Imaging and histological evaluation of the long head of the biceps tendon in the presence of different types of rotator cuff tears.

BACKGROUND: A comparison of changes in the long head of the biceps tendon for different types of rotator cuff tears has not been previously performed. Furthermore, the correlation between the thickening and degeneration of the long head of the biceps tendon and the cause of these changes have not been fully clarified. We evaluated the relationship between degenerative changes in the long head of the biceps tendon and rotator cuff tears in a rat model using imaging and histology. METHODS: Ninety-six 12-week-old Sprague-Dawley rats were divided into anterior (subscapularis tear), anterosuperior (subscapularis, supraspinatus, and infraspinatus tears), superior (supraspinatus and infraspinatus tears), and control groups. The long head of the biceps tendon was harvested at 4 or 12 weeks postoperatively. The cross-sectional areas of the intra- and extra-capsular components of the tendon were measured using micro-computed tomography, and the affected/normal ratio of the cross-sectional area was calculated. Masson's trichrome staining and Alcian blue staining were performed for histologic analysis, with degenerative changes described using the modified Bonar scale. The correlation between the affected/normal ratio and Bonar scores was evaluated. RESULTS: The affected/normal ratio was higher for the anterior and anterosuperior groups than for the control group at 4 and 12 weeks. The ratio increased for the intra-articular portion in the superior group and for both the intra- and extra-articular portions in the anterior and anterosuperior groups. Degeneration considerably progressed in the anterior and anterosuperior groups compared with the control group from weeks 4 to 12 and was greater in the intra- than in the extra-articular portion. The ratio correlated with extracellular matrix score. CONCLUSIONS: Subscapularis tears were associated with progressive thickening and degeneration of the long head of the biceps tendon at 4 and 12 weeks postoperatively, which was more significant in the intra- than in the extra-articular portion. Histologic evaluation indicated that the extracellular matrix likely caused these degenerative changes.

Tumor necrosis factor receptor-1 is selectively sequestered into Schwann cell extracellular vesicles where it functions as a TNFα decoy.

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell-cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor-1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Although TNFR2 was robustly expressed by SCs in culture, TNFR2 was excluded from SC EVs. SC EV TNFR1 bound TNFα, decreasing the concentration of free TNFα available to bind to cells and thus served as a TNFα decoy. SC EV TNFR1 significantly inhibited TNFα-induced p38 MAPK phosphorylation in cultured SCs. When TNFR1 was proteolytically removed from SC EVs using tumor necrosis factor-α converting enzyme (TACE) or neutralized with antibody, the ability of TNFα to activate p38 MAPK in the presence of these EVs was restored. As further evidence of its decoy activity, SC EV TNFR1 modified TNFα activities in vitro including: (1) regulation of expression of other cytokines; (2) effects on SC morphology; and (3) effects on SC viability. SC EVs also modified the effects of TNFα on sciatic nerve morphology and neuropathic pain-related behavior in vivo. By sequestering TNFR1 in EVs, SCs may buffer against the potentially toxic effects of TNFα. SC EVs provide a novel mechanism for the spatial and temporal regulation of neuro-inflammation.

Frozen vein wrapping for chronic nerve constriction injury reduces sciatic nerve allodynia in a rat model.

BACKGROUND: Autologous vein wrapping (VW) is used in the treatment of recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, use of autologous veins is limited by the inability to obtain longer veins of sufficient length for larger sites. Frozen allograft tissue has several advantages, including its availability for large grafts, avoidance of donor-site morbidity, and shorter operation time. Here, we investigated the effect of frozen vein wrapping (FVW) in Wistar rats as a model of sciatic nerve injury. RESULTS: The rats were grouped by treatment as (i) untreated after chronic constriction injury surgery (CCI; control group), (ii) treated with vein wrapping using freshly isolated vein (VW), and (iii) treated with vein wrapping using frozen vein (FVW). Mechanical allodynia was assessed with von Frey filaments on postoperative days (PODs) 1, 3, 5, 7, and 14. Gene expression of HO-1 was evaluated by quantitative polymerase chain reaction (qPCR). The response of heme oxygenase-1 gene, Hmox-1, expression to VW and FVW was assessed by RT-PCR. Both VW and FVW significantly increased withdrawal threshold levels compared to the untreated control group on POD 1, 3, and 5. Both VW and FVW also showed increased HO-1 expression compared to the CCI group. CONCLUSIONS: FVW increased the withdrawal threshold similar to VW in a rat CCI model for short periods. Frozen vein wrapping using vein allograft without donor site morbidity may be an alternative therapeutic option.

