Publications by authors named "Koichi Murata"

163 Publications

Chondrosarcoma Arising from the Posterior Iliac Crest Extending into the Spinal Canal.

Case Rep Orthop 2021 17;2021:5510075. Epub 2021 Jul 17.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan.

Chondrosarcoma is a malignant tumor characterized by the production of a cartilage matrix. Extension into the spinal canal from the extracannular space is seen mainly for neurogenic tumors, but it is rare in nonneurogenic tumors. A 75-year-old woman suffered from sciatic pain and numbness in her lower left extremity. The diagnosis was of a low-grade conventional chondrosarcoma, which originated from the posterior ilium with an intraspinal extension at the level of the sacrum, compressing the cauda equina. The tumor extended further into the S1 sacral anterior foramen, in the shape of a dumbbell. The tumor was resected in several blocks posteriorly, and the dumbbell-shaped tumor in the S1 foramen was resected by widening the S1 foramen from behind. The posterior extension of the iliac tumor seemed prevented by the posterior sacroiliac ligament, and the tumor extended into the canal. Here, we report that the iliac chondrosarcoma extending into the spinal canal is rare for this tumor type. An understating of the tumor extension is important for planning the surgical strategy.
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http://dx.doi.org/10.1155/2021/5510075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313319PMC
July 2021

Neutrophil count reduction 1 month after initiating tocilizumab can predict clinical remission within 1 year in rheumatoid arthritis patients.

Rheumatol Int 2021 Jul 9. Epub 2021 Jul 9.

Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Neutropenia is a common adverse event of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients; however, the association between the decrease in neutrophil counts and the TCZ clinical efficacy remains inconclusive. This study aimed to examine whether TCZ-induced neutrophil decrease at 1 month predicts clinical remission within 1 year. We reviewed medical records of RA patients initiating TCZ between May 2011 and September 2019 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating TCZ) and 1, 3, 6, and 12 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. The ratio of neutrophil counts 1 month after initiating TCZ to those at baseline (neutrophil ratio) was also calculated. Among 255 TCZ-treated patients, 169 with valid CDAI and neutrophil counts were enrolled (with median age of 60 years and 79% females). Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in 75% and 83%, respectively, and 56% of the patients had concomitant methotrexate (median dose: 8 mg/week). Multivariate logistic regression analysis suggested baseline CDAI (odds ratio (OR) 0.96, p = 0.045), concomitant PSL (OR 0.42, p = 0.030), and the neutrophil ratio (OR 0.19, p = 0.011) as predictors of CDAI remission. Neutrophil ratio ≤ 0.8 was associated with achieving remission (Fisher's exact test, p = 0.02) with no apparent increase of severe infection. More than 20% reduction of neutrophil count 1 month after initiating TCZ predicts clinical remission within 1 year at an early treatment phase.
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http://dx.doi.org/10.1007/s00296-021-04944-xDOI Listing
July 2021

Salvage Oblique Lateral Interbody Fusion for Pseudarthrosis after Posterior/Transforaminal Lumbar Interbody Fusion: A Technical Note.

World Neurosurg 2021 Aug 12;152:107-112. Epub 2021 Jun 12.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objective: This study aims to demonstrate the efficacy of salvage oblique lumbar interbody fusion (OLIF) surgery for pseudarthrosis after posterior/transforaminal lumbar interbody fusion (PLIF/TLIF).

Methods: The study group were patients with leg or back pain induced by pseudarthrosis after PLIF/TLIF. These patients underwent salvage OLIF surgeries in our institutions between July 2015 and Oct 2019. We retrospectively evaluated their clinical and radiographic outcomes.

Results: Seven consecutive patients (all male; mean age 68.4 ± 9.3 years, range 53-81 years) were included in this study. There was no intraoperative complications in all cases. Six of 7 patients achieved bone union (at average 33.4 months follow-up) and had a successful postoperative course. Only 1 patient failed to gain bony fusion and required additional revision surgery due to progression of sagittal and coronal malalignment at 18 months after salvage OLIF surgery.

Conclusions: The salvage OLIF approach was useful option for pseudarthrosis after PLIF/TLIF. It enabled us to build a rigid anterior support, allowed for extensive curettage of intervertebral scar tissue, and reduced the rate of the complications associated with dealing with posterior scar tissue.
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http://dx.doi.org/10.1016/j.wneu.2021.06.020DOI Listing
August 2021

Rigid reconstruction with periacetabular multiple screws after the resection of malignant pelvic tumours involving the sacroiliac joint.

Int Orthop 2021 07 4;45(7):1793-1802. Epub 2021 Jun 4.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.

Background: Reconstruction of the pelvic ring after the resection of pelvic tumours involving the sacroiliac joint is challenging. Although pedicle screw and rod system reconstructions are commonly performed, failure at the early stage has been reported. Surgical procedures Reconstruction involving two or more strong anchor screws (iliac, ischial, and pubis screws) into the residual pelvis, connecting with at least two rods with minimal bending to the residual lumbosacral vertebra and contralateral pelvis.

Methods: The above reconstruction was performed for six malignant bone and soft-tissue pelvic tumours requiring Enneking type I + IV resection. A double-barreled free non-vascularized fibular graft was used in all patients, except for one. Patients were followed up for a mean period of 51 months (range, 9 to 96 months), and peri-operative complications, implant failure within the follow-up period, and the clinical results of surgery were investigated.

