Risk factor analysis of vertebral fractures requiring surgery in patients with ankylosing spondylitis.

OBJECTIVES: This study aimed to determine the risk factors for vertebral fractures requiring surgery in patients with ankylosing spondylitis (AS). METHODS: We included 60 patients with AS diagnosed by using the modified New York criteria and who were treated in our department from April 2004 to March 2019. We evaluated age, sex, disease duration, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ankylosed sacroiliac joint, bamboo spine, number of ankylosed vertebrae, and treatment (nonsteroidal antiinflammatory drugs (NSAIDs)), prednisolone (PSL), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), spine surgery for vertebral fracture) at the final follow-up of the nonsurgical group and the preoperative follow-up of the surgical group. RESULTS: At the final follow-up, the mean age was 49 years, 46 patients (75%) were male, and the mean disease duration was 27 years. Additionally, 8 (13.3%) and 43 patients (71%) underwent surgical and medical treatments, respectively. The group of surgery for vertebral fracture had significantly higher CRP levels, which was also significantly associated with vertebral fracture surgery by multivariate analysis. CONCLUSIONS: CRP was identified as a risk factor for vertebral fractures requiring surgery. Control of systemic inflammation in patients with AS may reduce the risk of vertebral fractures requiring surgery.

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.

Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.

Risk of transfusion-transmitted infection with severe acute respiratory syndrome coronavirus 2 from blood donors in Japan.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) essentially affects respiratory organs and tissues. SARS-CoV-2 RNAemia is often associated with more severe cases of coronavirus disease 2019 (COVID-19) compared to cases without RNAemia. To determine the impact of the pandemic on transfusion medicine, particularly transfusion-related infection, we examined the frequency of blood donation with RNAemia, the viral RNA (vRNA) concentration, and any possibility of transfusion-transmitted infection (TTI) among transfusion recipients. STUDY DESIGN AND METHODS: vRNA was examined in plasma/serum samples from 496 of 513 blood donors who reported having been infected with SARS-CoV-2 within 2 weeks of donation among a total of ca. 9.9 million blood donations in Japan between January 15, 2020, and December 31, 2021. The clinical course of patients transfused with the blood component containing vRNA was also examined. RESULTS: vRNA was detected in 23 of 496 samples. The median period from blood donation to COVID-19 onset was 1 day in 16 RNAemia-positive donors. Most samples had vRNA concentrations below the limit of quantification. Three patients were transfused with either a packed red blood cell or platelet concentrate that tested positive for vRNA, showing no COVID-19 symptoms and testing negative for vRNA in post-transfusion blood. CONCLUSION: The rate of RNAemia was 4.6% among blood donors who were found to be infected with SARS-CoV-2 shortly after donation, and vRNA concentrations in their donated blood were extremely low. There was no evidence of TTI in the recipients transfused with RNAemia-positive blood components. TTI risk in SARS-CoV-2 is negligible.

Universal nucleic acid donor screening revealed epidemiological features of hepatitis E and prevented transfusion-transmitted infection in Japan.

BACKGROUND: More than 45 cases of transfusion-transmitted hepatitis E virus infection (TT-HEV) have been reported in Japan. Therefore, in 2020, universal individual donation nucleic acid amplification testing (ID-NAT) was implemented for HEV. STUDY DESIGN AND METHODS: We characterized HEV NAT-positive blood donors. The number of new HEV infections and the asymptomatic infection rate were estimated using the HEV NAT-positive rate. HEV RNA quantitation, phylogenetic analysis, and antibody tests were performed, and the residual risk of TT-HEV was assessed based on the lookback study results. RESULTS: A total of 5,075,100 blood donations were screened with ID-NAT during the first year of implementation, among which 2804 (0.055%; males: 0.060%, females: 0.043%) were NAT-positive with regional differences. Approximately 270,000 new HEV infection cases were estimated to occur annually in Japan, with an asymptomatic infection rate of 99.9%. The median HEV RNA concentration, excluding cases below the limit of quantification, was 205 IU/mL. Among the 1113 cases where the genotype could be determined, HEV-3 and HEV-4 accounted for 98.8% (1100) and 1.2% (13), respectively. The maximum duration of HEV viremia, including the pre- and post-ID-NAT window periods, was estimated to be 88.2 days. Within the 3 years since ID-NAT implementation, no confirmed cases of breakthrough TT-HEV were observed. DISCUSSION: Multiple indigenous HEV strains are prevalent in Japan, infecting a significant number of individuals. However, since the implementation of ID-NAT, TT-HEV has been prevented due to the test's high sensitivity.

