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Background Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. Methods We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. Results Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine ( p = 0.009), uric acid ( p = 0.024), and tyrosine ( p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA ( p < 0.001, area under the curve 0.714, odds ratio 3.7). Conclusion Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

Purpose There are few reports regarding the association between the neutrophil–lymphocyte ratio (NLR), uric acid, and the development of postoperative delirium (POD) in patients who are undergoing spine surgeries. We investigated the associations between the NLR, uric acid as a natural antioxidant, and POD in elderly patients undergoing degenerative spine surgery. Patients and methods This was a single-center, observational, and retrospective study conducted in Japan. We enrolled 410 patients who underwent degenerative spine surgery. POD was diagnosed after the surgeries by psychiatrists, based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). We performed a multivariable logistic regression analysis to clarify whether the NLR and uric acid values were associated with the development of POD in the patients. Results 129 of the 410 patients were excluded from the analysis. Of the 281 patients (137 females, 144 males), 32 patients (11.4%) were diagnosed with POD. The multivariable logistic regression analysis revealed that the preoperative uric acid level (adjusted odds ratio [aOR]: 0.67, 95% confidence interval [CI]: 0.49–0.90, p  = 0.008) and age (aOR: 1.09, 95% CI: 1.02–1.16, p  = 0.008) were significantly associated with POD. The preoperative NLR (aOR: 0.82, 95% CI: 0.60–1.13, p  = 0.227) and antihyperuricemic medication (aOR: 0.97, 95% CI: 0.24–3.82, p  = 0.959) were not significantly associated with POD. Conclusion Our results demonstrated that in elderly patients undergoing degenerative spine surgery, the preoperative NLR was not significantly associated with POD, but a lower preoperative uric acid value was an independent risk factor for developing POD. Uric acid could have a neuroprotective impact on POD in patients with degenerative spine diseases.

PurposeThis study aims to clarify the association between cervical spondylotic myelopathy (CSM) and cervical arteriosclerosis using ultrasonography that comprehensively includes spinal cord stenosis.MethodsEighty-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.ResultsBilateral 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.ConclusionsCervical arteriosclerosis was associated with preoperative clinical symptoms in CSM patients.

PurposeThis study aimed to evaluate the association between cervical atherosclerosis on Doppler ultrasonography and postoperative delirium (POD) in patients undergoing spinal surgery.MethodsIn this retrospective observational study using prospectively collected data, 295 consecutive patients aged > 50 years underwent spine surgery at a single institution between March 2015 and February 2021. Cervical atherosclerosis was defined as the intima-media thickness (IMT) of the common carotid artery (CCA) being ≥ 1.1 mm on pulsed-wave Doppler ultrasonography. Univariate and multivariate logistic regression analyses were performed with the prevalence of postoperative delirium as a dependent variable. Age, sex, body mass index, medical history, American Society of Anesthesiologists Physical Status (ASA-PS), CHADS2 score (an assessment score for stroke), instrumentation, duration of surgery, blood loss, and cervical arteriosclerosis were the independent variables.ResultsTwenty-seven patients of 295 (9.2%) developed delirium postoperatively. Forty-one (13.9%) of the 295 patients had cervical atherosclerosis. Their univariate analyses showed that age (P = 0.001), hypertension (P = 0.016), cancer (P = 0.046), antiplatelet agent use (P < 0.001), ASA-PS ≥ 3 (P < 0.001), CHADS2 score (P < 0.001), cervical atherosclerosis (P = 0.008), and right CCA-IMT (P = 0.007) were significantly associated with POD. However, multivariate logistic regression analyses showed older age (odds ratio [OR], 1.109; 95% confidence interval [CI] 1.035–1.188; P = 0.03) and antiplatelet agent use (OR, 3.472; 95% CI 1.221–9.870; P = 0.020) to be significantly associated with POD.ConclusionsThere was a significant association between POD and the prevalence of cervical atherosclerosis using the univariate logistic regression analysis. Furthermore, multivariate logistic regression analyses showed that older age and antiplatelet agent use were independently associated with POD.

