Genomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors.

Our understanding of neoadjuvant treatment with microtubule inhibitors (MTIs) for triple negative breast cancer (TNBC) remains limited. To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Lower PIK3CA, PTEN, and HRAS mutations were found in homologous recombination deficiency (HRD)-high (HRD score ≥ 42) tumors with higher pCR rates. When HRD-high tumors were stratified by tumor BRCA mutation status, the pCR rates in BRCA2-mutated tumors were higher (83% vs. 36%). Transcriptomic profiling of TP53-positive tumors identified downregulation of FGFR2 (false discovery rate p value = 2.07e-7), which was also the only common gene between HRD-high and -low tumors with pCR/quasi-pCR treated with paclitaxel and eribulin combined with carboplatin, respectively. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.

Abdominal Arterial Translation in Lower Lumbar Spine Level Due to Positional Change: A Clinical Survey Using Intraoperative Computed Tomography.

Background: Abdominal vascular injury, a fatal complication of lumbar disc surgery, should concern spine surgeons. This study aimed to compare the position of the abdominal arteries in the supine and prone positions and the factors involved. Thirty patients who underwent lumbar surgery by posterior approach were included. Methods: All patients underwent computed tomography (CT) preoperatively in the supine position and intraoperatively in the prone position. In the CT axial image, at the L4, L4/5 disc, L5, and L5/S1 disc level, we measured the shortest distance between the abdominal arteries and the vertebral body (SDA: shortest distance to the aorta), and the amount of abdominal arterial translation, defined as "SDA on intraoperative CT" minus "SDA on preoperative CT". Additionally, the preoperative CT axial images were evaluated for the presence of aortic calcification. Results: No significant difference in SDA values based on patients' positions was observed at each level. In males, the supine position brought the abdominal artery significantly closer to the spine at the left side of the L5/S level (p = 0.037), and, in cases of calcification of the abdominal artery, the abdominal artery was found to be closer to the spine at the left side of the L4/5 level (p = 0.026). Conclusions: It is important to confirm preoperative images correctly to prevent great vessel injuries in lumbar spine surgery using a posterior approach.

Bladder cancer risk stratification with the Oncuria 10-plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms.

BACKGROUND: No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories. METHODS: We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow-based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. All three analyzers quantify fluorescence signals generated by the Oncuria assay. RESULTS: All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically < 5%. While the most contemporary instrument, the FlexMap 3D, output higher raw fluorescence values than the two comparator systems, standard curve slopes and analyte concentrations determined in urine samples were concordant across all three units. Forty-four percent of BC samples registered ≥ 1 analyte above the highest standard concentration, i.e., A1AT (n = 7/18), IL-8 (n = 5), and/or ANG (n = 2), while only one control sample registered an analyte (A1AT) above the highest standard concentration. CONCLUSION: Multiplex BC assays generate detailed molecular signatures useful for identifying BC, predicting treatment responsiveness, and tracking disease progression and recurrence. The similar performance of the Oncuria assay across three different analyzer systems supports test adaptation by clinical and research laboratories using existing xMAP platforms. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT04564781, NCT03193528, NCT03193541, and NCT03193515.

Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. METHODS: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. RESULTS: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. CONCLUSION: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Bladder cancer risk stratification with the Oncuria 10-plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms.

Background: No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories. Methods: We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. Results: All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically <5%. While the most contemporary instrument, the FlexMap 3D, output higher raw fluorescence values than the two comparator systems, standard curve slopes and analyte concentrations determined in urine samples were concordant across all three units. Forty-four percent of BC samples registered ≥1 analyte above the highest standard concentration, i.e., A1AT (n=7/18), IL-8 (n=5), and/or ANG (n=2). In Controls, A1AT was higher in one sample. Conclusion: Multiplex BC assays generate detailed molecular signatures useful for identifying BC, predicting treatment esponsiveness, and tracking disease progression and recurrence. The similar performance of the Oncuria assay across three different analyzer systems supports test adaptation by clinical and research laboratories using existing xMAP platforms. Trial Registration: This study was registered at ClinicalTrials.gov as NCT04564781, NCT03193528, NCT03193541, and NCT03193515.

Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells.

Several chemotherapeutic drugs induce senescence in cancer cells; however, the mechanisms underlying intracellular pH dysregulation in senescent cells remain unclear. Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2) plays a critical role in maintaining pH homeostasis in cellular compartments. Herein, we report the regulatory role of ATP6AP2 in senescent breast cancer cells treated with doxorubicin (Doxo) and abemaciclib (Abe). A decline in ATP6AP2 triggers aberrant pH levels that impair lysosomal function and cause immune profile changes in senescent breast cancer cells. Doxo and Abe elicited a stable senescent phenotype and altered the expression of senescence-related genes. Additionally, senescent cells show altered inflammatory and immune transcriptional profiles due to reprogramming of the senescence-associated secretory phenotype. These findings elucidate ATP6AP2-mediated cellular pH regulation and suggest a potential link in immune profile alteration during therapy-induced senescence in breast cancer cells, providing insights into the mechanisms involved in the senescence response to anticancer therapy.

Association between Preoperative Urine Culture and Urinary Tract Infection after Spinal Surgery.

STUDY DESIGN: This is a retrospective study. PURPOSE: This study assessed risk factors accounting for urinary tract infections (UTIs) to determine whether preoperative asymptomatic UTI (aUTI) could be used to predict UTIs in patients after spinal surgery. OVERVIEW OF LITERATURE: UTI is a spinal surgery complication that increases the incidence of surgical site infections. However, the risk factors for UTIs after spinal surgery remain unclear. METHODS: This study included 509 (mean age, 54.5 years; 239 males and 270 females) patients who underwent posterior spine surgery at the department of the current study. First, clean catch urine was collected, after which a urine culture was performed for all patients before surgery. Preoperative detection of the aUTI (>105 colony-forming units/mL) rate was then determined. Subsequently, risk factors for postoperative UTI were evaluated using logistic regression analysis with the following as independent variables: age, sex, obesity, diabetes, spinal cord tumor, the preoperative Japanese Orthopedic Association (JOA) score, JOA-bladder function, preoperative urine culture positivity, aUTI, preoperative Escherichia coli detection, the postoperative catheter placement period, instrumentation, number of surgical levels, surgery duration, and blood loss. RESULTS: The preoperative aUTI and postoperative UTI incidences were 8.1% and 4.1%, respectively. Furthermore, multivariate logistic analysis showed that the risk factor for postoperative UTI was preoperative aUTI (odds ratio, 4.234; 95% confidence interval, 1.532-11.702; p=0.005). CONCLUSIONS: Preoperative aUTI is a risk factor for UTI in patients after spinal surgery.

RUNX1-Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors.

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

Molecular vulnerabilities and therapeutic resistance in hormone receptor positive and HER2 dependent breast cancer tumours.

Over the past two decades, high sensitivity to HER2-amplified primary breast cancers has been achieved with HER2-targeted therapies. CDK4/6 inhibitors have long been identified as a potential treatment option for advanced breast cancer patients. However, acquired HER2 heterogeneity leading to resistance during the treatment has been identified as a bottleneck. This review focuses on the recent resistance mechanisms identified and potential therapeutic targets for conventional and combination endocrine therapies with CDK4/6 inhibitors by various breast cancer clinical trials and research groups in HER amplified and/or mutated breast cancer tumour. Activating HER2 alterations, JNK pathway, hyperactivated TORC1, co-mutations in HER2 and HER3, phenotypic changes of HER2, and few other advanced findings are identified as potential therapeutic targets in treating current HER2 endocrine therapy-resistant tumour. Along with the HER2-focused resistance mechanisms, we also describe how the microbiome may play a role in breast cancer therapy and its potential for new therapeutic strategies to overcome drug resistance in breast cancers.

Association between intraoperative computed tomography navigation system and incidence of surgical site infection in patients with spinal surgeries: a retrospective analysis.