Evaluation of bone density and skeletal muscle mass after sleeve gastrectomy using computed tomography method.

Introduction: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. Objective: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. Methods: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. Results: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p < 0.01) after surgery. The mean hemoglobin A1c level showed significant improvement in males and females. Serum calcium and phosphorus levels remained unchanged before and after surgery. In CT analysis, HU of the lumbar spine and psoas muscle showed no significant decrease, but PMI showed a significant decrease (p < 0.01). Conclusions: Sleeve gastrectomy could dramatically improve anthropometric measures without causing changes in serum calcium and phosphorus levels. Preoperative and postoperative abdominal CT revealed no significant difference in the bone and psoas muscle density, and the psoas muscle mass was significantly decreased after sleeve gastrectomy.

Deep learning-based automatic-bone-destruction-evaluation system using contextual information from other joints.

BACKGROUND: X-ray images are commonly used to assess the bone destruction of rheumatoid arthritis. The purpose of this study is to propose an automatic-bone-destruction-evaluation system fully utilizing deep neural networks (DNN). This system detects all target joints of the modified Sharp/van der Heijde score (SHS) from a hand X-ray image. It then classifies every target joint as intact (SHS = 0) or non-intact (SHS ≥ 1). METHODS: We used 226 hand X-ray images of 40 rheumatoid arthritis patients. As for detection, we used a DNN model called DeepLabCut. As for classification, we built four classification models that classify the detected joint as intact or non-intact. The first model classifies each joint independently, whereas the second model does it while comparing the same contralateral joint. The third model compares the same joint group (e.g., the proximal interphalangeal joints) of one hand and the fourth model compares the same joint group of both hands. We evaluated DeepLabCut's detection performance and classification models' performances. The classification models' performances were compared to three orthopedic surgeons. RESULTS: Detection rates for all the target joints were 98.0% and 97.3% for erosion and joint space narrowing (JSN). Among the four classification models, the model that compares the same contralateral joint showed the best F-measure (0.70, 0.81) and area under the curve of the precision-recall curve (PR-AUC) (0.73, 0.85) regarding erosion and JSN. As for erosion, the F-measure and PR-AUC of this model were better than the best of the orthopedic surgeons. CONCLUSIONS: The proposed system was useful. All the target joints were detected with high accuracy. The classification model that compared the same contralateral joint showed better performance than the orthopedic surgeons regarding erosion.

Risk factor analysis of perioperative complications in patients with rheumatoid arthritis undergoing primary cervical spine surgery.

BACKGROUND: Rheumatoid arthritis (RA) often causes cervical spine lesions as the disease condition progresses, which induce occipital neuralgia or cervical myelopathy requiring surgical interventions. Meanwhile, patients with RA are susceptible to infection or other complications in the perioperative period because they frequently have comorbidities and use immunosuppressive medications. However, the risk factors or characteristics of patients with RA who experience perioperative complications after cervical spine surgery remain unknown. A risk factor analysis of perioperative complications in patients with RA who underwent primary cervical spine surgery was conducted in the present study. METHODS: A total of 139 patients with RA who underwent primary cervical spine surgery from January 2001 to March 2020 were retrospectively investigated. Age and height, weight, serum albumin, serum C-reactive protein, American Society of Anesthesiologists Physical Status (ASA-PS), Charlson comorbidity index, medications used, cervical spine lesion, surgery time, bleeding volume, and procedures were collected from medical records to compare the patients with complications to those without complications after surgery. The risk factors for perioperative complications were assessed by univariate and multivariate logistic regression analysis. RESULTS: Twenty-eight patients (20.1%) had perioperative complications. Perioperative complications were significantly associated with the following factors [data presented as odds ratio]: lower height [0.928, p=0.007], higher ASA-PS [2.296, p=0.048], longer operation time [1.013, p=0.003], more bleeding volume [1.004, p=0.04], higher rates of vertical subluxation [2.914, p=0.015] and subaxial subluxation (SAS) [2.507, p=0.036], occipito-cervical (OC) fusion [3.438, p=0.023], and occipito-cervical/thoracic (long) fusion [8.021, p=0.002] in univariate analyses. In multivariate analyses, lower height [0.915, p=0.005], higher ASA-PS [2.622, p=0.045] and long fusion [7.289, p=0.008] remained risk factors. High-dose prednisolone use [1.247, p=0.028], SAS [6.413, p=0.018], OC fusion [17.93, p=0.034], and long fusion [108.1, p<0.001] were associated with severe complications. CONCLUSIONS: ASA-PS and long fusion could be indicators predicting perioperative complications in patients with RA after cervical spine surgery. In addition, cervical spine lesions requiring OC fusion or long fusion and high-dose prednisolone use were suggested to be risk factors for increasing severe complications.

Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: results from the multicenter observational cohort study, FRANK Registry.

BACKGROUND: To further improve rheumatoid arthritis (RA) treatment, it is necessary to understand each RA patient's satisfaction and to identify the factors affecting their satisfaction. Despite the rise in medical costs for RA, little is known about the factors that influence patient satisfaction with the cost of treatment in RA patients. METHODS: This is a multicenter observational study of Japanese RA patients from the FRANK Registry with data analyzed from March 2017 to August 2020. We collected data on demographic characteristics, clinical data, quality of life which was evaluated using the EuroQol 5-dimensional questionnaire (EQ5D), and patient satisfaction. The four categories of patient satisfaction were evaluated individually (i.e., cost, treatment efficacy, activities of daily living [ADL], and global treatment satisfaction). We analyzed the factors that affected each patient's satisfaction, such as age, sex, EQ5D, disease duration, disease activity, and treatment. RESULTS: This study included 2235 RA outpatients (406 males, 1829 females). In RA patients, "very satisfied" and "satisfied" were given for nearly half of each satisfaction aspect (cost 49%; efficacy 72%; ADL 58%; global treatment 66%) at the time of the initial registration. To investigate the factors influencing each satisfaction, multivariate analysis has revealed that the use of b/tsDMARDs increased satisfaction of treatment effect (odds ratio [OR] 0.66) and ADL (OR 0.78) but decreased cost satisfaction (OR 2.21). Age (50-64 years; OR 0.91; 65-74 years, 0.55: ≥ 75 years, 0.35), female (OR 0.81), and history of musculoskeletal surgery (OR 0.60) all increased cost satisfaction. Patients with lower disease activity and higher EQ5D scores had higher levels of satisfaction in all areas. CONCLUSIONS: In this study, patient satisfaction in terms of cost, treatment effect, ADL, and overall treatment was generally higher, but some patients were dissatisfied. The cost of satisfaction increased with age and a history of musculoskeletal surgery, while it decreased with a lower EQ5D score and the use of b/tsDMARDs.

Autoreactivity of Peripheral Helper T Cells in the Joints of Rheumatoid Arthritis.

Autoreactive CD4 T cells are thought to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). Recently, a subset of CD4 T cells that express high levels of programmed death-1 (PD-1) but are distinct from follicular helper T cells have been identified in the joints of RA patients and named peripheral helper T (Tph) cells. Because PD-1 is expressed on T cells chronically stimulated with the Ags, we tested a hypothesis that Tph cells are the pathogenic autoreactive CD4 T cells in RA. We found that human Tph cells in RA joints produce proinflammatory effector cytokines, including IFN-γ, TNF-α, and GM-CSF, in addition to B cell-helping cytokines, such as IL-21 and CXCL13. Flow cytometric analysis showed different bias of TCR Vß usage between PD-1high Tph cells and PD-1low/neg CD4 T cells, including Th1 cells, in the joint or memory CD4 T cells in the peripheral blood, whereas there was little difference between the latter two subsets. In line with this, deep sequencing of TCR demonstrated an overlap of expanded clones between peripheral blood memory CD4 T cells and PD-1low/neg CD4 T cells but not Tph cells in the joint. Interestingly, Tph cells preferentially exhibited autologous MLR in vitro, which required recognition of self-MHC class II and was pronounced by blocking PD-1 signaling. Taken together, these results suggest that Tph cells are the pathogenic autoreactive CD4 T cells in RA, which expand locally in the joints and are regulated by PD-1 signaling.

