Medication-based profiling of older orthopedic patients: a multicenter cross-sectional study.

BACKGROUND: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. METHODS: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. RESULTS: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11-1.44] and 1.12 [CI: 1.00-1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14-56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05-1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. CONCLUSIONS: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

NK and T-lymphocyte Kinetics Predict Outcome in Myeloma Patients Treated With Elotuzumab, Lenalidomide Plus Dexamethasone.

Background/Aim: Elotuzumab, an anti-SLAMF7 monoclonal antibody, can enhance immune activity via elevated antibody-dependent cellular cytotoxicity and reduced SLAMF7+CD8+CD57+ regulatory T-cells (Tregs). This multicenter observational study investigated the kinetics of lymphocytes in myeloma patients treated with elotuzumab, lenalidomide, and dexamethasone (ERd) by two-color flow cytometry using peripheral blood samples. Patients and Methods: Twenty-one patients were included in this study. The median duration of ERd was 22.6 months, and the cutoff time for long-duration ERd was two years. Results: The CD2+CD16+ and CD16+CD57- NK cells were significantly increased over time in the long-duration ERd group compared to those in the short-duration ERd group (p=0.035 and p<0.001). The CD8+ and CD16-CD57+ lymphocytes, identified as low-activity NK cells or SLAMF7+ Tregs, were significantly increased in the patients whose ERd outcome was progressive disease (PD) compared to those in the non-PD group (p=0.023 and p<0.001). The mean CD4/CD8 ratio and CD19+ lymphocyte counts in the long-duration ERd group were significantly lower than those in the short-duration ERd group, although the kinetics of them did not change over time (p=0.016 and p=0.011). When the cutoff value of CD4/CD8 ratio was 0.792 according to ROC curves, the two-year time to next treatment (TTNT) in the low CD4/CD8 group was significantly longer than that in the high CD4/CD8 group (80.0% vs. 15.0%, p=0.024). Conclusion: The change in NK cells and CD8+ Tregs predicted long-duration ERd and PD, and maintaining low CD4/8 ratio predicted long TTNT, suggesting that these lymphocyte fractions might be biomarkers for a durable therapeutic effect of ERd in myeloma patients.

Cerebrospinal Fluid Dynamics Analysis Using Time-Spatial Labeling Inversion Pulse (Time-SLIP) Magnetic Resonance Imaging in Mice.

Background/Objectives: Abnormalities in cerebrospinal fluid (CSF) dynamics cause diverse conditions, such as hydrocephalus, but the underlying mechanism is still unknown. Methods to study CSF dynamics in small animals have not been established due to the lack of an evaluation system. Therefore, the purpose of this research study is to establish the time-spatial labeling inversion pulse (Time-SLIP) MRI technique for the evaluation of CSF dynamics in mice. Methods: We performed the Time-SLIP technique on 10 wild-type mice and 20 Tiptoe-walking Yoshimura (TWY) mice, a mouse model of ossification of the posterior longitudinal ligament (OPLL). We defined the stir distance as the distance of CSF stirring and calculated the mean ± standard deviation. The intraclass correlation coefficient of intraobserver reliability was also calculated. Furthermore, in TWY mice, the correlation coefficient between stir distance and canal stenosis ratio (CSR) was calculated. Results: The stir distance was significantly lower in TWY mice at 12 weeks and 17 weeks of age (1.20 ± 0.16, 1.21 ± 0.06, and 1.21 ± 0.15 mm at 12 weeks and 1.32 ± 0.21, 1.28 ± 0.23, and 1.38 ± 0.31 mm at 17 weeks for examiners A, B, and C). The intrarater reliability of the three examiners was excellent (>0.90) and there was a strongly negative correlation between stir distance and CSR in TWY mice (>-0.80). Conclusions: In this study, we established the Time-SLIP technique in experimental mice. This technique allows for a better understanding of CSF dynamics in small laboratory animals.

Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain.

BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022. RESULTS: The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS. CONCLUSION: Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.