PURPOSE: Although the use of intraoperative computed tomography (CT)-based navigation systems is unlikely to cause intraoperative contamination more than the use of intraoperative fluoroscopy, the association between intraoperative CT/navigation and surgical site infections (SSIs) remains unclear. We investigated the incidence of SSIs and the association between intraoperative CT/navigation and SSIs for spinal surgeries. METHODS: Of the 512 patients who underwent spinal surgery between April 2016 and December 2020, 304 underwent C-arm intraoperative fluoroscopy and/or Medtronic O-arm intraoperative CT/navigation system. We investigated the incidence of SSIs in patients with four techniques; no intraoperative imaging C-arm only, O-arm only, and both O- and C-arm used. Multivariate logistic analyses were conducted using the prevalence of SSIs as the dependent variable. The independent variables were age, sex, and potential confounders including preoperative Japanese Orthopaedic Association (JOA) score, use of instrumentation, C-arm, and/or O-arm. RESULTS: The incidence of the SSIs in patients with no imaging, C-arm only, O-arm only, and both modalities used was 1.9%, 7.3%, 4.7%, and 8.3%, respectively. There was no significant difference in the incidence of SSIs between the four techniques. Multivariate logistic analyses showed a significant correlation between the prevalence of SSI and JOA scores (odds ratio, 0.878; 95% CI 0.759-0.990) and use of instrumentation (odds ratio, 6.241; 95% CI 1.113-34.985), but not use of O-arm. CONCLUSIONS: The incidence of the SSIs in patients with only O-arm used was 4.7%. Preoperative clinical status and use of instrumentation, but not use of the O-arm, were associated with SSIs after spinal surgeries.

Occupational ionizing radiation-induced skin injury among orthopedic surgeons: A clinical survey.

BACKGROUND: This study aimed to assess orthopedic surgeons' attitudes and behaviors toward occupational radiation exposure and investigate the prevalence of occupational radiation-induced skin injury among orthopedic surgeons. Similarly, risk factors for the presence of radiation-induced skin injury were investigated. METHODS: Overall, 108 orthopedic surgeons were administered self-reported questionnaires about occupational radiation exposure, and their hands were then photographed. Their fields of expertise were classified into spine, arthroplasty, sports medicine, hand, oncology, rheumatoid arthritis, pediatric orthopedic, and resident. Dermatologists evaluated the surgeons' skin conditions and classified into 3 grades of injury: grade 0, no clinical symptoms; grade 1, careful observation required; and grade 2, detailed examination required. Logistic regression analysis was performed to investigate the factors related to the presence of radiation-induced skin injury. Crude and adjusted logistic regression analysis using the backward stepwise selection method was similarly conducted. Receiver operating characteristic curve (ROC) analysis was performed to estimate the predictive power of exposure time, occupational period, and accumulated annual exposure time for radiation-induced skin injury. RESULTS: In total, 93.5% of the surgeons were careful about occupational radiation exposure, of which 76.8% used a dosimeter. Skin changes in the hands were self-reported by 42.5% of the surgeons, and radiation-induced skin injury was diagnosed in 31.4%. The accuracy of the self-reported skin changes was 100% for grade 2 and 61.5% for grade 1. Adjusted regression analysis showed that dermatologists' diagnosis-related factors were self-reported skin changes (odds ratio [OR] 3.1) and spine surgeons (OR 3.2). ROC analysis demonstrated that an occupational period >21 years and an accumulated exposure time >6696 min were considered risk factors, with ORs of 4.07 and 5.99, respectively. CONCLUSIONS: Orthopedic surgeons, particularly spine surgeons, should be regularly examined by dermatologists early in their careers for early detection of radiation-induced skin injury on the hands.

Association between intra-operative hemodynamic changes and corrective procedures during posterior spinal fusion in adolescent patients with scoliosis: A case-control study.

