Kota Miyoshi

Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family

Background Mutations in TRPV4, a gene that encodes a Ca2+ permeable non-selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. Objectives and methods To examine TRPV4 mutation spectrum and phenotype−genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. Results TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. Conclusion The TRPV4 mutation spectrum in MD and SMDK, which showed genotype−phenotype correlation and potential functional significance of mutations that are non-randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases.

Association Analysis of Single Nucleotide Polymorphisms in Cartilage‐Specific Collagen Genes With Knee and Hip Osteoarthritis in the Japanese Population

Osteoarthritis (OA) is one of the most common diseases in the elderly. Although its pathophysiology is complex and its molecular basis remains to be determined, much evidence suggests that OA has strong genetic determinants. To search for susceptibility loci of OA, we selected seven candidate genes encoding cartilage‐specific collagens (type II, IX, X, and XI collagens) and performed association analysis for OA using single nucleotide polymorphisms (SNPs) in the coding region of these genes. Four hundred seventeen OA samples and 280 control samples were collected from the Japanese population, and 12 SNPs were genotyped. Our studies have identified two susceptibility loci of OA: COL2A1 and COL9A3. An SNP in COL9A3 showed significant association with knee OA (p = 0.002, odds ratio [OR] = 1.48). Haplotype analysis showed significant association between a specific haplotype of COL2A1 and hip OA (p = 0.024; OR = 1.30). Further analysis of these two genes will shed light on the molecular mechanisms of OA.

Surgical treatment for atlantoaxial subluxation with myelopathy in spondyloepiphyseal dysplasia congenita.

Study Design. A retrospective review of 21 patients with spondyloepiphyseal dysplasia congenita (SEDC), including 7 operated patients for atlantoaxial subluxation. Objectives. To clarify the morphological findings of atlantoaxial subluxation in SEDC patients and to evaluate the operative procedures based on these image findings. Summary and Background Data. The presence of atlanto axial sublucation with hypoplasia of the odontoid and/or lax ligaments leads to myelopathy in patients with spondyloepiphyseal dysplasia congenita. Methods. We retropectively reviewed the physical and morphological findings on atlantoaxial images and the clinical findings of myelopathy in 21 patients with SEDC. Results. Myelopathy was found in 9 individuals with severe SEDC who presented with marked short stature and severe coxa vara; of these, 6 had gait disturbances. On the images of the 9 patients with myelopathy, the average sagittal canal diameter (SCD) at the level of the atlas was only 9.2 mm (range, 7–12 mm) with progressive atlantoaxial subluxation. The average atlantodental interval (ADI) was 3.5 mm (range, 2–6 mm) in the presence of a sagittal atlas diameter (SAD) of less than 27.1 mm (range, 22–36 mm). Surgery was performed for 6 of the patients with myelopathy. Since their SADs were small, and the average SCD, at 9.9 mm (8–14 mm), was narrow even at the position of extension (the position of reduction for atlantoaxial subluxation), C1 laminectomy was needed for all these patients, and occipital-cervical posterior fusion was performed. Stability was satisfactory in all cases and the operative outcome for myelopathy was excellent for 1 case, fine for 4, and fair for 2. Conclusion. A small SAD may limit the effectiveness of reducing atlantoaxial subluxation. Persistent narrowing of the SCD may require concomitant C1 laminectomy and occipital-cervical fusion.

Expansive cervical laminoplasties – observations on comparative changes in spinous process lengths following longitudinal laminal divisions using autogenous bone or hydroxyapatite spacers

Expansive laminoplasty is devised to preserve the posterior structures, including the original length of the spinous process which anchors the nucheal muscles, in order to prevent the postoperative development of instability and cervical kyphosis due to structural loss and poor tone of the nucheal muscles, which can result in late neurological regression after laminectomy for cervical myelopathy.We retrospectively compared the length of the spinous process at the time of follow-up with that within 3 months postoperatively using CT images. The shortening was observed in 80% of 60 spinous processes in 13 patients, where a hydroxyapatite (HA) block was used as a spacer placed between the two sides of the split spinous process. The incidence was 9% of 22 spinous processes in six patients where auto bone graft (ABG) was used as a spacer, and the difference was significant (P<0.01, Chi-square test).Although the usage of HA has the advantage of being less invasive than ABG, it may jeopardize the biomechanical function of nucheal muscles due to reduction in the original length of the spinous process.

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.

AbstractOsteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population.

Removal of enterogenous cyst of the cervical spine through anterior approach.

Enterogenous cyst is a cause of spinal cord compression. The cyst has been treated surgically through a posterior approach in spite of the location ventral to the spinal cord. We saw two patients who had recurrence at 1 and 3 years after partial removal through this approach. We removed the cyst at the level of the cervical spine in four patients totally or subtotally through an anterior approach. All patients improved neurologically, and there were no signs or symptoms of recurrence at follow-up of from 2 to 13 years (average, 7 years 3 months). It is reasonable to approach the cyst located ventrally to the spinal cord through the anterior route, where the relationship between the cyst wall and the spinal cord can be viewed directly.

Combined Video-Assisted Thoracic Surgery and Posterior Spinal Surgery for the Treatment of Dumbbell Tumor of the First Thoracic Nerve Root.