It has been reported that female rats have a sex-related advantage in functional recovery and neuroprotection after spinal cord injury (SCI). However, the association between anxiety and neurological function after SCI in female and male rats remains unclear. The aim of this study was to examine sex-related differences in anxiety and neurological dysfunction after SCI in adult C57/BL6 male and female mice. After laminectomy at the 10th thoracic level, a contusive SCI was induced. The sham group received only a T10 laminectomy. Behavior testing (anxiety, motor/sensory function) was performed for 6 weeks after SCI. The spinal cord and preserved myelinated areas at the epicenter were histologically evaluated. Correlations between anxiety and motor/sensory function or histological parameters were analyzed using the Spearman correlation coefficient. Female and male mice showed significantly higher anxiety-like behaviors after SCI than before SCI. Anxiousness was significantly higher in female mice than in male mice after SCI. There was no significant difference in motor/sensory functions and histological features between the two groups. Anxiety-like behaviors were significantly correlated with sensory function at 2 weeks after SCI in female mice and with motor function at 2, 4, and 6 weeks after SCI in male mice. Anxiety-like behaviors were not significantly correlated with the spinal cord area at the epicenter in female and male mice. Our results revealed that female mice became more anxious than male mice after SCI. Anxiety-like behavior after SCI may be associated with functional recovery, and improving anxiety may affect functional recovery after injury.

Lumbar degenerative disease and dementia are increasing in super-aging societies and are both related to physical dysfunction and pain. However, the relationship between these diseases remains unclear. This cross-sectional study aimed to investigate the comorbidity rates of lumbar spinal canal stenosis (LSS) and mild cognitive impairment (MCI) and clarify the association between LSS presence, lumbar symptoms, and quality of life (QOL) related to low back pain and cognitive impairment in the Japanese population. We enrolled 336 participants (men 124; women 212; mean age 72.2 years) from a medical checkup program. LSS was diagnosed using a self-administered questionnaire, and lumbar symptoms were evaluated using the visual analog scale (low back pain, and pain and numbness of the lower limb). QOL related to low back pain was evaluated using the Japanese Orthopedic Association Back-Pain Evaluation Questionnaire (JOABPEQ: pain, and lumbar, and gait function). Radiological lumbar degeneration was classified using Kellgren-Lawrence grading and lateral radiographs of the lumbar spine. Cognitive function was measured using the Mini Mental State Examination (MMSE), and MCI was defined by a summary score of MMSE ≤27. Logistic and multiple linear regression analyses were performed to analyze the association between MCI, summary score of MMSE, and lumbar degenerative disease. The comorbidity rate of MCI and LSS was 2.1%, and the rate of MCI was 41% in participants with LSS. Lumbar function in JOABPEQ was associated with MCI. The presence of LSS and lumbar function in JOABPEQ were associated with MMSE. Over one-third of the people with LSS had MCI. The presence of LSS and deterioration of QOL due to low back pain were related to cognitive impairment. We recommend evaluating cognitive function for patients with LSS because the rate of MCI was high in LSS participants.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stem cells that can be isolated based on stage-specific embryonic antigen-3 (SSEA-3), a pluripotent stem cell-surface marker. However, their capacities for survival, neurotrophic factor secretion, and neuronal and glial differentiation are unclear in rodents. Here we analyzed mouse adipose tissue-derived Muse cells in vitro. We collected mesenchymal stem cells (MSCs) from C57BL/6 J mouse adipose tissue and separated SSEA-3+, namely Muse cells, and SSEA-3–, non-Muse cells, to assess self-renewability; pluripotency marker expression (Nanog, Oct3/4, Sox2, and SSEA-3); spontaneous differentiation into endodermal, mesodermal, and ectodermal lineages; and neural differentiation capabilities under cytokine induction. Neurally differentiated Muse and non-Muse cell functions were assessed by calcium imaging. Antioxidant ability was measured to assess survival under oxidative stress. Brain-derived neurotrophic factor (BDNF), vascular endothelial cell growth factor (VEGF), and hepatocyte growth factor (HGF) secretion were analyzed in enzyme-linked immunosorbent assays. SSEA-3+ Muse cells (6.3 ± 1.9% of mouse adipose-MSCs), but not non-Muse cells, exhibited self-renewability, spontaneous differentiation into the three germ layers, and differentiation into cells positive for Tuj-1 (27 ± 0.9%), O4 (17 ± 3.4%), or GFAP (23 ± 1.3%) under cytokine induction. Neurally differentiated Muse cells responded to KCl depolarization with greater increases in cytoplasmic Ca2+ levels than non-Muse cells. Cell survival under oxidative stress was significantly higher in Muse cells (50 ± 2.7%) versus non-Muse cells (22 ± 2.8%). Muse cells secreted significantly more BDNF, VEGF, and HGF (273 ± 12, 1479 ± 7.5, and 6591 ± 1216 pg/mL, respectively) than non-Muse cells (133 ± 4.0, 1165 ± 20, and 2383 ± 540 pg/mL, respectively). Mouse Muse cells were isolated and characterized for the first time. Muse cells showed greater pluripotency-like characteristics, survival, neurotrophic factor secretion, and neuronal and glial-differentiation capacities than non-Muse cells, indicating that they may have better neural-regeneration potential.