ABSTRACT: Previous reports indicated that a decrease in intra-operative cardiac output and mean arterial pressure occurs due to thoracic cage deformities when patients with scoliosis are placed in the prone position. The aims of this study were to investigate the occurrence of hypotension during posterior spinal fusion in adolescent patients with scoliosis, and the association between hypotension, surgical procedures, changes of thoracic cage morphology.This retrospective, single-center, case-control study included 106 patients who underwent surgeries for spinal deformity at our institute between June 2014 and March 2020. The inclusion criteria were: age ≤19 years at the time of surgery, lowest instrumented vertebra over L5, posterior spinal fusion as the first surgery for scoliosis, and no severe cardiac or pulmonary disease pre-operatively. Finally, 49 patients met the criteria, and were divided to 3 groups as follows: thoracic constructive curve using a 6.0-mm cobalt-chromium alloy circular rod (T-C group; n = 28); thoracolumbar/lumbar constructive curve using a 6.0-mm cobalt-chromium alloy circular rod (L-C group; n = 8); and thoracic constructive curve using a 5.5-mm cobalt-chromium alloy beam-like rod (T-B group; n = 13). The beam-like rod is characteristic as the rod is mounted to screw heads without cantilever force. Intra-operative changes in circulation associated with corrective procedures, perioperative data, and sagittal depth and sternum deviation of thoracic cage were compared between the 3 groups.The T-C group had a higher rate of hypotension alarm than did the other groups (7 vs 0 vs 0; P = .047). Corrective procedures included rodding 4 times, rod rotation maneuver once, and direct vertebral rotation twice. Blood pressure was increased by pausing the correction procedures, increasing infusion, and administering vasopressors. The T-C and T-B groups had greater sternum deviation parameters than the L-C group, both before and after surgery. All parameters associated with sagittal depth and sternum deviation decreased significantly after surgery in the T-C and the T-B groups.In corrective surgery for constructive thoracic scoliosis, the corrective procedures requiring the application of compression force in the forward direction should be closely monitored in view of their possible influence on circulatory conditions.

Comparison of Short-Term Clinical Results and Radiologic Changes Between Two Different Minimally Invasive Decompressive Surgical Methods for Lumbar Canal Stenosis: Lumbar Spinous Process Splitting Laminectomy and Trans-Interspinous Lumbar Decompression.

STUDY DESIGN: A multicenter, retrospective study. OBJECTIVE: To clarify the clinical and radiological effects of removing interspinous contextures in lumbar decompression surgery for patients with lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: There have seldom been reports that have compared both clinical results and radiological changes among minimally invasive decompression methods. METHODS: Consecutive 52 patients underwent lumbar spinous process-splitting laminectomy (LSPSL), following which 50 patients underwent trans-interspinous lumbar decompression (TISLD). All patients presented with cauda equina type of lumbar spinal stenosis and underwent a minimum 1-year follow-up. The Japanese Orthopaedic Association (JOA) score and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score were evaluated to determine the extent of daily living activities. Propensity score (PS)-matched analysis was used to match patients' age and preoperative JOA scores between the two groups. Lumbar lordosis (LL), disc height (DH), segmental range of motion (ROM), and vertebral anterior translation were measured by functional lumbar lateral x-ray, and changes between preoperative and 1-year postoperative values were evaluated. RESULTS: Twenty-nine pairs of patients were selected by PS-matching. Mean JOA scores increased from 14.4 to 23.5 (mean recovery rate was 62.3%) in the LSPSL group and from 14.0 to 23.2 (61.3%) in the TISLD group at preoperative and 1-year follow-up, respectively. There were no significant differences in clinical results and changes in LL, ROM, and vertebral anterior translation in each group. The DH at L4/5 level at 1-year after surgery revealed significant decrease in the TISLD group compared with the LSPSL group. There was a correlation between preoperative DH and DH decrease in the LSPSL group, but not in TISLD group. CONCLUSION: Removal of interspinous contextures did not influence clinical outcomes at 1 year after surgery, but it may be likely to cause disc height loss when it applied at the L4/5 level.Level of Evidence: 3.

Modified K-Line in Neck Extension Is a Prognostic Indicator of the Surgical Outcome at 5 Years After Cervical Laminoplasty for Cervical Spondylotic Myelopathy.

