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Objectives: Coronary flow reserve (CFR) is a strong predictor of cardiovascular events and prognosis in patients with coronary artery disease. This study aimed to evaluate preoperative factors associated with the unsuccessful restoration of CFR after coronary artery bypass grafting (CABG)., Methods: Included in this study were the 65 patients who presented with functionally significant left anterior descending artery (LAD) lesions confirmed by both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), and who underwent successful CABG at our hospital within the study period. After CABG, graft patency was confirmed by coronary computed tomography angiography, and CFR in the LAD artery was measured by echocardiography. We defined postoperative CFR <2.5 as impaired CFR, and CFR ≥2.5 as preserved CFR., Results: Of the 65 patients, 14 patients (22%) showed impaired CFR, while 51 patients had preserved CFR. Patients with impaired CFR had significantly higher HbA1c (6.7% vs. 6.0%, P < 0.01), greater use of insulin (43% vs. 4%, P < 0.01), longer lesion length (33 mm vs. 25 mm, P = 0.044), and lower iFR (0.69 vs 0.81, P = 0.01) than those with preserved CFR, although both groups had comparable FFR (0.65 vs 0.64, P = 0.46). In receiver operating characteristic curve analysis, iFR had a significantly larger area under the curve than FFR in terms of the prediction of impaired CFR (0.74 vs 0.42, P = 0.01)., Conclusions: Poorly-controlled preoperative diabetes, greater reliance on insulin, longer lesion length and lower iFR were associated with postoperative impaired CFR, suggesting the involvement of microvascular dysfunction., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization., Objectives: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA)., Methods: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort., Results: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA., Conclusions: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow Inc. The company performed the computational fluid dynamics, and artificial intelligence quantitative coronary plaque analysis but was not involved in the study design, collection, analysis, and interpretation of data; the writing of this paper; or the decision to submit it for publication. Dr Koo has received institutional research grants from Abbott, Philips, and HeartFlow Inc. Dr Nam has received institutional research grants from Abbott and Genoss. Dr Merkely has received direct personal payments for speaker fees or studies from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Medtronic, and Novartis and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr de Bruyne has received institutional unrestricted research grants from Abbott, Boston Scientific, and Biotronik; has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE, Bayer, Philips, HeartFlow Inc, Edwards Life Sciences, Sanofi, and Omega Pharma. Dr Ko has equity in Artrya and has received honoraria from Medtronic, Abbott Vascular, and Canon Medical. Dr Leipsic is a consultant for and holds stock options in HeartFlow Inc and modest personal core lab fees from Arineta. Dr Shah has received honoraria as a speaker for HeartFlow Inc. Dr Bax has received unrestricted research grants from Abbott and Edwards Lifesciences to the Department of Cardiology, Leiden University Medical Center, the Netherlands. Dr Shaw has received honoraria from HeartFlow Inc and Elucid Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) structural and functional changes have been reported in patients with aortic stenosis (AS) who have undergone transcatheter aortic valve implantation (TAVI); however, the relationship between change in LV structure and systolic function and tissue characteristics assessed via cardiovascular magnetic resonance imaging (CMRI) post-TAVI has been not fully elucidated. This study aimed to investigate this relationship in patients with severe AS who underwent TAVI and CMRI., Methods: In this retrospective study, 65 patients who underwent TAVI and CMRI at the 6-month follow-up were analyzed. The relationship between percent changes in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass (LVM) (⊿LVEDV, ⊿LVESV, ⊿LVEF, and ⊿LVM) and those in the native T1 value (⊿native T1) was analyzed using a correlation analysis. Moreover, extracellular volume fraction (ECV) value changes were analyzed., Results: The ⊿native T1 significantly decreased from 1292.8 (1269.9-1318.4) ms at pre-TAVI to 1282.3 (1262.6-1310.2) ms at the 6-month follow-up (P = 0.022). A significant positive correlation between ⊿LVEDV, ⊿LVESV, and ⊿LVM and ⊿native T1 (r = 0.351, P = 0.004; r = 0.339, P = 0.006; r = 0.261, P = 0.035, respectively) and a tendency toward a negative correlation between ⊿LVEF and ⊿native T1 (r = -0.237, P = 0.058) were observed. The ECV value increased significantly from 26.7 % (25.3-28.3) to 28.2 % (25.7-30.5) (P = 0.002)., Conclusions: The decrease in native T1 might be associated with LV reverse remodeling. Evaluating structural and functional changes using CMRI may be useful for patient management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chronic pain and numbness are common complaints in patients with ossification of the posterior longitudinal ligament of the spine (OPLL). However, it is unclear whether the current treatments are effective in patients with OPLL in terms of improving pain and numbness., Methods: A cross-sectional survey of patients with OPLL was conducted to determine