Results: The mean age of four females and two males at the initial surgery was 37.2 years. One patient developed a deep wound infection. Two patients died due to metastasis of the tumor. All patients were able to walk on their own within 12 weeks of surgery. There was no implant failure, except in two patients with contralateral lumbosacral rod fracture three and four years after surgery, for which one patient required rod replacement.

Conclusions: The incidence of implant failure, particularly around the resection site, was low, which may be attributed to multiple periacetabular screws and rods with minimal bending. Our rigid reconstruction method enables the rapid resumption of walking.
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http://dx.doi.org/10.1007/s00264-021-05096-0DOI Listing
July 2021

Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort.

Immunol Med 2021 May 25:1-10. Epub 2021 May 25.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Difficult-to-treat rheumatoid arthritis (D2T RA) is a multifactorial condition in which disease activity of RA persists despite consecutive treatment with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). To evaluate the prevalence and predictive risk factors of D2T RA in our institution, a single-center, retrospective study was conducted. Medical records of RA patients, who visited our hospital from 2011 to 2020 and had a follow-up of more than 6 months, were retrospectively reviewed. D2T RA was defined as RA with a disease activity score of 28 - erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or higher at the last visit, despite the use of at least two b/tsDMARDs. A logistic regression model was used to identify risk factors. A total of 672 patients were enrolled. The mean age at disease onset was 52.1 years and females were dominant (76.3%). After a mean follow-up of 46.6 months, patients with D2T RA accounted for 7.9% of overall patients. Multivariate analysis identified high rheumatoid factor (RF) levels (≥156.4 IU/mL, odds ratio [OR]: 1.95), DAS28-ESR (OR: 1.24), and coexisting pulmonary disease (OR: 2.03) as predictive risk factors of D2T RA. In conclusion, high RF levels, high DAS28-ESR, and coexisting pulmonary disease at baseline can predict the development of D2T RA.
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http://dx.doi.org/10.1080/25785826.2021.1928383DOI Listing
May 2021

Purse-string suture after ligating by endoloop for closing of the appendiceal stump is an alternative for endostapler in selected cases: A propensity score-matched study.

Asian J Endosc Surg 2021 Apr 21. Epub 2021 Apr 21.

Department of Surgery, Kita-Harima Medical Center, Ono, Japan.

Introduction: The closure of the appendiceal stump is a crucial part of a laparoscopic appendectomy, and an endoloop or endostapler is generally used. The endoloop can be more cost effective than the endostapler. However, reports have shown that the endoloop has a higher postoperative abdominal abscess rate than the endostapler in complicated appendicitis. At our institution, we perform a purse-string suture after ligating by endoloop to reduce postoperative abdominal abscess risk. This study aimed to clarify whether this method could reduce the incidence of postoperative abdominal abscess compared with the endostapler.

Methods: Patients with acute appendicitis were classified into the purse-string suture group (n = 149) and the endostapler group (n = 82). Postoperative outcomes were compared after propensity score matching (n = 47).

Results: No significant difference was found between the two groups in terms of the patient characteristics and postoperative complications, including abdominal abscess. However, the purse-string suture group had more drain placement and a shorter hospital stay than the endostapler group (P = .04 and P = .02, respectively). In patients with complicated appendicitis, there was less drain placement and a shorter hospital stay in the purse-string suture group than in the endostapler group (P < .01 and P < .01, respectively). This might have reflected the difficulty of the operation. All postoperative abdominal abscesses occurred in complicated appendicitis cases.

Conclusions: Endoloop with additional purse-string suture had a lower incidence of abscess than previous reports of using endoloop alone. Moreover, the postoperative abdominal abscess rate is similar between the two closure methods.
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http://dx.doi.org/10.1111/ases.12942DOI Listing
April 2021

Comparison of the drug retention and reasons for discontinuation of tumor necrosis factor inhibitors and interleukin-6 inhibitors in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

Arthritis Res Ther 2021 04 15;23(1):116. Epub 2021 Apr 15.

Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-chou Kobe-shi, Hyogo, 650-0017, Japan.

Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA).

Methods: Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model.

Results: Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59-0.86, p < 0.001). The adjusted cumulative incidence of discontinuation due to lack of effectiveness was lower with the IL-6i (HR = 0.46, 95%CI = 0.33-0.63, p < 0.001) while those due to adverse events (HR = 0.82, 95%CI = 0.56-1.18, p = 0.28) or achievement of clinical remission (HR = 1.09, 95%CI = 0.62-1.91, p = 0.76) were similar between the two groups.

Conclusions: In EORA patients initiating a TNFi or IL-6i, significantly higher drug retention was observed with IL-6i. Discontinuation due to lack of effectiveness was significantly less frequent in IL-6i while discontinuations due to adverse event or achievement of clinical remission were similar between the two groups.
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http://dx.doi.org/10.1186/s13075-021-02496-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048332PMC
April 2021

Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan college of rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

Mod Rheumatol 2021 Apr 15:1-25. Epub 2021 Apr 15.

Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.

Objectives: To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA).

Methods: We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications.

Results: After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25 to 2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications.