STUDY DESIGN: A retrospective comparison of the surgical outcome after cervical laminoplasty for cervical spondylotic myelopathy (CSM) using a modified K-line based on lordosis in neck extension as a predictor: in K-line Back CSM (KB group), the K-line crosses the ventral edge of any of the spinous processes, whereas in K-line Front CSM (KF group), the K-line does not. OBJECTIVE: To investigate the neurological and radiological outcomes 5 years after surgery and the contact between the spinal cord and posterior elements after laminoplasty for CSM using the modified K-line. SUMMARY OF BACKGROUND DATA: No indicators on a lateral radiograph can predict the neurological outcome after laminoplasty for CSM. METHODS: Patients with CSM were divided into KB (n = 20) and KF groups (n = 13). We compared the postoperative Japanese Orthopedic Association (JOA) score, recovery rate, grip-and-release and foot-tapping test results, alignment, and contact between the spinal cord and posterior elements between the two groups. RESULTS: The postoperative JOA score and its recovery rate were significantly lower in the KB group (12.4 points and 34.1%, respectively) than in the KF group (14.1 points and 59.0%, respectively) at final follow-up (P = 0.0415 and 0.0458). The grip-and-release and foot-tapping test results improved significantly in the KF group but not in the KB group. In the KB group, a larger lordotic angle in extension at 1 year postoperatively continued until final follow-up. The rate of recovery of the JOA score in patients with contacts at both C4/5 and C5/6 and any contact in the KB group (-1.5% and 31.9%, respectively) were lower (P = 0.0013 and 0.0534, respectively) than those in the KF group (58.6% and 60.7%, respectively). CONCLUSION: The K-line Back predicts a poor neurological outcome after laminoplasty for CSM. Decompression with fusion may be recommended for these patients.Level of Evidence: 4.

Prevalence and associated factors of radiographic vertebral fractures in men: Rural population cross-sectional observation study in Japan.

BACKGROUND: Osteoporotic fractures constitute a major health concern in both women and men, particularly with the aging population. Many potential risk factors of vertebral fractures (VFx) have been identified in women, but not in men. Several reports have focused on the quality of life (QOL) of clinically diagnosed VFx, but not much has been reported on quantified QOL scores of incidental radiographic VFx in men. This cross-sectional study aimed to investigate the associated factors and the influence of incident radiographic VFx on QOL of men. METHODS: A total of 401 volunteer men aged 40 years or older (40-92 years) participated in this study. The mean age was 60.5 ± 11.8 years. Prevalent VFx were identified on the lateral lumbar spinal radiographs using the semiquantitative method. Bone mineral density, body composition, smoking, alcohol intake, past medical history, Mini-Mental State Examination, grip strength, gait speed, and biochemical markers were examined. QOL was evaluated using the 36-Item Short-Form Health Survey and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. RESULTS: Of the 401 subjects, 35 men (8.7%) had the prevalence of VFx. After adjustment for age, the presence of VFx was significantly associated with IGF-1 (odds ratio 0.985; p = 0.02). QOL scores were not significantly associated with VFx after adjustment for age. CONCLUSIONS: IGF-1 is the mediator of growth hormone, and IGF-1 stimulates the proliferation, differentiation, and mineralization of osteoblastic cells. The prevalence of VFx in men was 8.7%, and IGF-1 was significantly lower in the VFx group than in the non-VFx group.