Effect of arthroscopic subacromial decompression during arthroscopic repair of small to medium-sized rotator cuff tears.

Background: Although arthroscopic subacromial decompression (ASD) is a commonly used procedure during arthroscopic rotator cuff repair (ARCR), the effect of ASD on the clinical outcomes for ARCR is controversial. The purpose of this study was to compare the clinical outcomes of ARCR with or without ASD. Methods: Patients (n = 315 with 320 shoulders) who underwent ARCR for small to medium-sized rotator cuff tears were followed for at least 24 months. ARCR was performed with ASD (180 shoulders, group A) or without ASD (140 shoulders, group N). There were no significant differences in patient demographics, including mean age and mean follow-up time. Rotator cuff repair was performed using the suture-bridge technique in all shoulders, and all patients were treated using the same rehabilitation protocol after surgery. University of California at Los Angeles score, Constant score, re-tear rates, revision surgery rates, and operating time were compared between groups. Re-tear was defined as Sugaya classification Types 4 and 5 using postoperative magnetic resonance imaging at more than 12 months. Results: There was no statistically significant difference in clinical outcomes before and after ARCR between groups. However, the University of California at Los Angeles scores and Constant scores significantly improved in both groups after surgery (P < .001). Furthermore, there was no major difference in the re-tear rates between groups A (7/180 shoulders, 3.9%) and N (11/140 shoulders, 7.9%) (P = .146). Revision surgeries were performed on 3/180 shoulders (1.7%) in group A (due to postoperative deep infection in one shoulder and revision ARCR for re-tear in two shoulders). No revisions surgeries were needed in group N patients (P = .259). The mean surgical time for group A was 62.0 ± 27.0 minutes (29-138 min.) and 52.4 ± 26.1 minutes (17-124 min.) for group N (P = .007). Conclusion: These results suggest that ASD has a limited effect on clinical outcomes of ARCR for small to medium-sized rotator cuff tears.

Evaluation of articular changes using a rat mono-iodoacetate-induced shoulder arthritis model by histology and radiology.

The rat mono-iodoacetate (MIA) arthritis model has been used in studies on the hip, knee, and ankle joints. Few studies have explored its utility in shoulder arthritis research, and none have evaluated the effects of time and different MIA doses on arthritis progression. Therefore, we developed a rat MIA shoulder arthritis model to evaluate articular changes through radiological and histological analyses. Sprague-Dawley rats (n = 108) were equally divided into groups that were intra-articularly injected with 0.5 mg of MIA (in 50 µL of purified water), 2.0 mg of MIA (in 50 µL of purified water), or purified water (50 µL; sham group). Throughout the study period, 18 rats (six per group) were evaluated by computed tomography and assessed using the Larsen's classification system; 90 rats were further evaluated histologically using the Osteoarthritis Research Society International scoring system. Computed tomography revealed that the groups injected with MIA developed arthritis and osteophytes 14 days after injection, which progressed temporally. The Larsen's grades worsened over time; at all time points, the scores were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Furthermore, concurrent with the worsening Larsen's grades, the Osteoarthritis Research Society International scores also significantly increased over time; at all time points, they were higher in the group injected with 2.0 mg of MIA than in the group injected with 0.5 mg of MIA. Our rat MIA shoulder arthritis model revealed radiologically and histologically confirmed temporal and MIA dose-dependent arthritic changes.

Nerve decompression surgery suppresses TNF-ɑ expression and T cell infiltration in a rat sciatic nerve chronic constriction injury model.