Conclusion: Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries.
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http://dx.doi.org/10.1080/14397595.2021.1913824DOI Listing
April 2021

Region specificity of rheumatoid foot symptoms associated with ultrasound-detected synovitis and joint destruction.

Mod Rheumatol 2021 Apr 14:1-28. Epub 2021 Apr 14.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objectives: We aimed to clarify the clinical implication of ultrasound (US)-detected foot joint inflammation in tightly controlled patients with rheumatoid arthritis (RA).

Methods: We evaluated bilateral foot joints (second to fifth metatarsophalangeal joints of forefoot; tarsometatarsal, cuneonavicular and midtarsal joints of midfoot) of 430 RA patients for synovitis using Power Doppler (PD) imaging by US. We made a cross-sectional and a 3-year longitudinal analysis about the associations of US-detected synovitis with clinical, laboratory and radiographic data as well as foot-specific outcomes using a self-administered foot evaluation questionnaire (SAFE-Q).

Results: The US-detected foot synovitis was seen in 28% of patients. The US-detected synovitis was closely related to 28 joint-disease activity score (DAS28) more in the forefoot than in the midfoot, while related to joint destruction in both. Multiple regression analyses showed significant associations between midfoot PD positivity and SAFE-Q in the remission group. SAFE-Q was worsened after the 3-year interval, but PD positivity at baseline did not contribute to the changes. On the other hand, destruction of the joints with US-detected synovitis significantly progressed in 3 years than with not.

Conclusions: US-detected synovitis on foot joints were related to systemic inflammation, clinical symptoms, and future joint destruction with region specificity.
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http://dx.doi.org/10.1080/14397595.2021.1912905DOI Listing
April 2021

Urinary sodium-to-potassium ratio associates with hypertension and current disease activity in patients with rheumatoid arthritis: a cross-sectional study.

Arthritis Res Ther 2021 03 27;23(1):96. Epub 2021 Mar 27.

Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.

Background: Excessive salt intake is thought to exacerbate both development of hypertension and autoimmune diseases in animal models, but the clinical impact of excessive salt in rheumatoid arthritis (RA) patients is still unknown. We performed a cross-sectional study to clarify the associations between salt load index (urinary sodium-to-potassium ratio (Na/K ratio)), current disease activity, and hypertension in an RA population.

Methods: Three hundred thirty-six participants from our cohort database (KURAMA) were enrolled. We used the spot urine Na/K ratio as a simplified index of salt loading and used the 28-Joint RA Disease Activity Score (DAS28-ESR) as an indicator of current RA disease activity. Using these indicators, we evaluated statistical associations between urinary Na/K ratio, DAS28-ESR, and prevalence of hypertension.

Results: Urinary Na/K ratio was positively associated with measured systolic and diastolic blood pressure and also with prevalence of hypertension even after covariate adjustment (OR 1.34, p <  0.001). In addition, increased urinary Na/K ratio was significantly and positively correlated with DAS28-ESR in multiple regression analysis (estimate 0.12, p <  0.001), as was also the case in gender-separated and prednisolone-separated sub-analyses.

Conclusion: Urinary Na/K ratio was independently associated with current disease activity as well as with prevalence of hypertension in RA patients. Thus, dietary modifications such as salt restriction and potassium supplementation should be investigated as a potential candidate for attenuating both disease activity and hypertension in RA patients.
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http://dx.doi.org/10.1186/s13075-021-02479-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004419PMC
March 2021

Emotional valence sensing using a wearable facial EMG device.

Sci Rep 2021 Mar 11;11(1):5757. Epub 2021 Mar 11.

Shimadzu Corporation, 3-9-4 Hikaridai, Seika-cho, Soraku-gun, Kyoto, 619-0237, Japan.

Emotion sensing using physiological signals in real-life situations can be practically valuable. Previous studies have developed wearable devices that record autonomic nervous system activity, which reflects emotional arousal. However, no study determined whether emotional valence can be assessed using wearable devices. To this end, we developed a wearable device to record facial electromyography (EMG) from the corrugator supercilii (CS) and zygomatic major (ZM) muscles. To validate the device, in Experiment 1, we used a traditional wired device and our wearable device, to record participants' facial EMG while they were viewing emotional films. Participants viewed the films again and continuously rated their recalled subjective valence during the first viewing. The facial EMG signals recorded using both wired and wearable devices showed that CS and ZM activities were, respectively, negatively and positively correlated with continuous valence ratings. In Experiment 2, we used the wearable device to record participants' facial EMG while they were playing Wii Bowling games and assessed their cued-recall continuous valence ratings. CS and ZM activities were correlated negatively and positively, respectively, with continuous valence ratings. These data suggest the possibility that facial EMG signals recorded by a wearable device can be used to assess subjective emotional valence in future naturalistic studies.
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http://dx.doi.org/10.1038/s41598-021-85163-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952725PMC
March 2021

Possible Association of Pedicle Screw Diameter on Pseudoarthrosis Rate After Transforaminal Lumbar Interbody Fusion.

World Neurosurg 2021 Jun 5;150:e155-e161. Epub 2021 Mar 5.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: Although pedicle screw sizes may affect the rate of bone union after lumbar fusion surgery, there is currently no supportive clinical evidence.