Ten-Year Long-term Results of Modified Cervical Double-door Laminoplasty With C3 Laminectomy Preserving the Semispinalis Cervicis Inserted Into the Axis Compared With Those of Conventional Cervical Laminoplasty.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare long-term clinical and radiologic outcomes between conventional double-door laminoplasty (LP) (group A) and cervical LP with C3 laminectomy (group B). SUMMARY OF BACKGROUND DATA: Cervical LP with C3 laminectomy preserving the semispinalis cervicis inserted into the axis decreased the patients' postoperative axial pain and muscle atrophy, prevented interlaminar bony fusion, decreased limitations of daily living activity, including reduced postoperative neck mobility, and maintained the cervical range of motion (ROM) more effectively than conventional cervical LP reattaching the semispinalis cervicis in the short-term. MATERIALS AND METHODS: Group A included 14 patients with an average age of 56.6 years at the time of surgery (follow-up rate 58.1%), and group B included 21 patients with an average age of 56.3 years at the time of surgery (follow-up rate 29.1%). We evaluated the clinical results, which included the Japanese Orthopaedic Association (JOA) score, JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiologic results, including C2-C7 ROM, number of interlaminar bony fusions and presence of new spondylolisthesis at C3. RESULTS: There were no significant differences in preoperative and postoperative JOA scores, recovery rate of JOA score, and JOACMEQ. Significantly fewer patients in group B experienced interlaminar bony fusion at C2-C3 compared with those in group A. There was no significant difference in the presence of new spondylolisthesis at C3. In patients with cervical spondylotic myelopathy, the rate of decrease of C2-C7 ROM was significantly less in group B than in group A. In patients with ossification of the posterior longitudinal ligament, there was no significant difference in the rate of decrease of C2-C7 ROM between the groups. CONCLUSIONS: C3 laminectomy prevented interlaminar bony fusion at C2-C3. C3 laminectomy maintained cervical ROM in patients with cervical spondylotic myelopathy. There were no adverse events due to C3 laminectomy at 10 years postsurgery.

Accuracy of pedicle screw placement by fluoroscopy, a three-dimensional printed model, local electrical conductivity measurement device, and intraoperative computed tomography navigation in scoliosis patients.

INTRODUCTION: There are several assisted methods for the accurate placement of pedicle screw (PS), including fluoroscopy, a three-dimensional (3D) printed model, a local electrical conductivity measurement device (LECMD), and intraoperative computed tomography (CT) navigation. OBJECTIVES: This study aimed to investigate the accuracy of PS placement and clinical results using different assisted methods. METHODS: This study included 553 pedicle screws in 31 patients. We divided patients into the fluoroscopy (F) group (n = 79), 3D printed model and fluoroscopy (3D + F) group (n = 150), LECMD, 3D printed model, and fluoroscopy (LECMD + 3D + F) group (n = 171), and the intraoperative CT navigation (N) group (n = 153). We evaluated the operative time, intraoperative bleeding, number of fusion vertebrae, correction rate of the main curve, apical vertebral translation, grade of PS perforation (Grade 0: no perforation; Grade 1: < 2 mm; Grade 2: 2‒4 mm; Grade 3: > 4 mm), and accuracy of PS placement. RESULTS: The N group had a significantly longer operative time. There were no significant differences in the clinical results excluding the operative time. The accuracy of PS placement was 93.7%, 91.3%, 93.6%, and 93.5% in the F, 3D + F, LECMD + 3D + F, and N groups, respectively. The Grade 2 perforation rate was 2.5%, 0%, 0.6%, and 0.7% in the F, 3D + F, LECMD + 3D + F, and N groups, respectively. CONCLUSIONS: There were no significant differences in the accuracy of PS placement and clinical results excluding the operative time. The 3D printed model, LECMD, or intraoperative CT navigation would be useful to prevent Grade 2 perforation.

Can prophylactic C4/5 foraminotomy prevent C5 palsy after cervical laminoplasty with and without posterior instrumented fusion with maximal expansion?

OBJECTIVE: To prospectively examine whether laminoplasty with maximal expansion induces C5 palsy, even with prophylactic bilateral C4/5 foraminotomy. METHODS: Thirty-five consecutive patients with cervical myelopathy underwent laminoplasty (n = 19: LP group) or posterior decompression and fusion (n = 16: PDF group) with maximal expansion. Prophylactic bilateral C4/5 foraminotomy was performed alternately in consecutive five patients undergoing each type of surgery. In each type of surgery, the first and third consecutive five patients did not undergo foraminotomy (NF subgroup: 20 patients), while the second and fourth consecutive five patients underwent foraminotomy (F subgroup: 15 patients). The widths between the gutters was equivalent to the diameter of the spinal canal, and an inclination angle of the lamina of approximately 90° was created during laminoplasty. The incidence and severity of postoperative C5 palsy were investigated. Patients with a manual muscle testing score for the deltoid muscle and/or biceps brachii muscle of ≤ 2 were diagnosed with severe palsy. RESULTS: The respective incidences of C5 palsy in the F and NF subgroups were 33% and 20% in the LP group and 50% and 20% in the PDF group. Severe palsy occurred in 67% and 0% of patients who had developed palsy in F and NF subgroups, respectively, in the LP group, and in 100% of patients in the PDF group. Furthermore, 40% of the patients with severe palsy took more than 6 months to recover. CONCLUSIONS: Laminoplasty with maximal expansion induced C5 palsy in both the LP and PDF groups, even with the addition of prophylactic bilateral C4/5 foraminotomy.