patient satisfaction with surgery and drug therapy for pain and numbness, and its association with health-related quality of life. The survey was conducted by a patient association and its members, and anonymized data were analyzed by physicians. Comparisons between groups were made using T-tests or Kruskal-Wallis and Steel-Dwass tests, chi-square tests, and Fisher's exact tests., Results: Data from 121 patients with OPLL (age 69 ± 11 years, 69 males; 43 females; and 7 unknown) who completed a mailed questionnaire were analyzed. Of the 93 patients with a history of surgery for OPLL, 24% and 18% reported much improvement in pain and numbness, respectively. After surgery, 42% and 48% reported some improvement, and 34% and 34% reported no improvement, respectively. Patients whose numbness did not improve with surgery had a significantly poorer health-related quality of life than those who did. Of the 78 patients who received medication, only 2% reported "much improvement," 64% reported "some improvement," and 31% reported "no improvement at all." Compared to patients with OPLL only in the cervical spine, those with diffuse-type OPLL showed poorer improvement in numbness after surgery and poorer quality of life., Conclusions: The majority of patients with OPLL belonging to the association were unsatisfied with surgery and pharmacotherapy in terms of pain and numbness improvement, indicating that there is an unmet medical need for more effective treatment for chronic pain and numbness in patients with OPLL., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms., Methods: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness., Results: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL., Conclusions: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly., Level of Evidence: II, prospective cohort study., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients., Methods: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings., Results: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up., Conclusions: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Although severe cervical compressive-extension (CE) injuries are usually repaired using a combined anterior-posterior approach, the repair is possible using a posterior approach alone with reliable anchors. This study aimed to present the outcomes and imaging analysis results of posterior cervical decompression and fusion (PCDF) for severe CE injuries., Methods: We retrospectively reviewed 16 patients who underwent PCDF surgery for severe CE injuries (>50% subluxation) between January 2012 and December 2018. All patients completed 1-year follow-up, and their mean age at the time of surgery was 63.5 years. American Spinal Injury Association Impairment Scale (AIS) grade, kyphotic angle of lower vertebra (KALV), and anterior defect area of lower vertebra (ADLV) were assessed preoperatively., Results: Of 16 patients, nine patients improved at the final follow-up, and eight patients could walk with or without assistance. All patients achieved bone union postoperatively, but four patients showed progression of correction loss of ≥10°. Therefore, patients were divided into two groups: NL group with correction loss of <10°; L group with correction loss of ≥10°. All patients in L group showed KALV of ≥15°, while 10 of 12 patients in NL group showed KALV of <15°. Furthermore, all patients in L group showed ADLV of ≥50%, whereas all patients in NL group showed ADLV of <50%., Conclusions: PCDF is feasible and a favorable procedure for severe CE injuries that require early reduction and cervical spinal stabilization. However, in the cases of advanced destruction of the anterior vertebra, loss of correction after PCDF might occur postoperatively., Competing Interests: Declaration of competing interest We have no conflict of interest in this study., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: Symptomatic postoperative lumbar epidural hematoma (PLEH) may lead to poor outcomes even after evacuation. This study aimed to verify the short-term clinical outcomes after the evacuation of PLEH and to clarify the characteristics of the patients with poor postoperative outcomes., Methods: Twenty-five patients (average age; 70.4 years) underwent PLEH evacuation after lumbar spine surgery. The mean follow-up period was 12.0 (range 3-37) months. Pre and postoperative Japanese Orthopedic Association scores and visual analog scale (VAS) of low back pain (LBP), leg pain, and leg numbness were retrospectively collected. The dural sac cross-sectional area at the most compressed level was measured on magnetic resonance imaging. The patients were classified into 2 groups: poor outcome group (P group) had less than 50% of Japanese Orthopedic Associationrecovery rate and good group (G group) with 50% or more recovery rate., Results: The rate of delayed evacuation (over 24 hours of onset) was significantly higher in P group than in G group (P = 0.027). There was no significant difference in dural sac cross-sectional areabetween the 2 groups (P = 0.438). VAS of LBP, leg pain, and leg numbness in G group significantly improved postoperatively. Although VAS of LBP and leg pain in P group significantly improved postoperatively, there was no significant difference between the pre and postoperative VAS of leg numbness., Conclusions: Delayed evacuation of PLEH can lead to poor postoperative outcomes after lumbar spine surgery. Moreover, patients with poor outcomes remained with postoperative leg numbness. Early