Methods: Eighty-five patients older than 50 years who underwent single-level L4/5 transforaminal lumbar interbody fusion with posterior pedicle screw (PS) fixation were analyzed. Patients with factors that potentially inhibit bone fusion, such as Parkinson disease, were excluded. Bone union was assessed using computed tomography and dynamic radiographs 1 year after surgery. Explanatory factors considered included sex, age, smoking, bone density, material of the cage, PS diameter (PSD), relative PS length, theoretical maximum PSD (PSD), which was defined as the maximum diameter of the screw that may be inserted without breaking cortical bone around the pedicle, and the filling index, which was defined as the difference between the cross-sectional area of maximum PS and actual PS (PSD 2 - PSD 2). Japanese Orthopaedic Association scores before and 1 year after surgery were evaluated as a clinical outcome.

Results: Nineteen levels were diagnosed as pseudoarthrosis. A multivariate logistic regression analysis identified a larger filling index (P = 0.016) and older age (P = 0.047) as risk factors for pseudoarthrosis. The Japanese Orthopaedic Association score 1 year after surgery and its recovery rate were significantly worse in patients with pseudoarthrosis than in those with fusion.

Conclusions: The selection of an appropriately sized screw is important for achieving rigid fusion after transforaminal lumbar interbody fusion. Preoperative planning using multiplanar reconstruction computed tomography is an important approach for ensuring good clinical results.
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http://dx.doi.org/10.1016/j.wneu.2021.02.117DOI Listing
June 2021

Vector incrimination and transmission of avian malaria at an aquarium in Japan: mismatch in parasite composition between mosquitoes and penguins.

Malar J 2021 Mar 6;20(1):136. Epub 2021 Mar 6.

Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan.

Background: Captive populations of penguins outside of their natural distributions are often maintained in outdoor facilities, such as zoos and aquariums. Consequently, such penguins in captivity are constantly exposed to mosquito vectors and risk of avian malarial infection during their active period from spring to autumn, which can be lethal to these naïve birds. Previous studies have investigated parasite prevalence in mosquitoes or penguins, but simultaneous investigations, which would be crucial to monitor the transmission dynamics and cycle within a facility, have not been done. To identify dominant lineages and trends, multiple-year surveys are recommended.

Methods: Avian malaria parasites (Plasmodium spp.) and related haemosporidia were tested in penguins and mosquitoes at an aquarium in Japan through multiple years from 2011 to 2018. Prevalence and dynamics were confirmed, and molecular analyses targeting the protozoal cytb gene were used to reveal the transmission cycle. Blood meals of mosquitoes were also identified using molecular methods.

Results: Parasite detection in penguins tended to fluctuate within an individual. Two Plasmodium lineages were consistently detected in mosquitoes that had fed on penguins and wild birds observed around the aquarium. Plasmodium lineage CXPIP09 was detected from both mosquitoes and penguins, suggesting active transmission at this facility. However, Plasmodium cathemerium PADOM02 was only detected in mosquitoes, which may be due to host, vector or parasite-related factors, or detection methods and their limits. Additionally, Haemoproteus larae SPMAG12 was detected from penguins, suggesting active transmission via biting midges.

Conclusions: The mismatch in parasite composition between penguins and mosquitoes shows that multiple aspects such as captive birds, wild birds and vector insects should be monitored in order to better understand and control avian malarial infection within ex-situ conservation facilities. Furthermore, morphological analyses would be needed to confirm competency and infection dynamics of avian malaria parasites.
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http://dx.doi.org/10.1186/s12936-021-03669-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937252PMC
March 2021

Habitual fish intake negatively correlates with prevalence of frailty among patients with rheumatoid arthritis.

Sci Rep 2021 Mar 3;11(1):5104. Epub 2021 Mar 3.

Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Frailty is a geriatric syndrome characterized by anabolic-catabolic imbalance and multisystem dysregulation resulting in increased adverse health outcomes, and is closely related with dietary habits in the general population. Although chronic inflammatory diseases are thought to accelerate development of frailty, correlations between rheumatoid arthritis (RA), frailty and dietary habits have not been examined. We performed a cross-sectional study using our cohort database (KURAMA cohort), and classified 306 participants into three groups (robust, prefrail and frail) according to the Study of Osteoporotic Fracture (SOF) criteria. Multivariate logistic analysis revealed that the presence of frailty/prefrailty was significantly correlated with the disease activity score (DAS28-ESR) (OR 1.70 (1.30-2.22), p < 0.0001). Additional analyses of frailty and food intake showed that 5 foods (fish, meat, milk, vegetables and fruits) of 20 groups on the questionnaire were inversely associated with the prevalence of frail/prefrail categories. In multivariate analysis with the five nutrients, fish intake (> two times a week) was an independent covariate negatively correlated with frailty/prefrailty (OR 0.35 (0.19-0.63), p = 0.00060). In conclusion, habitual fish intake may play a key role in nutritional intervention to prevent progression of frailty and RA.
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http://dx.doi.org/10.1038/s41598-021-84479-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930016PMC
March 2021

A cluster epidemic of influenza A(H1N1)pdm09 virus infection in four captive cheetahs (Acinonyx jubatus).

Zoonoses Public Health 2021 May 11;68(3):239-246. Epub 2021 Feb 11.

Avian Zoonosis Research Center, Tottori University, Tottori, Japan.