Cervical arteriosclerosis is associated with preoperative clinical symptoms in patients with cervical spondylotic myelopathy.

PURPOSE: This study aims to clarify the association between cervical spondylotic myelopathy (CSM) and cervical arteriosclerosis using ultrasonography that comprehensively includes spinal cord stenosis. METHODS: Eighty-two consecutive patients aged over 60 years who underwent spine surgery were divided into those with CSM (n = 31; CSM group) and those with lumbar spinal stenosis without cervical myelopathy (n = 51; LSS group). Maximum spinal cord compression (MSCC) was evaluated for cervical stenosis severity using magnetic resonance (MR) images. The intima-media thickness (IMT) of the common carotid artery (CCA) and pulsatility index (PI) of the bilateral internal carotid artery (ICA) and vertebral artery (VA) were evaluated for cervical arteriosclerosis using pulsed-wave Doppler ultrasonography. Symptom severity was evaluated using the Japanese Orthopaedic Association (JOA) score. Spearman's correlation coefficient was used to determine the relationship between the JOA score and MSCC or IMT and PI in each group. Stepwise multiple linear regression analyses were conducted with the JOA score as a dependent variable and age, sex, body mass index, cervical arteriosclerosis assessment, and MSCC as independent variables. RESULTS: Bilateral IMT and left-side ICA-PI were significantly negatively correlated with JOA scores in the CSM group (Right-CCA-IMT: R = - 0.412, Left-IMT: R = - 0.549, Left-ICA -PI: R = - 0.205, P < 0.05), but not in the LSS group. Multiple linear regression analyses showed that CCA-IMT was the strongest independent factor associated with the preoperative JOA score. CONCLUSIONS: Cervical arteriosclerosis was associated with preoperative clinical symptoms in CSM patients.

Improvement in the results of the simple-foot-tapping test and cross-sectional area of the dural sac in patients with C5 palsy after posterior cervical spine surgery.

INTRODUCTION: The smaller cross-sectional areas of the dural sacs in patients without C5 palsy after posterior cervical spine surgery may lead to less neurological improvement. OBJECTIVES: The aim of this retrospective study was to clarify the differences in the cross-sectional area of the dural sac in the cervical spine and neurological improvement in patients with and without C5 palsy after posterior cervical spinal surgery. METHODS: We retrospectively evaluated the postoperative cross-sectional areas of the dural sacs and neurological outcomes in patients with and without C5 palsy after posterior cervical spine surgery. We compared the postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 on magnetic resonance images between the C5 palsy group (n = 19) and the no-C5 palsy group (n = 84) after posterior cervical spinal surgery 1 year postoperatively. Performance tests, namely, the 10-s grip-and-release test and the 10-s single-foot-tapping (FT) test, were compared between the two groups. RESULTS: Postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 (233.3 mm2 and 226.6 mm2, respectively) in the C5 palsy group were significantly larger (P = 0.0036 and P = 0.0039, respectively) than those (195.0 mm2 and 193.8 mm2, respectively) in the no-C5 palsy group. Postoperative gain in the grip-and-release test was similar between the two groups. Postoperative gain in the FT test (4.9 times) in the C5 palsy group was significantly larger (P = 0.0060) than that (1.8 times) in the no-C5 palsy group. CONCLUSIONS: In the C5 palsy group 1 year after posterior cervical spine surgery, the cross-sectional areas of the dural sac were larger, and the 10-s single FT test improved noticeably.