evacuation of symptomatic PLEH is key to avoid poor outcomes and persistent leg numbness., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The Japanese Orthopaedic Association (JOA) guideline for the management of lumbar spinal stenosis (LSS) was first published in 2011. Since then, the medical care system for LSS has changed and many new articles regarding the epidemiology and diagnostics of LSS, conservative treatments such as new pharmacotherapy and physical therapy, and surgical treatments including minimally invasive surgery have been published. In addition, various issues need to be examined, such as verification of patient-reported outcome measures, and the economic effect of revised medical management of patients with lumbar spinal disorders. Accordingly, in 2019 the JOA clinical guidelines committee decided to update the guideline and consequently established a formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline, incorporating the recent advances of evidence-based medicine., Methods: The JOA LSS guideline formulation committee revised the previous guideline based on the method for preparing clinical guidelines in Japan proposed by the Medical Information Network Distribution Service in 2017. Background and clinical questions were determined followed by a literature search related to each question. Appropriate articles based on keywords were selected from all the searched literature. Using prepared structured abstracts, systematic reviews and meta-analyses were performed. The strength of evidence and recommendations for each clinical question was decided by the committee members., Results: Eight background and 15 clinical questions were determined. Answers and explanations were described for the background questions. For each clinical question, the strength of evidence and the recommendation were both decided, and an explanation was provided., Conclusions: The 2021 clinical practice guideline for the management of LSS was completed according to the latest evidence-based medicine. We expect that this guideline will be useful for all medical providers as an index in daily medical care, as well as for patients with LSS., Competing Interests: Declaration of competing interest All guideline formulation committee members confirmed the COI through self-reporting at the time of preparation of this manuscript. Committee members with any COI declined to vote for applicable recommendation decisions. No companies or any other organizations were directly involved in any text pertaining to the guideline, including the recommendations for all CQs and BQs., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest.

Background: Whether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa., Methods: A total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR < 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups., Results: In total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P < 0.001). Similar proportions of MPS-derived ischemia were found when RFR. (70%, 34%, 24%, and 10%, P < 0.001), dPR (70%, 38%, 26%, and 10%, P < 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P < 0.001) were used in place of iFR., Conclusions: The prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The latest clinical guidelines are mandatory for physicians to follow when practicing evidence-based medicine in the treatment of low back pain. Those guidelines should target not only Japanese board-certified orthopaedic surgeons, but also primary physicians, and they should be prepared based entirely on evidence-based medicine. The Japanese Orthopaedic Association Low Back Pain guideline committee decided to update the guideline and launched the formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline with the latest data of evidence-based medicine., Methods: The Japanese Orthopaedic Association Low Back Pain guideline formulation committee revised the previous guideline based on a method for preparing clinical guidelines in Japan proposed by Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Two key phrases, "body of evidence" and "benefit and harm balance" were focused on in the revised version. Background and clinical questions were determined, followed by literature search related to each question. Appropriate articles were selected from all the searched literature. Structured abstracts were prepared, and then meta-analyses were performed. The strength of both the body of evidence and the recommendation was decided by the committee members., Results: Nine background and nine clinical qvuestions were determined. For each clinical question, outcomes from the literature were collected and meta-analysis was performed. Answers and explanations were described for each clinical question, and the strength of the recommendation was decided. For background questions, the recommendations were described based on previous literature., Conclusions: The 2019 clinical practice guideline for the management of low back pain was completed according to the latest evidence-based medicine. We strongly hope that this guideline serves as a benchmark for all physicians, as well as patients, in the management of low back pain., Competing Interests: Conflict of interest All guideline formulation committee members confirmed the COI through self-reporting. No companies or any other organizations were directly involved in any text pertaining to the guideline, including the recommendations for all CQs and BQs., (Copyright © 2021. Published by Elsevier B.V.)