In January 2019, four cheetahs (Acinonyx jubatus) kept at a Japanese zoo intermittently showed respiratory signs following the incidence of seasonal influenza in animal caregivers. Respiratory materials (saliva, sputum and food tray swabs) were non-invasively collected from the four cheetahs. Although we were unable to isolate the virus, the NP gene of influenza A virus was detected in three of the cheetahs but not in the fourth cheetah that had nearly recovered. From a food tray swab which tested weakly positive by a commercial influenza detection kit, we were able to obtain the whole-genome sequence of the influenza A virus. Analysis of the genome, A/cheetah/Kanagawa/2/2019(H1N1), revealed that the virus was closely related to influenza A(H1N1)pdm09 viruses isolated from humans in Japan in the 2018-2019 winter. Production of haemagglutinin inhibition (HI) antibodies (64-128 HI) against an A(H1N1)pdm09 virus in plasma samples confirmed infection of all four cheetahs. The animals continued to produce antibodies for at least 314 days after disease onset. These findings strongly suggest that reverse zoonotic transmission of A(H1N1)pdm09 virus occurred from human to cheetah and subsequently from cheetah to cheetah in the zoo. We also show that specimens can be safely and non-invasively collected from non-domesticated animals and used to investigate respiratory infectious diseases.
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http://dx.doi.org/10.1111/zph.12813DOI Listing
May 2021

Indirect decompression via oblique lateral interbody fusion for severe degenerative lumbar spinal stenosis: a comparative study with direct decompression transforaminal/posterior lumbar interbody fusion.

Spine J 2021 06 2;21(6):963-971. Epub 2021 Feb 2.

Department of Orthopaedic Surgery, Kyoto University, Graduate School of Medicine.

Background Context: Previous studies have shown that oblique lateral interbody fusion (OLIF) can improve neurological symptoms via "indirect decompression." However, data are lacking in terms of its benefits when compared with conventional transforaminal lumbar interbody fusion (TLIF) and/or posterior lumbar interbody fusion (PLIF) approach, especially in patients with severe central canal stenosis.

Purpose: To investigate the clinical outcome of OLIF without posterior decompression versus conventional TLIF and/or PLIF in severe lumbar stenosis diagnosed on preoperative magnetic resonance imaging.

Study Design: Retrospective comparative study.

Patient Sample: Fifty-one patients who underwent OLIF and 41 patients who underwent conventional TLIF and/or PLIF.

Outcome Measures: Clinical outcome score by Japanese Orthopedic Association (JOA) score and radiographic outcomes (disc height and fusion rate on computed tomography scan).

Materials/methods: We retrospectively reviewed 51 patients who underwent OLIF with supplemental percutaneous pedicle screws (55 levels; OLIF group) and 41 patients who underwent conventional TLIF and/or PLIF (47 levels; TPLIF group). The cross-sectional area of the thecal sac was measured preoperatively in OLIF and TPLIF groups, but postoperatively only in the OLIF group. All patients were diagnosed with severe stenosis based on Schizas classification (Grade C or D) on magnetic resonance imaging. We compared radiographic and clinical outcome scores (JOA score) between the 2 groups at 1 year of follow-up. The radiographic evaluation included the fusion status and disc height on computed tomography scan. Surgical data and perioperative complications were also investigated.

Results: The baseline demographic data of the 2 groups were equivalent in preoperative diagnosis, JOA score, and disc height and/or angle. The cross-sectional area significantly increased postoperatively, which confirmed indirect decompressive effect in the OLIF group. The JOA score improved in both groups at the 1-year follow up (76.6% vs. 73.5% improvement rate in the OLIF and TPLIF groups, respectively). The fusion rate at the 1-year follow-up was higher in the OLIF group than in the TPLIF group (87.2% vs. 57.4%). The disc height restoration was also better in the OLIF group. The operative data demonstrated less estimated blood loss and operative time in the OLIF group.

Conclusions: OLIF and conventional TLIF and/or PLIF demonstrated comparable short-term clinical outcomes in the treatment of severe degenerative lumbar stenosis. However, the surgical and radiographic outcomes were better in the OLIF group. Surgeons should choose an appropriate approach on a case by case basis, recognizing the perioperative complications specific to each fusion procedure.
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http://dx.doi.org/10.1016/j.spinee.2021.01.025DOI Listing
June 2021

Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study.

Clin Rheumatol 2021 Jul 29;40(7):2673-2680. Epub 2021 Jan 29.

Department of Health and Sport Sciences, Osaka University, Graduate School of Medicine, Osaka, Japan.

Objectives: The aim of this multicenter, retrospective study was to clarify the retention rates of sarilumab (SAR), baricitinib (BAR), and tofacitinib (TOF) in patients with rheumatoid arthritis (RA).

Methods: Patients treated with either SAR (n = 62), BAR (n = 166), or TOF (n = 185) (females, 80.9%; age, 61.0 years; disease duration, 11.1 years; rheumatoid factor positivity, 84.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone dose, 5.3 mg/day [47.0%] and methotrexate dose, 8.8 mg/week [58.4%]; biologics- or Janus kinase inhibitors-switched cases 78.4%) were included. The reasons for drug discontinuation were classified into 4 major categories (lack of effectiveness, toxic adverse events, non-toxic reasons, and remission) by each attending physician. The drug retention rate was estimated at 18 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling.