Extra-Articular Stabilization for the Treatment of Recurrent Sternoclavicular Joint Instability: A Report of Two Cases.

CASE: A 22-year-old man and a 14-year-old adolescent boy, who exhibited moderate general joint laxity, experienced recurrent sternoclavicular joint instability without traumatic events. The patients were successfully treated with extra-articular stabilization using autologous tendon grafts without surgical exposure of the sternoclavicular joint. CONCLUSION: Atraumatic instability of the sternoclavicular joint is rare but often results in recurrent instability accompanied by discomfort, pain, and limitations in activities. Extra-articular stabilization, which reinforces the anterior capsule of the sternoclavicular joint and prevents anterior displacement of the proximal clavicle at the elevated arm position, could be a viable surgical option for this pathological condition.

The significance of cerebrospinal fluid dynamics in adolescent idiopathic scoliosis using time-SLIP MRI.

Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = - 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = - 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression.

Dysregulation of Inflammatory Pathways in Adult Spinal Deformity Patients with Frailty.

Background/Objectives: An important aspect of the pathophysiology of frailty seems to be the dysregulation of inflammatory pathways and the coagulation system. However, an objective assessment of the impact of frailty on the recovery from surgery is not fully studied. This study sought to assess how frailty affects the recovery of adult spinal deformity (ASD) surgery using blood biomarkers. Methods: 153 consecutive ASD patients (age 64 ± 10 yr, 93% female) who had corrective spine surgery in a single institution and reached 2y f/u were included. The subjects were stratified by frailty using the modified frailty index-11 (robust [R] group or prefrail and frail [F] group). Results of commonly employed laboratory tests at baseline, 1, 3, 7, and 14 post-operative days (POD) were compared. Further comparison was performed in propensity-score matched-39 paired patients between the groups by age, curve type, and baseline alignment. A correlation between HRQOLs, major complications, and biomarkers was performed. Results: Among the propensity-score matched groups, CRP was significantly elevated in the F group at POD1,3(POD1; 5.3 ± 3.1 vs. 7.9 ± 4.7 p = 0.02, POD3; 6.6 ± 4.6 vs. 8.9 ± 5.2 p = 0.02). Transaminase was also elevated in the F group at POD3(ASD: 36 ± 15 vs. 51 ± 58 U/L, p = 0.03, ALT: 32 ± 16 vs. 47 ± 55 U/L, p = 0.04). Interestingly, moderate correlation was observed between transaminase at POD1 and 2 y SRS22 (AST; function r = -0.37, mental health r = -0.39, satisfaction -0.28, total r = -0.40, ALT; function r = -0.37, satisfaction -0.34, total r = -0.39). Conclusions: Frailty affected the serum CRP and transaminase differently following ASD surgery. Transaminase at early POD was correlated with 2 y HRQOLs. These findings support the hypothesis that there is a specific physiological basis to the frailty that is characterized in part by increased inflammation and that these physiological differences persist.

Influence of slippage reduction and correction of lumbosacral kyphosis by single-level posterior lumbar interbody fusion on spinal alignment in patients with dysplastic spondylolisthesis.