Background: The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis., Methods: A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed., Results: Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P < 0.01, P < 0.01, respectively)., Conclusions: The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: To identify risk factors for significant blood loss (SBL) in cervical laminoplasty, especially regarding thrombocytopenia and coagulopathy resulting from non-alcoholic fatty liver disease (NAFLD)., Methods: We retrospectively investigated differences in patient background data, laboratory data at the time of admission, and surgery-related data of 317 patients who underwent cervical laminoplasty and were divided into SBL (estimated blood loss [EBL] + drainage [D] ≥500 g) and non-SBL (EBL + D < 500 g) groups. To evaluate liver status, we used the fibrous 4 index and considered fibrous 4 index ≥1.85 as a representative phenotype for NAFLD with liver fibrosis. In addition, the risk factor for perioperative SBL was investigated using multiple logistic regression analysis, and the cutoff value was calculated., Results: Incidence of perioperative SBL in cervical laminoplasty was 7.3% (23/317). Compared with the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower aspartate aminotransferase, longer operation time, and greater number of opened laminae. According to multivariate analysis, lower PLT and a greater number of opened laminae were identified as significant risk factors for perioperative SBL. The cutoff value of PLT for predicting SBL was determined to be 16.7 × 10 4 /μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and greater EBL + D than the non-liver fibrosis group., Conclusions: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) via the distal radial access (DRA), called as snuffbox approach, recently has been increased worldwide due to fewer complications. Generally, since the diameter of distal radial artery is smaller than the radial artery, it is expected that the hemostasis duration can be shortened; however, there are no prospective studies. Furthermore, there is a lack of data about the feasibility of DRA for PCI., Methods: We prospectively collected data from 250 patients who were performed PCI via the DRA by three multi-center operators between March 2019 and December 2019. The primary outcome was hemostasis duration. Secondary outcomes were success rate of PCI, cannulation time, and puncture site complications., Results: Mean age of study population was 65.1 ± 10.3 years, success rate of PCI via the DRA was 99.2% (250/252) and 91.2% (228/250) patients was performed PCI via 6-French sheath. The cannulation time was 131 ± 98 s and the average hemostasis duration was 199 ± 50 min, and the median time was 180 [180-200] min. There are few minor hematomas (8.0%) and puncture site numbness (1.6%) with no radial artery occlusion., Conclusions: HEMOBOX trial first reported hemostasis duration for PCI using the DRA, approximately 3 h, with 99.2% success rate and few minor complications., Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03863652., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study sought to investigate the ability of combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) to differentiate plaque rupture (PR), plaque erosion (PE), or calcified nodule (CN) in acute myocardial infarction (AMI)., Background: Most acute coronary syndromes occur from coronary thrombosis based on PR, PE, or CN. In vivo differentiation among PR, PE, and CN is a major challenge for intravascular imaging., Methods: The study enrolled 244 patients with AMI who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and optical coherence tomography (OCT). Maximum lipid core burden index in 4 mm (maxLCBI 4mm ) was measured by NIRS. Plaque cavity and convex calcium was detected by IVUS. The OCT diagnosis of PR (n = 175), PE (n = 44), and CN (n = 25) was used as a reference standard., Results: In the development cohort, IVUS-detected plaque cavity showed a high specificity (100%) and intermediate sensitivity (62%) for identifying OCT-PR. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) for identifying OCT-CN. NIRS-measured maxLCBI 4mm was largest in OCT-PR (705 [interquartile range (IQR): 545 to 854]), followed by OCT-CN (355 [IQR: 303 to 478]) and OCT-PE (300 [IQR: 126 to 357]) (p < 0.001). The optimal cutoff value of maxLCBI 4mm was 426 for differentiating between OCT-PR and -PE; 328 for differentiating between OCT-PE and -CN; and 579 for differentiating between OCT-PR and -CN. In the validation cohort, the NIRS-IVUS classification algorithm using plaque cavity, convex calcium, and maxLCBI 4mm showed a sensitivity and specificity of 97% and 96% for identifying OCT-PR, 93% and 99% for OCT-PE, and 100% and 99% for OCT-CN, respectively., Conclusions: By evaluating plaque cavity, convex calcium, and maxLCBI 4mm , NIRS-IVUS can accurately differentiate PR, PE, and CN., Competing Interests: Funding Support And Author Disclosures Dr. Madder has received speaker honoraria and research support from Infraredx; and has served on the advisory board of SpectraWave. Dr. Akasaka has received lecture fees from Abbott Vascular, Terumo, and Nipro; and has received research grants from Abbott Vascular, Terumo, and Nipro. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion., Methods: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated., Results: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence., Conclusions: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Studies on the clinical and radiographic risk factors for the residual low back pain beyond 6 months after osteoporotic vertebral fractures (OVFs) are lacking. Hence, this study aimed to characterize a patient population with residual low back pain 48 weeks after acute OVFs and to identify the risk factors associated with residual low back pain., Methods: This prospective multicenter study included 166 female patients aged 65-85 years with acute one-level OVFs. We defined the residual low back pain as visual analog scale (VAS) for low back pain ≥3.5 at 48 weeks in this study, as VAS score ≥3.5 is used to describe moderate or severe pain. Thus, outcome and risk factor analyses were performed by comparing patients with VAS scores <3.5 and ≥ 3.5. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and 48 weeks., Results: Of the 166 patients analyzed, 58 complained of residual low back pain at 48 weeks after OVFs. At 0 weeks, the VAS score was significantly higher, and the JOABPEQ mental health score and anterior vertebral body compression percentage were significantly lower in patients with persistent pain 48 weeks after OVFs. The independent risk factors in the acute phase for persistent pain 48 weeks after OVFs were a high VAS score, MRI T2 fluid-intensity image pattern, and a lower anterior vertebral body compression percentage., Conclusions: Severe low back pain, MRI T2 fluid-intensity image pattern, and severe vertebral body collapse in the acute phase were significant risk factors for residual low back pain 48 weeks after OVFs. Patients with acute OVFs who have these risk factors should be carefully monitored for the possible development of residual chronic low back pain., Competing Interests: Declaration of Competing Interest Hiroaki Nakamura is an associate editor of Journal of Orthopaedic Science. There are no other conflicts of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG)., Methods and Results: A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR <0.80. The rate of graft failure was significantly higher in vessels with negative iFR (>0.89) than in those with positive iFR (<0.89) (25.7% vs. 7.3%, p = 0.012). The graft failure rates increased as the preoperative iFR values rose (iFR <0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.002). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively., Conclusions: The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR., Competing Interests: Declaration of Competing Interest Dr. Shiono has received honoraria for publications and lectures from Phillips Volcano. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Coregistration system of instantaneous wave-free ratio (iFR) pullback and angiography has been developed to enhance benefits of physiology oriented percutaneous coronary intervention (PCI), but its reproducibility has not yet been fully assessed., Methods and Results: In 51 coronary arteries from 39 patients with stable coronary artery disease, iFR angio-coregistrations were repeated twice. The mean iFR values were comparable between the first and second studies (0.85 ± 0.12 vs. 0.84 ± 0.13, p = 0.97). In terms of a coronary segment with predominant iFR gradients defined by the largest segmental iFR gradients, the repeated iFR angio-coregistrations matched in 47 of 51 (92%) studies and showed good agreement (κ = 0.75) in overall vessels. When assessed only in vessels with positive iFR (≤0.89), iFR angio-coregistrations matched in 31 of 32 (97%) studies and showed an excellent agreement (κ = 0.91). The predominant iFR gradients in the repeated iFR angio-coregistrations demonstrated strong correlation (r = 0.96, p < 0.0001) and an excellent agreement: mean difference was 0.0006, and the lower and upper limits (mean difference ± 1.96 standard deviation) of agreement were -0.0312 and 0.0324., Conclusions: iFR angio-coregistration is highly reproducible and can precisely identify a suitable target for PCI., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Optical coherence tomography (OCT) requires intracoronary injection of contrast media to remove blood from the field of view during image acquisition. Contrast injection may cause a temporal increase in intracoronary pressure. The aim of this study was to compare the intracoronary pressure during contrast injection between OCT and coronary angiography., Methods: We measured intracoronary pressure by using a pressure guidewire during contrast injection for OCT and angiography in 30 coronary arteries (mean fractional flow reserve = 0.90 ± 0.03). Contrast media was injected into coronary artery through the guiding catheter by using a mechanical injector pump., Results: Intracoronary pressure before contrast injection was similar between OCT and angiography (systolic pressure: 123 ± 18 mmHg vs. 122 ± 19 mmHg, p = 0.863). Intracoronary pressure was increased due to contrast injection in both OCT (systolic pressure: 123 ± 18 mmHg to 132 ± 18 mmHg, p < 0.001) and angiography (systolic pressure: 122 ± 19 mmHg to 128 ± 19 mmHg, p < 0.001). The increase in intracoronary pressure was slightly greater in OCT compared with angiography (absolute increase of systolic pressure: 9 ± 2 mmHg vs. 6 ± 1 mmHg, p < 0.001; and relative increase of systolic pressure: 8 ± 2% vs. 5 ± 1%, p < 0.001). Intracoronary pressure during contrast injection was not significantly different between OCT and angiography (systolic pressure: 132 ± 18 mmHg vs. 128 ± 19 mmHg, p = 0.831)., Conclusions: Contrast injection for OCT induced significant but small increase in intracoronary pressure compared with that for angiography., (Copyright © 2019. Published by Elsevier Ltd.)