Results: The discontinuation rates of SAR, BAR, and TOF for the corresponding reasons were as follows, respectively: lack of effectiveness (15.7%, 15.6%, and 21.5%; P = 0.84), toxic adverse events (15.8%, 12.1%, and 12.3%; P = 0.35), non-toxic reasons (10.9%, 7.7%, and 6.8%; P = 0.35), and remission (0.0%, 2.8%, and 0.0%; P = 1.0). The overall retention rates excluding non-toxic reasons and remission were as follows: 68.8% for SAR, 72.5% for BAR, and 66.7% for TOF (P = 0.54).

Conclusions: After adjustment by potent confounders, SAR, BAR, and TOF showed similar discontinuation rates due to lack of effectiveness and toxic adverse events. Key Points • This is the first retrospective multicenter study that aimed to clarify the retention rates and reasons for discontinuation of SAR, BAR, and TOF in patients with RA.
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http://dx.doi.org/10.1007/s10067-021-05609-7DOI Listing
July 2021

MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS.

Bone Res 2021 Jan 11;9(1). Epub 2021 Jan 11.

Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.

Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation, which results in decreased bone mineral density. The MEF2C locus, which encodes the transcription factor MADS box transcription enhancer factor 2, polypeptide C (MEF2C), is strongly associated with adult osteoporosis and osteoporotic fractures. Although the role of MEF2C in bone and cartilage formation by osteoblasts, osteocytes, and chondrocytes has been studied, the role of MEF2C in osteoclasts, which mediate bone resorption, remains unclear. In this study, we identified MEF2C as a positive regulator of human and mouse osteoclast differentiation. While decreased MEF2C expression resulted in diminished osteoclastogenesis, ectopic expression of MEF2C enhanced osteoclast generation. Using transcriptomic and bioinformatic approaches, we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1, which play a key role in osteoclastogenesis. Mechanistically, MEF2C binds to FOS regulatory regions to induce c-FOS expression, leading to the activation of NFATC1 and downstream osteoclastogenesis. Inducible deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis, a murine model of inflammatory arthritis. Our findings reveal direct regulation of osteoclasts by MEF2C, thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.
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http://dx.doi.org/10.1038/s41413-020-00120-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797478PMC
January 2021

The limitations of mono- and combination antibiotic therapies on immature biofilms in a murine model of implant-associated osteomyelitis.

J Orthop Res 2021 02 23;39(2):449-457. Epub 2020 Dec 23.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Treatment of implant-associated orthopedic infections remains challenging, partly because antimicrobial treatment is ineffective after a mature biofilm covers the implant surface. Currently, the relative efficacy of systemic mono- and combination standard-of-care (SOC) antibiotic therapies over the course of mature biofilm formation is unknown. Thus, we assessed the effects of cefazoline (CEZ), gentamicin (GM), and vancomycin, with or without rifampin (RFP), on Staphylococcus aureus biofilm formation during the establishment of implant-associated osteomyelitis in a murine tibia model. Quantitative scanning electron microscopy of the implants harvested on Days 0, 3, and 7 revealed that all treatments except CEZ monotherapy significantly reduced biofilm formation when antibiotics started at Day 0 (0.46- to 0.25-fold; p < 0.05). When antibiotics commenced 3 days after the infection, only GM monotherapy significantly inhibited biofilm growth (0.63-fold; p < 0.05), while all antibiotics inhibited biofilm formation in combination with RFP (0.56- to 0.44-fold; p < 0.05). However, no treatment was effective when antibiotics commenced on Day 7. To confirm these findings, we assessed bacterial load via colony-forming unit and histology. The results showed that GM monotherapy and all combination therapies reduced the colony-forming unit in the implant (0.41- to 0.23-fold; p < 0.05); all treatments except CEZ monotherapy reduced the colony-forming unit and staphylococcus abscess communities in the tibiae (0.40- to 0.10-fold; p < 0.05). Collectively, these findings demonstrate that systemic SOC antibiotics can inhibit biofilm formation within 3 days but not after 7 days of infection. The efficacy of SOC monotherapies, CEZ particularly, is very limited. Thus, combination treatment with RFP may be necessary to inhibit implant-associated osteomyelitis.
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http://dx.doi.org/10.1002/jor.24956DOI Listing
February 2021

Predictive Value of Heterogeneously Enhanced Magnetic Resonance Imaging Findings With Computed Tomography Evidence of Calcification for Severe Motor Deficits in Spinal Meningioma.

Neurospine 2021 Mar 4;18(1):163-169. Epub 2020 Dec 4.

Department of Orthopaedic Surgery, Kyoto University, Graduate School of Medicine, Kyoto, Japan.

Objective: Spinal meningioma is mostly benign, but they can exhibit neurological deficit. The relationship between neurological impairment and its radiographic findings, including intratumor magnetic resonance imaging (MRI) gadolinium enhancement and calcification in computed tomography (CT) scan, has not been studied. The purpose of this study was to investigate the association of preoperative image findings with neurological status in spinal meningioma.