Decompression surgery (DS) is a standard treatment for chronic nerve compression injuries; however, the mechanisms underlying its effects remain unclear. Here, we investigated the effects of DS on messenger RNA (mRNA) expression of tumor necrosis factor-α (TNF-α) and T cell recruitment in a rat sciatic nerve (SN) chronic constriction injury (CCI) model. Male Wistar rats were subjected to CCI to establish a model of SN injury (CCI group). DS, in which all ligatures were removed, was performed 3 days after CCI surgery (CCI + dec group). Mechanical sensitivity was assessed using the von Frey test 3, 7, and 14 days after the CCI surgery. Gene expression of Tnfa, Cd3, Cxcl10, and immunolocalization of TNF-α and the pan T cell marker, CD3, was evaluated using quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. In addition, the effects of TNF-α on Cxcl10 expression and CXCL10 protein production were evaluated using qPCR and enzyme-linked immunosorbent assay in SN cell culture. Rats that received DS had significantly higher withdrawal threshold levels than those in the CCI group. In addition, Tnfa, Cd3, and Cxcl10 mRNA expression increased following CCI. DS suppressed this elevated expression, with the CCI + dec group showing significantly reduced expression levels compared to the CCI group. Furthermore, TNF-α induced Cxcl10 expression and CXCL10 protein production in SN cell culture. Therefore, DS reduced TNF-α expression and T cell recruitment in the rat SN CCI model. These observations may partly explain the mechanism underlying the therapeutic effects of DS.

Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy.

STUDY DESIGN: Retrospective observational study. PURPOSE: We investigated the correlation between T2 relaxation times and clinical symptoms in patients with cervical radiculopathy caused by cervical disk herniation. OVERVIEW OF LITERATURE: There are currently no imaging modalities that can assess the affected cervical nerve roots quantitatively. METHODS: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. RESULTS: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. CONCLUSIONS: In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Giant Protruding High-Grade Undifferentiated Pleomorphic Sarcoma Arising in a Keloid Scar on the Abdominal Wall.

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, aggressive, soft tissue sarcoma that is often fatal. Although there are reports describing associations of sarcoma and skin lesions such as burns, radiation, and trauma, to our knowledge, UPS development in a keloid scar has not been reported. Herein, we present the case of a 76-year-old woman who had undergone surgery for endometrial cancer, 5 years before. She presented with a protruding lesion that was continuous to a keloid scar on the abdominal wall. The tumor appeared clinically malignant as it was protruding and doubled in size within three weeks, reaching approximately 6 × 6 × 2 cm. Since the tumor was diagnosed as UPS after pathological evaluation by needle biopsy, wide resection was performed. Intraoperatively, the tumor was apparently continuous to the keloid, protruding and pedunculated outside the body, and had not invaded the abdominal cavity. Histopathological examination of the resected tumor showed evidence of UPS and no suspicion of metastasis of endometrial cancer. No recurrence, metastases, or other complications were noted 6 months after surgery. The current case study reminds us that keloids may cause high-grade sarcoma such as UPS, and careful follow-up is required.

Successful Treatment of a Massive Desmoplastic Fibroma of the Ilium without Surgery: A Case Report with Long-Term Follow-Up.

Desmoplastic fibroma of the bone (DFB) is a notably rare, lytic, locally aggressive but nonmetastatic, primary benign bone tumor in patients less than 30 years old. As the recommended primary treatment for DFB, wide resection is preferred to curettage from the perspective of recurrence but wide resection of DFB in the pelvis such as in the acetabulum could result in greater functional loss, suggesting the need for conservative treatments. However, there is no report on long-term follow-up following conservative treatment for DFB. The present case involved a 21-year-old woman with right hip pain. Radiological evaluation revealed a massive lesion throughout the right ilium and acetabulum with partial osteolysis, cortical destruction, marginal sclerosis, slight pseudotrabeculation, and bone expansion. Open biopsy from the ilium showed the proliferation of spindle cells in an abundant collagenous matrix without atypia and mitosis, suggesting a diagnosis of DFB. Conservative treatment was selected considering the risk of greater functional loss following wide ilium resection. An evaluation 10 years after follow-up showed a partially sclerotic lesion of the ilium and the absence of pain. The current case demonstrates that conservative therapy may be effective even in some cases of aggressive DFB.

Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome with Purely Osteolytic, Not Osteosclerotic, Lesions Mimicking a Malignant Tumor.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare inflammatory disorder with multiple phenotypes. The syndrome has identifiable radiologic characteristics that are the most important when making a diagnosis. X-rays of cases diagnosed with SAPHO syndrome reveal sclerotic lesions or mixed lytic and sclerotic lesions. Pure osteolytic lesions in SAPHO syndrome are rare, and to the best of our knowledge, no study has reported the radiologic change of purely osteolytic lesions to osteosclerotic lesions over time. Herein, we report on the case of a woman experiencing severe left thigh acute pain and having a medical history of palmoplantar pustulosis. Although SAPHO syndrome was suspected because of palmoplantar pustulosis, based on radiologic findings, bone metastasis of a malignant tumor or chronic bacterial osteomyelitis owing to a purely osteolytic lesion was suspected. However, needle biopsy revealed no malignancy and bacterial culture was negative, thus suggesting SAPHO syndrome. Nonsteroidal anti-inflammatory drugs, bisphosphonates, and corticosteroids were administered, which improved the left thigh pain. Furthermore, the radiologic change of osteolytic lesions to osteosclerotic lesions over time was confirmed, leading to the diagnosis of SAPHO syndrome. Our case demonstrates that knowledge of atypical radiologic findings is necessary to diagnose initial SAPHO syndrome.

Successful Neurological Recovery with Multimodality Therapy without Surgery for Spinal Metastases from Advanced Gastric Cancer.

Advanced gastric cancer with bone metastasis has a very poor prognosis with short median survival. To the best of our knowledge, no reports in literature have described extensive recovery of paralysis with multimodality treatment without surgery in these cases. This report describes the case of a 52-year-old severely paralyzed female patient with spinal metastasis from advanced gastric cancer. She was inoperable, owing to a large thrombus in the inferior vena cava; alternative multimodality treatments, including chemotherapy and radiotherapy, were administered. The paralysis and the bladder and rectal dysfunction improved considerably. In addition, the performance status (PS) and Frankel grade also improved dramatically, from 4 to 1 and grade B to D, respectively. At 1 year after initiation of treatment, she is ambulatory. Patients with poor PS are often offered palliative therapy. However, this case demonstrates that poor PS solely due to paralysis from spinal metastasis may necessitate multimodality treatment instead of palliative care.

Freeze-Dried Platelet-Rich Plasma Induces Osteoblast Proliferation via Platelet-Derived Growth Factor Receptor-Mediated Signal Transduction.

STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the in vitro pharmacological activity of growth factors (GFs) in freeze-dried platelet-rich plasma (FD-PRP) after storage for 4 weeks. OVERVIEW OF LITERATURE: Freshly prepared PRP is a rich source of many GFs. We reported that FD-PRP stored for 8 weeks accelerated bone union in a rat posterolateral fusion model equally well as fresh-PRP. However, the pharmacological activity of FD-PRP after longterm storage has not been shown in vitro. METHODS: Immediately after preparation, as well as 4 weeks after freeze-dried storage, the platelet count was measured. Human osteoblasts were treated with fresh-PRP and FD-PRP, respectively. Western blotting was used to assess the phosphorylation of the platelet-derived growth factor (PDGF) receptor (PDGFR) and its downstream target, extracellular signal-regulated kinase (ERK). The proliferation rates of osteoblasts were investigated by immunocytochemistry and MTT cell viability assays. Furthermore, we used western blotting to evaluate the effect of PDGFR knockdown on the phosphorylation of ERK stimulated with fresh-PRP and FD-PRP. RESULTS: Platelet counts in both the fresh-PRP and FD-PRP samples were approximately 10-fold higher than in peripheral blood samples. The phosphorylation and activation of the PDGFR and ERK were evenly induced by fresh-PRP and FD-PRP stimulation. Both freshPRP and FD-PRP significantly induced osteoblast proliferation in MTT cell viability assays. Furthermore, osteoblast PDGFR knockdown attenuated the downstream ERK activation by fresh PRP and FD-PRP. CONCLUSIONS: We demonstrated the pharmacological activity of PDGF in FD-PRP in vitro after 4 weeks of storage.

Pilot study of oblique lumbar interbody fusion using mobile percutaneous pedicle screw and validation by a three-dimensional finite element assessment.