Background: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery., Methods: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses., Results: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95% CI 1.378-9.599)., Conclusions: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to identify the incidence and causes of a second rise in C-reactive protein (CRP) levels following spinal instrumentation surgery and to help determine how an abnormal CRP response should be interpreted and managed during postoperative care., Methods: The medical records of 948 patients who underwent instrumented spine fusion surgery and met the inclusion criteria were retrospectively reviewed to assess the frequency and causes of a second rise (SR) of CRP. A SR of CRP was defined when the CRP level after postoperative day 7 increased by more than 0.5 mg/dl from that at the previous time-point. The diagnostic cut-off value of CRP elevation for detection of surgical site infection (SSI) was determined. Cut-off values were analyzed using receiver operating characteristic (ROC) curves. Bayes' theorem was used to determine blood test posterior probabilities for SSI-positive cases using cutoff values of re-evaluated CRP levels., Results: SR of CRP occurred in 107 of the 948 patients. Of the patients with SR of CRP, 38 (35%) patients had developed SSI, 33 (31%) patients had causes other than SSI, and the remaining 36 patients had unidentified causes. Among the patients with SR, excluding those with causes other than SSI, the best diagnostic cut-off value of SR for detection of SSI was 3.04 mg/dl (area under the curve was 0.74). The posterior test probability was 84.4%., Conclusions: For patients with SR of CRP, who had no causes other than SSI, an SR value of 3.04 mg/dl correlated with a high probability of developing SSI., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: A consensus on the optimal surgical procedure for thoracolumbar OVF has yet to be reached due to the previous relatively small number of case series. The study was conducted to investigate surgical outcomes for osteoporotic vertebral fracture (OVF) in the thoracolumbar spine., Methods: In total, 315 OVF patients (mean age, 74 years; 68 men and 247 women) with neurological symptoms who underwent spinal fusion with a minimum 2-year follow-up were included. The patients were divided into 5 groups by procedure: anterior spinal fusion alone (ASF group, n = 19), anterior/posterior combined fusion (APSF group, n = 27), posterior spinal fusion alone (PSF group, n = 40), PSF with 3-column osteotomy (3CO group, n = 92), and PSF with vertebroplasty (VP + PSF group, n = 137)., Results: Mean operation time was longer in the APSF group (p < 0.05), and intraoperative blood loss was lower in the VP + PSF group (p < 0.05). The amount of local kyphosis correction was greater in the APSF and 3CO groups (p < 0.05). Clinical outcomes were approximately equivalent among all groups., Conclusion: All 5 procedures resulted in acceptable neurological outcomes and functional improvement in walking ability. Moreover, they were similar with regard to complication rates, prevalence of mechanical failure related to the instrumentation, and subsequent vertebral fracture. Individual surgical techniques can be adapted to suit patient condition or severity of OVF., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis., Methods: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test., Results: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups., Conclusions: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Disseminated fusariosis (DF) is a rare life threatening fungal infection in immunocompromised hosts. We herein report a case of a fatal DF mimicking varicella zoster virus (VZV) infection that was emerged from a localized genital infection during cord blood transplantation (CBT) in a patient with severe aplastic anemia (SAA). The patient developed an ulcer following small painful vesicles mimics herpes simplex virus infection (HSV) on the glans penis before CBT, but a Fusarium species was identified. Despite administration of voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion was extended to extensive skin looked like VZV infection and the patients died after CBT. Massive fusarium infiltration was detected in multiple organs at autopsy. A genetic analysis of the mold identified Fusarium solani after his death. It should be noted that in patients with fusarium infection, localized and disseminated lesions of fusarium infection sometimes mimic HSV and VZV infections, which hampers an early diagnosis., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues., Statement of Significance: Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO., Methods: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan-Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS)., Results: HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health)., Conclusions: Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Intervertebral disk (IVD) degeneration causes debilitating low back pain in much of the worldwide population. No efficient treatment exists because of an unclear pathogenesis. One characteristic event early in such degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVDs. Excessive biomechanical loading may also be a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic strategy for the treatment of IVD degeneration induced by biomechanical stress. A TUNEL assay showed that NP cell-agarose three-dimensional composite cultures subjected to uniaxial, unconfined, static, compressive loading exhibited a time-dependent increase in apoptosis. Western blot analysis revealed the up-regulation of several extracellular matrix-degrading enzymes and down-regulation of tissue inhibitor of metalloproteinase 1. These responses to compressive loading were all significantly inhibited by caspase 3 siRNA. In the in vivo model of compressive loading-induced IVD degeneration, a single local injection of caspase 3 siRNA significantly inhibited IVD degeneration by magnetic resonance imaging, histological findings, IHC, and TUNEL assay. The present study suggests that caspase 3 siRNA attenuates overload-induced IVD degeneration by inhibiting NP cell apoptosis and the expression of matrix-degrading enzymes., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Surgical treatment for severe circumferentially fixed cervical kyphosis has been challenging. Both anterior and posterior releases are necessary to provide the cervical mobility necessary for fusion in a corrected position., Objective: In two case reports, we describe the circumferential osteotomy of anterior-posterior-anterior surgical sequence, and the efficacy of this technique when cervical pedicle screw fixation for severe fixed cervical kyphosis is used., Case Description: Etiology of fixed cervical kyphosis was unknown in one patient and neurofibromatosis in one patient. Both patients had severe fixed cervical kyphosis as determined by cervical radiographs and underwent circumferential osteotomy and fixation via an anterior-posterior-anterior surgical sequence and correction of kyphosis by pedicle screw fixation., Conclusion: Severe fixed cervical kyphosis was treated successfully by the use of circumferential osteotomy and pedicle screw fixation. The surgical sequence described in this report is a reasonable approach for severe circumferentially fixed cervical kyphosis and short segment fixation can be achieved using pedicle screws., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Using β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and β-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (∆log10 CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 μg h/ml, was 64-128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.

Garenoxacin showed the most potent chlamydial activity against Chlamydia trachomatis D/UW-3/Cx among three tested quinolones and azithromycin. The DNA gyrase genes, gyrA and gyrB, of C. trachomatis D/UW-3/Cx were cloned and the GyrA and GyrB subunits of DNA gyrase protein were separately expressed as histidine-tagged proteins in Escherichia coli. The mean 50% inhibitory concentration (IC(50)) of garenoxacin against the supercoiling activity of C. trachomatis D/UW-3/Cx gyrase was 2.9 ± 0.4 μg/ml, which was the most potent inhibitory activity against DNA gyrase among the quinolones tested in this study. At an extracellular concentration of 0.5 μg/ml, the cellular-to-extracellular concentration ratio of garenoxacin was 15.3 ± 1.3, equivalent to that of moxifloxacin and greater than that of levofloxacin. In a time-kill experiment, after exposure to garenoxacin at a concentration of 0.5 μg/ml at 0-6, 5-11, and 24-30 h after infection, the percentages of recoverable chlamydial inclusion-forming units were 11.1 ± 3.3, 0.6 ± 0.1, and 2.6 ± 0.5%, respectively. On transmission electron microscopy observation, after exposure to garenoxacin at 24-30 h after infection, some C. trachomatis elementary bodies remained in the inclusion body; however, the reticulate bodies were completely disrupted. In conclusion, garenoxacin is expected to be a useful quinolone in the treatment of infectious diseases caused by C. trachomatis.

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime and ceftriaxone, with minimum inhibitory concentrations (MICs) of cefixime of 0.125-0.25 microg/ml and ceftriaxone of 0.031-0.125 microg/ml, were isolated from male urethritis patients in Tokyo, Japan, in 2006. The amino acid sequences of PenA, penicillin-binding protein 2, in these strains were of two types: PenA mosaic and nonmosaic strains. In the PenA mosaic strain, some regions in the transpeptidase-encoding domain in PenA were similar to those of Neisseria perflava/sicca, Neisseria cinerea, Neisseria flavescens, Neisseria polysaccharea, and Neisseria meningitidis. In the PenA nonmosaic strain, there was a mutation of Ala-501 to Val in PenA. In addition, we performed homology modeling of PenA wild-type and mosaic strains and compared them. The results of the modeling studies suggested that reduced susceptibility to cephems such as cefixime and ceftriaxone is due to a conformational alteration of the beta-lactam-binding pocket. These results also indicated that the mosaic structures and the above point mutation in PenA make a major contribution to the reduced susceptibility to cephem antibiotics.