Surgical Outcomes of Minimally Invasive Stabilization for Spinal Fractures in Patients with Ankylosing Spinal Disorders.

STUDY DESIGN: A retrospective study. PURPOSE: To evaluate the clinical and radiological outcomes of ankylosing spinal disorder (ASD) patients with spinal fractures treated by minimally invasive stabilization (MISt) using percutaneous pedicle screws (PPSs). OVERVIEW OF LITERATURE: ASDs, such as ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), increase susceptibility to spinal fractures because of extremely decreased spinal flexibility. Such fractures tend to be unstable and, consequently, should be treated with multiple-segmental internal fixation. However, conventional internal fixation procedures can severely damage the soft tissue, resulting in severe hemorrhage. Therefore, MISt is the preferred approach to treat spinal fractures in ASD patients. METHODS: Nine ASD patients (four males and five females; three AS and six DISH patients) with spinal fractures who were treated by MISt using PPSs, were reviewed from April 2009 to August 2016. One patient died of aspiration pneumonia during follow-up (FU), and the remaining eight patients underwent clinical and radiological evaluation. RESULTS: The mean age at surgery was 79.6 years (range, 68-95 years). The mean duration of postoperative FU was 14.2 months (range, 3-30 months). All treated fractures were anterior and posterior element injuries with distraction. Three patients presented delayed onset preoperative neurological deficit following trauma. The mean operation time was 179.6 minutes (range, 92-340 minutes). The mean hemorrhage was 103.6 mL (range, unquantifiable to 480 mL). Radiological evaluations at FU showed preservation of the acceptable postoperative correction of the fractured vertebra, as there were no re-collapses of the fractured vertebrae during FU. CONCLUSIONS: ASD patients must be acknowledged as highly susceptible to unstable spinal fractures, even after relatively mild trauma. MISt using PPSs may be an effective treatment for spinal fractures in such patients.

Clinical and Radiological Study Focused on Relief of Low Back Pain After Decompression Surgery in Selected Patients With Lumbar Spinal Stenosis Associated With Grade I Degenerative Spondylolisthesis.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of the present study was to identify the clinical and radiological features of low back pain (LBP) that was relieved after decompression alone of lumbar spinal stenosis (LSS) associated with grade I lumbar degenerative spondylolisthesis (LDS). SUMMARY OF BACKGROUND DATA: Although decompression and fusion are generally the recommended surgical treatments of LDS, several authors have reported that some patients with LDS could obtain good clinical results including relief from LBP by decompression alone. The pathogenesis of relief from LBP after decompression is, however, not known. METHODS: Forty patients with LSS associated with grade I LDS, who underwent a minimally invasive surgical-decompression were enrolled in the present study. All patients complained preoperatively of predominantly leg-related symptoms and LBP (≥ 4 points on Numeric Rating Scale). Clinical and radiological assessments were performed 1 year after surgery (a relief of LBP: Numeric Rating Scale reduction ≥3 points and valuation ≤3 points) and at the last follow-up. We conducted a comparative study between patient groups with and without the relief from LBP (groups R and N, respectively). RESULTS: Twenty-nine patients were distributed to group R and the remaining 11 patients to group N. Preoperatively, there was a significant difference between the two groups for age and radiographic flexibility for lumbar extension. Postoperatively, there was a positive correlation between improvement in both LBP and leg symptoms. The clinical outcomes of group R were significantly better than those of group N throughout follow-up period (mean 37 mo). In group R, sagittal lumbopelvic radiographic parameters improved significantly after surgery. CONCLUSION: Although the causes of LBP are varied in each patients, our results show that concomitant LSS itself might cause LBP in some patients with grade I LDS, because it involves impingement of the neural tissue and discordant sagittal lumbopelvic alignment. LEVEL OF EVIDENCE: 3.