The purpose of this study was to try oblique lateral interbody fusion (OLIF) using percutaneous pedicle screws (PPS) with mobility. Twelve patients who underwent single-level OLIF were observed for at least one year. These included 6 patients with conventional PPS (rigid group), and 6 with movable PPS (semi-rigid group). Mobile PPS used cosmicMIA, which is a load sharing system. The anterior and posterior disc height, screw loosening and bone healing period, and implant failure were evaluated at final observation by CT. Moreover, the stress on the vertebral body-cage, on the vertebral body-screw/rod and on the bone around the screw was estimated using a three-dimensional finite element assessment in both groups. There was no significant difference in surgical time, amount of bleeding, JOA score, or low back pain VAS between groups. There were no differences between groups in anterior and posterior disc height, screw loosening, and implant failure at final observation. The bone healing period was significantly shorter in the semi-rigid screw group (18.3 months vs 4.8 months, p = 0.01). The finite element analysis showed that the lower stress on the rod/screw would contribute to fewer implant fractures and that lower stress on the bone around the screw would reduce screw loosening, and that higher compressive force on the cage would promotes bone healing. OLIF combined with a movable screw accelerated bone healing by nearly 75%. We conclude that mobile PPS in combination with OLIF promotes bone healing and can be a better vertebral fusion technique.

Simultaneous MR neurography and apparent T2 mapping of cervical nerve roots before microendoscopic surgery to treat patient with radiculopathy due to cervical disc herniation: Preliminary results.

There is no imaging modality to quantitatively evaluate compressed cervical nerve roots in cervical radiculopathy. Here we sought to evaluate the usefulness of simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation-enhancement imaging (SHINKEI-Quant) to evaluate compressed nerves quantitatively in patients with cervical radiculopathy due to cervical disc hernia before microendoscopic surgery. One patient with cervical radiculopathy due to cervical disc hernia before microendoscopic surgery and 5 healthy subjects underwent simultaneous apparent T2 mapping and neurography with SHINKEI-Quant. The patient was a 49-year-old man with severe right upper arm pain and numbness. Based on MRI images, we suspected right C7 radiculopathy due to C6-7 cervical disc hernia. The T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus bilaterally at C5-C8 were measured. We observed no significant differences in T2 relaxation times between the nerve roots on the left and right at each spinal level with values in healthy subjects. In our patient, neurography revealed swelling of the right C7 nerve, and a prolonged T2 relaxation time compared with that of the contralateral, unaffected C7 nerve. We performed microendoscopic surgery and the symptoms improved. We were able to evaluate the injured nerve root quantitatively in a patient with cervical radiculopathy using the SHINKEI-Quant technique, being the first study to our knowledge to show the usefulness of this technique to evaluate cervical radiculopathy quantitatively before microendoscopic surgery.

Diagnosis of lumbar radiculopathy using simultaneous MR neurography and apparent T2 mapping.

We sought to assess the utility of simultaneous apparent T2 mapping and neurography with the nerve-sheath signal increased by inked rest-tissue rapid acquisition of relaxation-enhancement imaging (SHINKEI-Quant) for the quantitative evaluation of compressed nerves in patients with lumbar radiculopathy. Thirty-two patients with lumbar radiculopathy and 5 healthy subjects underwent simultaneous apparent T2 mapping and neurography with SHINKEI-Quant. Regions of interest (ROIs) were placed in the lumbar dorsal root ganglia (DRG) and the spinal nerves distal to the lumbar nerves bilaterally at L4-S1. The T2 relaxation times were measured on the affected and unaffected sides. The T2 ratio was calculated as the affected side/unaffected side. Pearson correlation coefficients were calculated to determine the correlation between the T2 relaxation times or T2 ratio and clinical symptoms. An ROC curve was used to examine the diagnostic accuracy and threshold of the T2 relaxation times and T2 ratio. We observed no significant differences in the T2 relaxation times between the nerve roots on the left and right at each spinal level in healthy subjects. In patients, lumbar neurography revealed swelling of the involved nerve, and prolonged T2 relaxation times compared with that of the contralateral nerve. The T2 ratio correlated with leg pain. The ROC analysis revealed that the T2 relaxation time threshold was 127 ms and the T2 ratio threshold was 1.07. To our knowledge, this is the first study to show the utility of SHINKEI-Quant for the quantitative evaluation of lumbar radiculopathy.

Giant Protruding Nodular Fasciitis of the Anterior Chest Wall Clinically Mimicking a Soft Tissue Sarcoma.