PURPOSE: To investigate the influence of slippage reduction and correction of lumbosacral kyphosis by L5-S1 single-level posterior lumbar interbody fusion (PLIF) on spinal alignment and clinical outcomes including postoperative complications in patients with dysplastic spondylolisthesis (DS). METHODS: Twenty consecutive patients with symptomatic and severe DS who underwent L5-S1 single-level PLIF with a minimum of 2 years of follow-up after surgery were included. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) and visual analog scale (VAS) scores for low back and leg pain obtained on preoperative and postoperative examinations. Postoperative instrumentation failure and L5 radiculopathy were also evaluated. The preoperative and postoperative spinopelvic parameters were measured. RESULTS: The JOA score significantly improved from 21.5 ± 4.8 (preoperative) to 27.0 ± 2.5 (postoperative), with a mean recovery rate of 75.0% ± 30.4%. The VAS score for low back pain significantly improved from 44.5 ± 30.1 (preoperative) to 11.5 ± 15.9 (postoperative), and that for leg pain significantly improved from 31.0 ± 33.2 (preoperative) to 5.0 ± 10.2 (postoperative). The slip percentage (% slip) significantly improved from 59.6% ± 13.5% (preoperative) to 25.2% ± 15.0% (postoperative). The lumbosacral angle (LSA) significantly improved from 12.3° ± 9.5° (preoperative) to 1.0° ± 4.9° (postoperative). L5-S1 PLIF led to significant improvement of lumbar lordosis (from 52.0° ± 15.9° to 59.7° ± 8.0°) and pelvic incidence - lumbar lordosis mismatch (from 23.9° ± 20.6° to 13.3° ± 10.0°). Correction of lumbosacral kyphosis had a significant positive correlation with postoperative pelvic tilt (PT) (r = 0.50, P = 0.02), while postoperative % slip did not have a significant correlation with postoperative PT. CONCLUSIONS: L5-S1 PLIF for DS provided good clinical outcomes. Correction of lumbosacral kyphosis had a positive impact on regaining ideal spinopelvic balance and may be beneficial in the setting of treating DS.

Bilateral Upper Arm Granulomas Induced by Leuprorelin Acetate Injection Mimicking Malignant Soft Tissue Tumors: A Case Report.

Leuprorelin acetate is a common anticancer medication used for prostate cancer treatment. One of the local adverse reactions after leuprorelin injection is the development of reactive granulomas, typically presenting as subcutaneous nodules. In this case report, we describe a 73-year-old patient with prostate cancer who developed unusually large sized intramuscular reactive granulomas, which mimicked malignant soft tissue tumors. The patient, who had been receiving leuprorelin acetate treatment for the past 12 months, noticed painful masses in both upper arms. Based on the findings of magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography, a diagnosis of malignant soft tissue tumor was strongly suggested. However, further investigation through needle biopsy ultimately led us to the final diagnosis of reactive granuloma. The masses spontaneously resolved after discontinuation of leuprorelin injection. While reactive granulomas after leuprorelin injections are not rare, intramuscular cases are relatively uncommon. Despite using imaging studies as a rational initial approach in the diagnostic process, as we did in our case, their results turned out to be indistinguishable from those of malignant soft tissue tumors, thus highlighting the importance of pathological examination in confirming diagnosis, especially when a patient presents with atypical clinical manifestations.

Pelvic Incidence As a Predictor of Proximal Junctional Kyphosis in Patients with Lenke type 5 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To evaluate the relationship between pelvic incidence (PI) and proximal junctional kyphosis (PJK) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although PJK is a common complication of sagittal malalignment after posterior correction and fusion surgery (PSF), few studies have assessed its risk factors. The significance of pelvic morphology in relation to PJK has been suggested but remains unclear in Lenke type 5 AIS patients. METHODS: A total of 92 patients with Lenke type 5 AIS who underwent selective thoracolumbar PSF with a minimum follow-up of two years were included. Patients were divided into PJK and non-PJK groups based on postoperative radiographs. The influence of PI on PJK occurrence was evaluated through binary logistic analysis. Subgroup analysis was performed based on the PI value (low PI,<45°; high PI, ≥ 45°) to identify factors affecting PJK occurrence. RESULTS: PJK was observed in 17.4% of the whole cohort. Binary logistic regression analysis identified low PI and large TL/L curve as a risk factor for PJK (PI, odds ratio, 0.933; TL/L curve, odds ratio, 1.080). Subgroup analysis showed that the postoperative increase in the upper instrumented vertebra slope in PJK cases was comparable in both the low and high PI groups. Meanwhile, lordotic changes in the fused area in the PJK cases were observed only in the low PI group. No difference in the Scoliosis Research Society 22 scores were observed between the two groups. CONCLUSION: From this study a low PI was identified as a risk factor for the occurrence of PJK in Lenke type 5 AIS patients. The occurrence of PJK is influenced by lordotic changes in the fused area and the limited compensatory capacity of the pelvis in patients with a low PI.