Methods: Patients histologically diagnosed with spinal meningioma (n = 24), with an average age of 65.4 years, were included. The patients were classified into 2 groups, the homogeneous and heterogeneous groups, based on the contrast-enhanced T1-weighted MRI findings. Further, baseline demographics (age, sex, presence of preoperative paralysis [manual muscle testing 3 or worse neurological deficit in upper and/or lower limbs], tumor level, tumor length, and tumor occupation ratio), histological findings (Ki-67 index and histological subtypes), and CT findings (presence of intratumor calcification and Hounsfield unit [HU] value) were examined.

Results: Preoperative paralysis was observed in 33.3% (8 of 24) of the patients. These patients exhibited frequent heterogeneous contrast-enhanced MRI findings than those without preoperative paralysis (57.1% vs. 14.3%, p = 0.040). Further, preoperative paralysis did not associate with tumor level, tumor length, tumor-occupied ratio, Ki-67 index, and histological subtypes. The heterogeneous group showed 100% intratumor calcification and higher maximum HU than the homogeneous group (1,109.8 vs. 379.2, p = 0.001).

Conclusion: The heterogeneous contrast-induced MRI findings in the spinal meningioma were significantly associated with preoperative neurological impairment. Moreover, the intratumor contrast-deficient region in the heterogeneously enhanced tumors reflected marked calcification. The tumor hardness due to calcification may be related to preoperative neurological deficit.
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http://dx.doi.org/10.14245/ns.2040494.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021834PMC
March 2021

A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis.

Sci Rep 2020 11 27;10(1):20787. Epub 2020 Nov 27.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA.
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http://dx.doi.org/10.1038/s41598-020-77735-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695735PMC
November 2020

Fluctuation in anti-cyclic citrullinated protein antibody level predicts relapse from remission in rheumatoid arthritis: KURAMA cohort.

Arthritis Res Ther 2020 11 12;22(1):268. Epub 2020 Nov 12.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan.

Background: The positivity of anti-citrullinated protein/peptide antibodies (ACPAs) is a clinically useful diagnostic and prognostic marker in rheumatoid arthritis (RA). However, the significance of ACPA titer and its fluctuation remain unclear. This study aimed to assess the role of ACPA titer and its fluctuation on disease activity and the prognosis of RA.

Methods: Data obtained from the Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort was analyzed. Patients whose ACPA was measured at least twice between 2011 and 2019 and whose ACPA was positive at least once were included in this study. The association between the clinical variable and ACPA titer or its change was investigated.

Results: ACPA titer was measured in a total of 3286 patients, 1806 of whom were ACPA-positive at least once. Among them, the ACPA titer level was measured more than once in 1355 patients. Very weak correlation was observed between the ACPA titer level and disease activity. Additionally, there was no trend in the fluctuation of ACPA titer level in each patient; ACPA titer level fluctuated in some patients, but not in others. Patients with high variable levels of ACPA titer were more likely to relapse from remission. In the analysis of two consecutive ACPA measurements, the titer changes predicted the relapse from remission within a year of the second measurement.

Conclusions: The ACPA titer level fluctuated in some patients. Very weak correlation was observed between the ACPA titer level and disease activity. Fluctuation in ACPA titer level predicted relapse from remission in patients with RA.
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http://dx.doi.org/10.1186/s13075-020-02366-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664066PMC
November 2020

Long-term Radiographic Outcome of Occipitocervical Fixation: An Analysis of Fusion Rate and Spontaneous Subaxial Alignment Change at an Average 7-year Follow-up.

Spine (Phila Pa 1976) 2021 Feb;46(3):152-159

Department of Orthopaedic Surgery, Kyoto University, Graduate School of Medicine, Kyoto, Japan.

Study Design: Retrospective case series.

Objective: The aim of this study was to investigate the long-term radiographic outcome of patients who underwent occipitocervical fixation (OCF) using a modern screw/rod system.

Summary Of Background Data: Few studies have reported fusion rates and radiographic alignment changes in unfused subaxial segments after OCF at a long-term follow-up.

Methods: We retrospectively reviewed 22 patients who underwent OCF with a modern screw-based construct. The patients satisfied the minimum 2-year radiographic follow-up. Baseline demographics and the following pre- and postoperative sagittal alignment parameters were investigated. McGregor slope, O-C2 angle (OC2A), and C2-7 Cobb angle (CL). We grouped patients into those whose OC2A increased postoperatively (OC2A-increase group) and those whose OC2A decreased postoperatively (OC2A-decrease group). The postoperative sagittal alignment change was compared between the 2 groups at the final follow-up. The perioperative complications as well as fusion status based on computed tomography (CT) were investigated.

Results: The average follow-up period was 89.7 months. The lowest instrumented vertebra was at C2 (63.6%), C3 (18.1%), or C4 (18.1%). The fusion rate at the final follow-up was 77.2%. Postoperative dysphasia occurred in two patients (16.6%) in the OC2A-decrease group, whereas distal junctional kyphosis was observed in two patients (20.0%) in the OC2A-increase group. The OC2A-increase group demonstrated a mean 4.8° decrease in CL as a compensation for the 5.1° increase in OC2A. In contrast, the OC2A-decrease group showed a mean 9.2° increase in CL as a compensation for the 6.3° decrease in OC2A.