This study aimed to investigate the relationship between the cross-sectional area of the dural sac (DCSA) and lower urinary tract symptoms (LUTS). This study included 270 Japanese participants from a community health check-up in 2016. Overactive bladder (OAB) was diagnosed during the assessment of LUTS. The smallest DCSA of each participant was defined as the minimum DCSA (mDCSA). The cutoff size of the mDCSA in OAB was evaluated using receiver operating characteristic analysis. Multiple logistic regression analyses were performed to identify the independent risk factors for OAB, and a scoring system was developed for estimating these. The prevalence of OAB was 11.1%. Age and low back pain visual analogue scale (LBP VAS) scores were significantly higher, and the mean mDCSA was significantly lower in participants with OAB than in those without. The cutoff size of mDCSA in OAB was 69 mm 2 . There were significant correlations between OAB and age, LBP VAS score, and mDCSA<70 mm 2 . Lumbar spinal stenosis (LSS) should be considered a cause of LUTS when mDCSA is <69 mm 2 . Assessing the mDCSA with age and LBP VAS score was more valuable in detecting LUTS in LSS than the mDCSA alone.

BackgroundJapanese medical schools have made advances in terms of English and Medical English teaching in the past decade, in keeping with their importance in medical communication and research. English skills and proficiency levels differ across different institutions due to the variable adoption of general teaching requirements. A limitation in assessing English proficiency among Japanese medical students continues to exist due to the lack of standardized testing requirements.MethodsA new questionnaire was developed by faculty members and medical students. Areas of importance were: demographics, proficiency and confidence ratings, history of learning and usage, duration of usage, perceived importance, and improvement goals. The final draft of the constructed questionnaire contained 21 questions in total. The questionnaire was administered over a three-month period in incremental order of enrollment through a digital online platform.ResultsA total of 133 students, 64 (48.1%) males and 69 (51.9%) females, participated. The average age was 23.7 ± 4.8 years. Based on an incremental Likert scale, respondents rated themselves as 1.0 ± 0.8 for English proficiency and 0.5 ± 0.7 for Medical English proficiency. The confidence level for English medical discussions was 0.2 ± 0.6 on a similar scale. Students on average attended 18.0 ± 30.0 classes per year and presented medical materials in English around 1.7 ± 1.7 times in total. The English language was used for 2.1 ± 6.3 hours per week in personal settings and 0.5 ± 1.7 hours per week in professional settings.ConclusionsThe proposed questionnaire was able to give valuable information about language skills and proficiency levels, but would require an incentive for improved participation. The pilot analysis showed that English and Medical English proficiency levels remain low with limited opportunities for using English in some areas within Japan. It may be beneficial to provide Japanese medical students with more occasions where they can use or practice their English skills.

The number of total hip arthroplasty and bipolar hemiarthroplasty is increasing because of their good clinical outcomes and the aging population. Consequently, the incidence of periprosthetic femoral fractures (PFFs) is expected to increase in older patients with osteoporosis. Surgery is the first choice of treatment for PFF, except in Vancouver Type A fractures. However, surgical treatment of PFF, including open reduction and internal fixation (ORIF) and revision arthroplasty, is highly invasive, and high mortality rates have been reported. The indication for ORIF for PFF in very elderly patients at a high risk of complications remains controversial, and postoperative outcomes are uncertain. This study aimed to evaluate the postoperative outcomes of ORIF for PFF in elderly patients. We retrospectively analyzed four females with a mean age of 90.7 years (91-92 years) who underwent ORIF for PFF at our institution from September 2014 to January 2023. No cases of American Society of Anesthesiologists (ASA) grade 3 or higher were found. Three patients were classified as Vancouver Type B1, and one was classified as Vancouver Type C. Cementless stems were used in primary surgeries in all cases. To measure clinical outcomes, we investigated the patient's walking ability at 30 days, three months postoperatively, and the final follow-up. Mortality was assessed during the follow-up period. One patient could walk without walking aids preoperatively, two used a walking stick, and one used a walker. All patients remained hospitalized and underwent gait training with a walker at 30 days follow-up; however, at three months postoperatively and the final follow-up, no patient was unable to walk. No deaths occurred within one month of surgery. Three deaths occurred during follow-up: one within six months, one within one year, and one within five years of surgery. The postoperative ORIF results for PFF in patients aged > 90 years showed no fatal perioperative complications and low mortality within 30 days postoperatively. These results suggest that ORIF for PFF can be considered for elderly patients if the preoperative ASA grade is relatively low.