Although several cases of a dumbbell tumor of thoracic nerve roots have been reported, reports on the surgical procedures for a dumbbell tumor of the first thoracic (T1) nerve root are rare. Surgeons should be cautious, especially when performing a surgical procedure for a dumbbell tumor of the T1 nerve root because the tumor is anatomically located adjacent to important organs and because the T1 nerve root composes the lower trunk of the brachial plexus with the eighth cervical nerve root. We present cases with dumbbell tumors of the T1 nerve root that were treated with combined surgical treatment to remove the tumor. We first performed video-assisted thoracic surgery (VATS) to release the organs anteriorly and then performed posterior spinal surgery in the prone position. The combined VATS and posterior spinal surgery may become a standard surgical procedure for the treatment of dumbbell tumors of the T1 nerve root.

Risk factors for incidental durotomy during posterior open spine surgery for degenerative diseases in adults: A multicenter observational study

Incidental durotomy (ID) is a common intraoperative complication of spine surgery. It can lead to persistent cerebrospinal fluid leakage, which may cause serious complications, including severe headache, pseudomeningocele formation, nerve root entrapment, and intracranial hemorrhage. As a result, it contributes to higher healthcare costs and poor patient outcomes. The purpose of this study was to clarify the independent risk factors that can cause ID during posterior open spine surgery for degenerative diseases in adults. We conducted a prospective multicenter study of adult patients who underwent posterior open spine surgery for degenerative diseases at 10 participating hospitals from July 2010 to June 2013. A total of 4,652 consecutive patients were enrolled. We evaluated potential risk factors, including age, sex, body mass index, American Society of Anesthesiologists physical status classification, the presence of diabetes mellitus, the use of hemodialysis, smoking status, steroid intake, location of the surgery, type of operative procedure, and past surgical history in the operated area. A multivariate logistic regression analysis was performed to identify the risk factors associated with ID. The incidence of ID was 8.2% (380/4,652). Corrective vertebral osteotomy and revision surgery were identified as independent risk factors for ID, while cervical surgery and discectomy were identified as factors that independently protected against ID during posterior open spine surgery for degenerative diseases in adults. Therefore, we identified 2 independent risk factors for and 2 protective factors against ID. These results may contribute to making surgeons aware of the risk factors for ID and can be used to counsel patients on the risks and complications associated with open spine surgery.

Risk factors for surgical site infection after lumbar laminectomy and/or discectomy for degenerative diseases in adults: A prospective multicenter surveillance study with registry of 4027 cases

Surgical site infection (SSI) is a significant complication after spinal surgery and is associated with increased hospital length of stay, high healthcare costs, and poor patient outcomes. Accurate identification of risk factors is essential to develop strategies to prevent wound infections. The aim of this prospective multicenter study was to determine the independent factors associated with SSI in posterior lumbar surgeries without fusion (laminectomy and/or herniotomy) for degenerative diseases in adult patients. From July 2010 to June 2014, we conducted a prospective multicenter surveillance study in adult patients who developed SSI after undergoing lumbar laminectomy and/or discectomy in ten participating hospitals. Detailed patient and operative characteristics were prospectively recorded using a standardized data collection format. SSI was based on the Centers for Disease Control and Prevention definition. A total of 4027 consecutive adult patients were enrolled, of which 26 (0.65%) developed postoperative SSI. Multivariate regression analysis indicated two independent factors. An operating time >2 h (P = 0.0095) was a statistically significant independent risk factor, whereas endoscopic tubular surgery (P = 0.040) was a significant independent protective factor. Identification of these associated factors may contribute to surgeons’ awareness of the risk factors for SSI and could help counsel the patients on the risks associated with lumbar laminectomy and/or discectomy. Furthermore, this study’s findings could be used to develop protocols to decrease SSI risk. To the best of our knowledge, this is the first prospective multicenter study that identified endoscopic tubular surgery as an independent protective factor against SSI after lumbar posterior surgery without fusion.

The effect of the “One Stretch” exercise on the improvement of low back pain in Japanese nurses: a large-scale, randomized, controlled trial

Abstract Objectives: To evaluate the ‘One Stretch’ exercise’s effect on improvements in low back pain (LBP), psychological factors, and fear avoidance in a large number of nurses. Methods: Between July 2015 and June 2016, we performed a prospective, randomized, parallel-group, multi-center study with central evaluations. Eligible patients were randomly assigned (1:1:1 ratio) to either the control group (Group A) or an intervention group (Group B: 30-min seminar about the ‘One Stretch’ exercise, Group C: B + physical and psychological approaches to LBP treatment). The primary outcome was subjective improvement from baseline to 6 months (improved/unchanged/worsened) and overall exercise habits (good/poor). Results: There were 4767 participants: 1799, 1430, and 1548 in Groups A, B, and C, respectively. We collected data on 3439 participants (949, 706, and 751 in Groups A, B, and C, respectively) at the 6-month follow-up. The improvement rates in Groups A, B, and C were 13.3%, 23.5%, and 22.6%, respectively. The worsened pain rates were 13.0%, 9.6%, and 8.1%, which decreased as the intervention degree increased (the Cochran–Armitage trend test: p < .0001). In Groups A, B, and C, 15.6%, 64.9%, 48.8% of the patients, respectively, exhibited exercise habits. Conclusion: The ‘One Stretch’ exercise is useful for improving LBP.