Conclusion: The CT-confirmed fusion rate of OCF was 77.2% over an average 89.7-month follow-up. Compensatory sagittal alignment change can occur in the unfused subaxial segments in conjunction with the alignment change in the instrumented OC segments, whereas the horizontal gaze was maintained. Strong consideration for the intraoperative measurement of the OC2A should be given during OCF to minimize both early and long-term complications.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003757DOI Listing
February 2021

Letter to the Editor concerning "Impact of spinal alignment and stiffness on impingement after total hip arthroplasty: a radiographic study of pre‑ and post‑operative spinopelvic alignment" by Hagiwara S, et al. (Eur Spine J. 2020; doi.org/10.1007/s00586-020-06589-z).

Eur Spine J 2020 12 14;29(12):3245-3246. Epub 2020 Oct 14.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.

Purpose: Dislocation is one of the remaining challenges after total hip arthroplasty. The spinopelvic mobility is considered to be the key to solve this problem and is of interest both to arthroplasty and spine surgeons. The purpose of this letter is to discuss the spinopelvic mobility and spinal stiffness described in the paper titled "Impact of spinal alignment and stiffness on impingement after total hip arthroplasty: a radiographic study of pre‑ and post‑operative spinopelvic alignment." by Hagiwara S, et al. METHODS: Examining the consistency between this paper and previously published papers on spinopelvic mobility.

Results: In this article, radiographic clearance of anterior impingement was defined as adding of femoral shaft angle and sacral slope (SS), and that of posterior impingement as adding SS and femoral shaft angle subtracting 90º in the sitting position. The impingement itself and other factors for dislocation including implant design, implant orientation, extra-prosthetic impingement and their mobilities are not considered in this parameter, and it is better if the validity of this parameter is shown. The term "rigid spine" and "spinal stiffness" are used in the manuscript. When THA candidates are evaluated, they are categorized according to the flexibility and/or sagittal balance. It would be better if the definition was described in the text and the clearance for impingement was shown to be affected by spinal stiffness.

Conclusion: The conclusions and titles are overstated from the results, but this paper is highly valuable in reminding spinal surgeons of the importance of spinopelvic alignment and mobility in THA.
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http://dx.doi.org/10.1007/s00586-020-06633-yDOI Listing
December 2020

Prevalence and antimicrobial-resistance profiles of Salmonella spp. isolated from green anoles (Anolis carolinensis) collected on the Haha-jima of the Ogasawara archipelago, Japan.

J Vet Med Sci 2020 Oct 16;82(10):1558-1561. Epub 2020 Sep 16.

College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan.

We investigated the prevalence of Salmonellaenterica and its antimicrobial resistance from 79 green anoles, the invasive alien species inhabits Haha-jima of the Ogasawara archipelago. Samples were collected during the period between 2009 and 2010. The resistance of S. enterica of these samples against 12 common antimicrobial agents was also determined. Salmonella strains, including serovar Oranienburg and Aberdeen, were detected from the large intestines of 30.4% of 79 green anole samples. And 37.5% of which were resistant to Oxytetracycline. This study suggests that green anoles may play an important role of the infection of S. enterica on this island. Attention is needed from the aspect of public and ecological health.
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http://dx.doi.org/10.1292/jvms.19-0632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653306PMC
October 2020

Cervical Myelopathy Caused by Invagination of Floating Anomalous C2 and C3 Laminae in the Spinal Canal.

Spine Surg Relat Res 2020 20;4(3):274-276. Epub 2019 Sep 20.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

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http://dx.doi.org/10.22603/ssrr.2019-0073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447344PMC
September 2019

Accuracy of fluoroscopic guidance with the coaxial view of the pedicle for percutaneous insertion of lumbar pedicle screws and risk factors for pedicle breach.

J Neurosurg Spine 2020 Aug 28:1-8. Epub 2020 Aug 28.

Objective: In this study the authors aimed to evaluate the rate of malposition, including pedicle breach and superior facet violation, after percutaneous insertion of pedicle screws using the coaxial fluoroscopic view of the pedicle, and to assess the risk factors for pedicle breach.

Methods: In total, 394 percutaneous screws placed in 85 patients using the coaxial fluoroscopic view of the pedicle between January 2014 and September 2017 were assessed, and 445 pedicle screws inserted in 116 patients using conventional open procedures were used for reference. Pedicle breach and superior facet violation were evaluated by postoperative 0.4-mm slice CT.

Results: Superior facet violation was observed in 0.5% of the percutaneous screws and 1.8% of the conventionally inserted screws. Pedicle breach occurred more frequently with percutaneous screws (28.9%) than with conventionally inserted screws (11.9%). The breaches in percutaneous screws were minor and did not reduce the interbody fusion rate. The angle difference between the percutaneous and conventionally inserted screws was comparable. Insertion at the L3 or L4 level, right-sided insertion, placement around a trefoil canal, smaller pedicle angle, and a small difference between the screw and pedicle diameters were found to be risk factors for pedicle breach by percutaneous pedicle screws.

Conclusions: Percutaneous pedicle screw placement using the coaxial fluoroscopic view of the pedicle carries a low risk of superior facet violation. The screws should be placed carefully considering the level and side of insertion, canal shape, and pedicle angle.
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http://dx.doi.org/10.3171/2020.5.SPINE20291DOI Listing
August 2020
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