Altered N-glycosylation occurs in many diseases. In rheumatoid arthritis (RA), for example, reduction in galactose residues in IgG and an increase in fucose residues in alpha1-acid glycoprotein have been observed. To further analyse N-glycans in disease, we show N-glycan profiling from whole serum employing reversed phase high performance liquid chromatography/negative-ion mode by sonic spray ionization ion trap mass spectrometry with pyridylamination. Profiles from female 15 RA patients and 18 aged-matched healthy women were compared. The most significant change seen in RA was decreased levels of mono-galactosyl bi-antennary N-glycans, in agreement with the previous reports regarding IgG. We also show previously unreported differences between isomers and increased tri-antennary oligosaccharides. These results indicate that LC-MS analysis of whole serum N-glycans can identify N-glycan alterations in RA and that this is a promising method both for studies of RA mechanisms and diagnosis.

We compared the antibacterial effects and the emergence of resistance to tosufloxacin or levofloxacin for Streptococcus pneumoniae by simulating the serum concentration according to the Japanese clinical regimens using an in vitro pharmacokinetic-pharmacodynamic model. For quinolone-susceptible strain ATCC49619, tosufloxacin showed bactericidal activity, given that both the AUC(0-24h)/MIC ratios at the dosage of 150 mg t.i.d. and 300 mg b.i.d. of tosufloxacin tosilate were 138 and 193, and the C(max)/MIC ranges were 7.93-10.2 and 15.9-17.6, respectively, which were greater than those of levofloxacin (100 mg t.i.d. and 200 mg b.i.d.). The greater area above the killing curves (AAKCs) or shorter time to achieve 99.9% killing (99.9% KT) in both models of tosufloxacin than those of levofloxacin was related to their larger AUC(0-24h)/MIC and C(max)/MIC. Exposure of only 100 mg t.i.d. of levofloxacin led to outgrowth of the parC mutants, which were twofold less susceptible to levofloxacin than the parent strain. Neither of the tosufloxacin tosilate regimens resulted in isolation of resistant mutants of this strain. For the parC mutant strain D-3197, both the AUC(0-24h)/MIC and C(max)/MIC ratios of tosufloxacin were greater than those of levofloxacin, which resulted in comparable or better bactericidal activity as compared to those of levofloxacin. However, both fluoroquinolones and both regimens led to outgrowth of resistant mutants, which possessed a mutation in gyrA in addition to parC. In conclusion, tosufloxacin is superior to levofloxacin in bactericidal activity against S. pneumoniae in the Japanese clinical regimens, especially in the quinolone-susceptible strain, without emergence of resistant subpopulations.

Using an intestinal methicillin-resistant Staphylococcus aureus (MRSA)-carrying rat model, we compared the influence of piperacillin (PIPC) on the intestinal flora to those of cefazolin (CEZ), cefmetazole (CMZ), and flomoxef (FMOX). The number of MRSA did not increase after PIPC and CEZ administrations compared with the nontreated group. However, it significantly increased in the cases of FMOX and CMZ administration (P < 0.01). In the FMOX- and CMZ-treated groups, the intestinal flora was severely disrupted and the recovery of the number of Escherichia coli and Bacteroides spp. cells was delayed. On the other hand, in the PIPC- and CEZ-treated groups, the rapid recovery of bacteria that composed the intestinal flora was observed. The C(max)/MIC(50) and C(trough)/MIC(50) ratios in E. coli and Bacteroides spp. in the case of FMOX and CMZ were relatively higher than those in the case of the PIPC- and CEZ-treated groups.

A new catalytic method for the determination of silver(I) was developed based on a metal exchange reaction between ethylenediaminetetraacetatomercury(II) (Hg(II)-EDTA) in the aqueous phase and bis(diethyldithiocarbamato)copper(II) (Cu(II)-DDTC) in the organic phase. This exchange reaction (Cu(II)-DDTC(org)+Hg(II)-EDTA-->Hg(II)-DDTC(org)+Cu(II)-EDTA, where org denotes the organic phase) was observed to proceed slowly and the Cu(II)-DDTC complex transferred quantitatively to Hg(II)-complex in the organic phase in the equilibrium state. In this system, silver(I) acts as the catalyst and can be determined by measuring the decrease in the absorbance of the Cu(II)-DDTC complex (lambda(max)=435 nm). The reaction was applied to the extractive flow injection analysis of silver(I). The present method allows the determination of silver(I) at 10(-7) mol dm(-3) level with the sampling frequency of 30 h(-1). The relative standard deviation of 0.28% (n=10) was obtained at 4.0x10(-7) mol dm(-3) of silver(I).