Phase II Trial of Romidepsin as Consolidation Therapy after Gemcitabine, Dexamethasone, and Cisplatin in Elderly Transplant-Ineligible Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma.

Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. The objective of this study was to characterize the safety and efficacy of romidepsin as consolidation therapy after gemcitabine, dexamethasone, and cisplatin (GDP) therapy (GDPR). This study of patients treated between March 2019 and March 2021 was registered with the Japan Registry of Clinical Trials (registration number: jRCT0000000519). If complete response, partial response, or stable disease was confirmed after 2-4 GDP cycles, romidepsin was administered every 4 weeks for 1 year. Seven patients with relapsed/refractory (R/R) PTCL (T-follicular helper phenotype [n = 1] and angioimmunoblastic T-cell lymphoma [n = 6]) were included in this prospective study (PTCL-GDPR). After a median follow-up of 34 months of patients in PTCL-GDPR, the 2-year overall survival rate was 71%, and the overall response rate after treatment was 57%. Common adverse events in patients with PTCL-GDPR included hematological toxicities such as neutropenia, which improved with supportive treatment. There were no treatment-related mortalities. GDPR might be safe and effective in elderly transplant-ineligible patients with R/R PTCL; however, further investigation is required.

Bezafibrate attenuates immobilization-induced muscle atrophy in mice.

Muscle atrophy due to fragility fractures or frailty worsens not only activity of daily living and healthy life expectancy, but decreases life expectancy. Although several therapeutic agents for muscle atrophy have been investigated, none is yet in clinical use. Here we report that bezafibrate, a drug used to treat hyperlipidemia, can reduce immobilization-induced muscle atrophy in mice. Specifically, we used a drug repositioning approach to screen 144 drugs already utilized clinically for their ability to inhibit serum starvation-induced elevation of Atrogin-1, a factor related to muscle atrophy, in myotubes in vitro. Two candidates were selected, and here we demonstrate that one of them, bezafibrate, significantly reduced muscle atrophy in an in vivo model of muscle atrophy induced by leg immobilization. In gastrocnemius muscle, immobilization reduced muscle weight by an average of ~ 17.2%, and bezafibrate treatment prevented ~ 40.5% of that atrophy. In vitro, bezafibrate significantly inhibited expression of the inflammatory cytokine Tnfa in lipopolysaccharide-stimulated RAW264.7 cells, a murine macrophage line. Finally, we show that expression of Tnfa and IL-1b is induced in gastrocnemius muscle in the leg immobilization model, an activity significantly antagonized by bezafibrate administration in vivo. We conclude that bezafibrate could serve as a therapeutic agent for immobilization-induced muscle atrophy.

Comparison of Surgical Outcomes After Posterior Decompression by Junior or Senior Surgeons for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Results From Retrospective Multicenter Cohort Study.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate surgical outcomes following posterior decompression for cervical ossification of the posterior longitudinal ligament (OPLL) when performed by board-certified spine (BCS) or non-BCS (NBCS) surgeons. METHODS: We included 203 patients with cervical OPLL who were followed for a minimum of 1 year after surgery. Demographic information, medical history, and imaging findings were collected. Clinical outcomes were assessed preoperatively and at the final follow-up using the Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) for the neck. We compared outcomes between BCS surgeons, who must meet several requirements, including experience in more than 300 spinal surgeries, and NBCS surgeons. RESULTS: BCS surgeons performed 124 out of 203 cases, while NBCS surgeons were primary in 79 cases, with 73.4% were directly supervised by a BCS surgeon. There was no statistically significant difference in surgical duration, estimated blood loss, and perioperative complication rates between the BCS and NBCS groups. Moreover, no statistically significant group differences were observed in each position of the C2-7 angle and cervical range of motion at preoperation and the final follow-up. Preoperative and final follow-up JOA scores, VAS for the neck, and JOA score recovery rate were comparable between the two groups. CONCLUSIONS: Surgical outcomes, including functional recovery, complication rates, and cervical dynamics, were comparable between the BCS and NBCS groups. Consequently, posterior decompression for cervical OPLL is considered safe and effective when conducted by junior surgeons who have undergone training and supervision by experienced spine surgeons.

