMSCs. In the present study, we take advantage of the role of NMNAT3 in inhibiting stress-induced apoptosis of BMSCs and provide new methods and ideas for breaking through the bottleneck of transplantation efficacy of BMSCs in the clinic.
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