Nodular fasciitis (NF) is a benign reactive proliferation of myofibroblasts that predominantly occurs subcutaneously. Commonly, it presents as a rapidly growing swelling in 4-8 weeks. NF mostly occurs in adults aged 20-50 years and usually has a diameter < 3-4 cm. Giant NF with a diameter > 4 cm is rare. Owing to its rapidly growing nature, a precise clinical diagnosis is difficult; it is frequently misdiagnosed as an aggressive or malignant tumor. Herein, we present the case of a 15-year-old male who presented with a large protruding mass on the anterior chest wall. The tumor appeared clinically malignant as it was protruding and had doubled in size within a few weeks, reaching approximately 8 × 6 cm. Furthermore, the tumor separated and fell off spontaneously due to its large size. As the remaining tumor continued to grow rapidly, surgery was performed. Following wide tumor resection, no recurrence, metastases, or other complications were noted 1 year postsurgery. NF was diagnosed after pathological evaluation, including immunohistochemical analysis, molecular genetic testing, and cytogenetic testing via fluorescence in situ hybridization analysis. Knowledge of the atypical clinical course and a combination of histopathological examinations are necessary to accurately diagnose NF.

Wrapping With Basic Fibroblast Growth Factor-Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia.

Autologous vein wrapping is used to treat recurrent chronic constriction neuropathy and traumatic peripheral nerve injury. However, its use is restricted due to the inability to obtain sufficiently long veins for larger grafts. We previously reported that vein-derived basic fibroblast growth factor (bFGF) promotes heme oxygenase-1 (HO-1), which reduces allodynia via its anti-inflammatory properties. To mimic vein wrapping, we developed a collagen sheet impregnated with bFGF. Chronic constriction injury (CCI) was induced in male Wistar rats as a model of sciatic nerve injury, and the rats were divided into three groups: (i) untreated after CCI surgery (control group), (ii) treated with a collagen sheet wrap impregnated with phosphate-buffered saline (PBS/CS group), and (iii) treated with a collagen sheet wrap impregnated with bFGF (bFGF/CS group). Pain behavior (von Frey test) was evaluated on postoperative days (PODs) 1, 5, 7, and 14. Quantitative polymerase chain reaction was conducted on sciatic nerve RNA to quantify HO-1 gene, Hmox1, expression. Enzyme-linked immunosorbent assay were used to determine HO-1 protein levels on POD 1. von Frey testing showed significantly greater pain hypersensitivity in the control and PBS/CS groups than the bFGF/CS group. In the bFGF/CS group, Hmox1 messenger RNA and HO-1 protein levels were significantly increased in the sciatic nerve compared with the control and PBS/CS groups on PODs 1 and 5 and POD 1, respectively. The bFGF/CS group showed decreased allodynia and HO-1 induction, as observed with vein wrapping. Therefore, local application of bFGF may be an alternative treatment strategy for compressive neuropathy and peripheral nerve trauma in clinical settings. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2258-2263, 2019.

Reduced leg muscle mass and lower grip strength in women are associated with osteoporotic vertebral compression fractures.

Lower limb muscle mass and grip loss may be risk factors for vertebral compression fractures in women. PURPOSE: We examined the relationship between bone mineral density, bone strength, skeletal muscle mass, grip strength, and skin autofluorescence (SAF) in women with osteoporotic vertebral compression fractures (VCF). METHODS: A total of 1039 women (mean age 73.3 years) were included in our study. These included 222 cases of VCF (mean 77.8 years) and 817 controls (mean 72.0 years). Lumbar and femur BMD were measured for all participants using dual-energy X-ray absorptiometry (DXA). Bone strength surrogates, such as cross-sectional area (CSA) of the proximal femur, were evaluated using Advanced Hip Assessment software. SAF was measured with an autofluorescence reader. We used a bioelectrical impedance analyzer (BIA) to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m))2. We measured bone density, geometric parameters related to bone strength, skeletal muscle mass, grip strength, and SAF in both groups. We also examined factors related to vertebral fracture using multiple logistic regression analysis. RESULTS: Women with vertebral fractures had lower SMI (5.55 vs 5.76 kg/m2, p = 0.0006), smaller femoral cross-sectional area (97.20 vs 100.09, p = 0.014), lower grip strength (16.81 vs 19.16 kg, p < 0.0001), and increased skin autofluorescence (2.38 vs 2.25, p = 0.0002) compared to women without fractures. The prevalence of sarcopenia (SMI < 5.75) was 63.51% in VCF subjects and 52.02% in controls, revealing a high prevalence in VCF (p = 0.002). Skeletal muscle mass and grip strength were not significantly different between patients with acute and old VCF, suggesting that low skeletal muscle mass and muscle weakness may exist before fracture. From the multiple logistic regression analysis, lower femoral density (p = 0.0021), CSA (p = 0.0166), leg muscle mass (p = 0.0127), and left arm grip strength (p = 0.0255) were risk factors for vertebral compression fractures; all were negatively correlated with increased vertebral fractures. CONCLUSIONS: Lower limb muscle mass and grip loss may be closely related to the onset of vertebral compression fracture.