Development and Validation of Machine Learning-Based Predictive Model for Prolonged Hospital Stay after Decompression Surgery for Lumbar Spinal Canal Stenosis.

Introduction: Precise prediction of hospital stay duration is essential for maximizing resource utilization during surgery. Existing lumbar spinal stenosis (LSS) surgery prediction models lack accuracy and generalizability. Machine learning can improve accuracy by considering preoperative factors. This study aimed to develop and validate a machine learning-based model for estimating hospital stay duration following decompression surgery for LSS. Methods: Data from 848 patients who underwent decompression surgery for LSS at three hospitals were examined. Twelve prediction models, using 79 preoperative variables, were developed for postoperative hospital stay estimation. The top five models were chosen. Fourteen models predicted prolonged hospital stay (≥14 days), and the most accurate model was chosen. Models were validated using a randomly divided training sample (70%) and testing cohort (30%). Results: The top five models showed moderate linear correlations (0.576-0.624) between predicted and measured values in the testing sample. The ensemble of these models had moderate prediction accuracy for final length of stay (linear correlation 0.626, absolute mean error 2.26 days, standard deviation 3.45 days). The c5.0 decision tree model was the top predictor for prolonged hospital stay, with accuracies of 89.63% (training) and 87.2% (testing). Key predictors for longer stay included JOABPEQ social life domain, facility, history of vertebral fracture, diagnosis, and Visual Analogue Scale (VAS) of low back pain. Conclusions: A machine learning-based model was developed to predict postoperative hospital stay after LSS decompression surgery, using data from multiple hospital settings. Numerical prediction of length of stay was not very accurate, although favorable prediction of prolonged stay was accomplished using preoperative factors. The JOABPEQ social life domain score was the most important predictor.

Rupture of the Flexor Pollicis Longus Tendon Involved between the Radial Shaft and the Volar Locking Plate.

We report the case of a 61-year-old woman with right-sided flexor pollicis longus (FPL) tendon ruptured a month after volar locking plate fixation. Five months after the initial operation, hardware removal and reconstruction of the FPL tendon with the ipsilateral palmaris longus were performed. The proximal stump of the ruptured FPL tendon was found in the space between the distal radius and plate.

Impact of pleural effusion at an early period after posterior spinal fusion for adolescent idiopathic scoliosis on future pulmonary function and lung volume.

Background: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has a potential risk for postoperative pleural effusion. Although pleural effusion at an early period after PSF for AIS occurs with a relatively high frequency and occasionally requires some treatments, the impact of postoperative pleural effusion on future pulmonary function or lung volume (LV) has not been clarified to date. The aim of this study was to evaluate the effect of pleural effusion after PSF for AIS on the postoperative pulmonary function and LV. Methods: A total of 114 consecutive patients who underwent PSF for AIS followed up greater than 2 years at our institute were retrospectively reviewed. We evaluated postoperative pleural effusion by computed tomography (CT) at the 1-week follow-up and divided patients into the pleural effusion (PF) and non-pleural effusion (NP) groups. We investigated spirometry parameters recorded for testing included vital capacity (VC), forced expiratory volume in the first second (FEV1), %VC, and FEV1% and measured the LV using CT images and a workstation at baseline and 2 years after surgery. Results: A total of 87 (76.3%) patients with postoperative pleural effusion were identified, but all patients were asymptomatic and did not require additional treatment for postoperative pleural effusion. All pulmonary function parameters at the 2-year follow-up exhibited no significant differences between the two groups. Although preoperative left LV (1.21±0.30 L vs. 1.36±0.34 L; p=.022) and total LV (2.68±0.62 L vs. 2.99±0.73 L; p=.031) were significantly lower in the PF group than in the NP group, all postoperative LV parameters were similar between the two groups. Conclusions: Pleural effusion at an early period after PSF for AIS was a postoperative occurrence without an impact on future pulmonary function and LV.