Vein wrapping facilitates basic fibroblast growth factor-induced heme oxygenase-1 expression following chronic nerve constriction injury.

The clinical efficacy of autologous vein wrapping for recurrent compressive neuropathy has been demonstrated; however, the underlying mechanisms of this technique remain unclear. Rats were divided into chronic constriction injury (CCI) and CCI + vein wrapping (CCI + VW) groups. Mechanical allodynia was evaluated using von Frey filaments. To identify the neuroprotective factors released from veins, basic fibroblast growth factor (bFGF) mRNA expression in veins was compared to that in the sciatic nerve. The response of heme oxygenase-1 (HO-1) expression to vein wrapping was evaluated by RT-PCR and enzyme-linked immunosorbent assays. The effects of exogenous bFGF on HO-1 expression were evaluated using a sciatic nerve cell culture. Vein wrapping significantly increased the withdraw threshold levels compared to the untreated CCI group. bFGF mRNA expression in veins was higher than that in untreated sciatic nerves. HO-1 mRNA expression was induced at higher levels in sciatic nerve cells in the presence of exogenous bFGF compared to untreated control cells. HO-1 mRNA and protein expression in the sciatic nerve were also higher in the CCI + VW group compared with the CCI group. Our results suggest that vein-derived bFGF contributes to the therapeutic benefit of vein wrapping through the induction of HO-1 in the sciatic nerve. Vein wrapping is a useful technique for reducing neuropathic pain. Further understanding of the neurotrophic factors released from veins may help to optimize current procedures for treating recurrent compressive neuropathy and traumatic peripheral nerve injury, and lead to the development of new therapeutic methods using recombinant neurotrophic factors. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:898-905, 2018.

Vein wrapping promotes M2 macrophage polarization in a rat chronic constriction injury model.

Although the therapeutic potential of vein wrapping (VW) for recurrent compressive neuropathy has been widely reported, the mechanisms underlying this technique have not been characterized. M2 macrophages induced by interleukin-4 (IL-4) or interleukin-10 (IL-10) have an anti-inflammatory function and play an important role in peripheral nerve repair. To evaluate whether VW promotes M2 polarization, we divided chronic constriction injury (CCI) rats into untreated and VW (CCI + VW)-treated groups. Pain withdrawal thresholds in both groups were evaluated using von Frey filaments. Expression of the anti-inflammatory cytokines IL-4 and IL-10 in vein and nerve were quantified using real time polymerase chain reaction (RT-PCR), and expression of the anti-inflammatory M2 macrophage markers CD206 and arginase-1 (Arg1) after VW was assessed by RT-PCR and immunohistochemistry. To evaluate the effect of exogenous IL-4 or IL-10 on M2 macrophage-marker expression, CD11b-positive macrophages isolated from sciatic nerve were stimulated with recombinant IL-4 and IL-10. VW significantly increased the pain withdrawal threshold. IL-4 and IL-10 mRNA expression was higher in veins than in the sciatic nerve. VW significantly increased CD206 and Arg1 mRNA expression compared to the CCI group. The number of CD206- and Arg1-immunoreactive cells in nerve bundles was twofold higher in the CCI + VW than CCI group. Application of exogenous IL-4 doubled CD206 and Arg1 mRNA expression in CD11b-positive macrophages. These results show that vein-derived IL-4 potentiates the benefit of VW through the activation of M2 macrophages in the sciatic nerve. Our results may help to optimize current procedures for treating recurrent compressive neuropathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.