Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report.

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

Risk Factors for Residual Back Pain After Balloon Kyphoplasty for Osteoporotic Vertebral Fracture.

Background: Balloon kyphoplasty (BKP) is a method for the management of osteoporotic vertebral body fracture (OVF). However, improvement in back pain (BP) is poor in some patients, also previous reports have not elucidated the exact incidence and risk factors for residual BP after BKP. We clarified the characteristics of residual BP after BKP in patients with OVF. Hypothesis: In this study, we hypothesize that some risk factors may exist for residual BP 2 years after the treatment of OVF with BKP. Patients and Methods: A multicenter cohort study was performed where patients who received BKP within 2 months of OVF injury were followed-up for 2 years. BP at 6 months after surgery and final observation was evaluated by Visual Analog Scale (VAS) score. Patients with a score of 40 mm or more were allocated to the residual BP group, and comparisons between the residual back pain group and the improved group were made for bone density, kyphosis, mobility of the fractured vertebral body, total spinal column alignment, and fracture type (fracture of the posterior element, pedicle fracture, presence or absence of posterior wall damage, etc.). Also, Short Form 36 (SF-36) for physical component summary (PCS) and mental component summary (MCS) at the final follow-up was evaluated in each radiological finding. Results: Of 116 cases, 79 (68%) were followed-up for 2 years. Two years after the BKP, 26 patients (33%) experienced residual BP. Neither age nor sex differed between the groups. In addition, there was no difference in bone mineral density, BKP intervention period (period from onset to BKP), and osteoporosis drug use. However, the preoperative height ratio of the vertebral body was significantly worse in the residual BP group (39.8% vs. 52.1%; p = 0.007). Two years after the operation, the vertebral body wedge angle was significantly greater in the residual BP group (15.7° vs. 11.9°; p = 0.042). In the multiple logistic regression model with a preoperative vertebral body height ratio of 50% or less [calculated by receiver operating characteristic (ROC) curve], the adjusted odds ratio for residual BP was 6.58 (95% confidence interval 1.64-26.30; p = 0.007); similarly, patients with vertebral body height ratio less than 50% had a lower score of SF-36 PCS 24.6 vs. 32.2 p = 0.08. Conclusion: The incidence of residual BP 2 years after BKP was 33% in the current study. The risk factor for residual BP after BKP was a preoperative vertebral body height ratio of 50% or less, which should be attentively assessed for the selection of a proper treatment scheme and to provide adequate stabilization. Level of Evidence: III.

Automatic Segmentation of Vestibular Schwannomas: A Systematic Review.

BACKGROUND: Vestibular Schwannomas (VS) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS. METHODS: Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and CATS, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized. RESULTS: Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions. CONCLUSION: Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust, well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability.

Time-to-onset Analysis of Rhabdomyolysis due to Different Proton Pump Inhibitors Using a Pharmacovigilance Database.

BACKGROUND/AIM: Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database. PATIENTS AND METHODS: Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined. RESULTS: RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan. CONCLUSION: The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.

Comparison of the physicochemical properties of branded and generic glucose-added maintenance hypotonic infusion fluids to assess the potential for phlebitis and incompatibility with other drugs.

In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids. We have previously reported that in other types of electrolyte infusion fluids, a variation in pH can cause incompatibility with other drugs, and variation in titratable acidity and osmolality can lead to phlebitis. Glucose-added maintenance hypotonic infusion fluid (listed as type-3G) is commonly used as a maintenance solution when energy support is needed. However, nonvolatile acid is added to prevent the caramelization of glucose, resulting in higher osmolality and titratable acidity and lower pH. Therefore, we hypothesized that both phlebitis and incompatibility with other drugs are likely to occur; hence, we measured and evaluated the physicochemical properties of branded and generic type-3G infusion fluids. We show that the osmolality, pH, and titratable acidity of all evaluated branded and generic products differed significantly and that these properties should be evaluated together to avoid phlebitis and incompatibility with other drugs when switching between branded and generic type-3G infusion fluids.

Differences in spine growth potential for Sanders maturation stages 7A and 7B have implications for treatment of idiopathic scoliosis.

PURPOSE: This study aimed to clarify the differences in spine and total body height growth and curve progression between Sanders maturation stage (SMS) 7A and 7B in patients with adolescent idiopathic scoliosis (AIS). METHODS: This retrospective case-control study involving patients with AIS at SMS 7 evaluated the differential gains in the spine (T1-S1) and total body height and curve progression between SMS 7A and 7B. A validated formula was used to calculate the corrected height, accounting for height loss due to scoliosis. A multivariable non-linear and logistic regression model was applied to assess the distinct growth and curve progression patterns between the SMS 7 subtypes, adjusting for potential confounders. RESULTS: A total of 231 AIS patients (83% girls, mean age 13.9 ± 1.2 years) were included, with follow-up averaging 3.0 years. Patients at SMS 7A exhibited larger gains in spine height (9.9 mm vs. 6.3 mm) and total body height (19.8 mm vs. 13.4 mm) compared with SMS 7B. These findings remained consistent even after adjustments for curve magnitude. Non-linear regression models showed continued spine and total body height increases plateauing after 2 years, significantly greater in SMS 7A. More SMS 7A patients had curve progression over 10°, with an adjusted odds ratio of 3.31. CONCLUSION: This study revealed that patients staged SMS 7A exhibited more spine and total body growth and a greater incidence of substantial curve progression than those at 7B. These findings imply that delaying brace discontinuation until reaching 7B could be beneficial, particularly for those with larger curves. LEVEL OF EVIDENCE: Level III (Case-control study).

Do Pedicle Screws That Terminate in the Costovertebral Joint Compromise Proximal Anchor Fixation in a Dual Growing Rod Construct?

INTRODUCTION: Growing rods (GRs) are used to treat early-onset scoliosis (EOS) recalcitrant to bracing and casting. Proximal anchor pullout, a known complication of GR constructs, can result in spinal cord injury if pedicle screw anchors are placed with a lateral-to-medial trajectory. To mitigate this risk, a more straightforward and potentially safer trajectory may result in screws that terminate within the costovertebral joint (CVJ). We asked, how often does CVJ placement occur and does this technique increase the rate of failure in GR constructs? METHODS: We retrospectively reviewed 35 patients with EOS treated with dual GR with >2-year follow-up excluding patients with skeletal dysplasia or history of previous posterior instrumentation. Patient demographics, radiographic parameters, and implant constructs were assessed. RESULTS: Of patients meeting the inclusion criteria, 18/35 (51%) were females with an average age of 7.96 (range: 4.0 to 15.2) years at surgery with a follow-up of 3.7 (range: 2.0 to 7.7) years. Five (14%) patients had idiopathic EOS, 5 (14%) had congenital EOS, 12 (34%) had neuromuscular EOS, 10 (29%) had syndromic scoliosis, and 3 (9%) had another etiology for EOS. Among 195 proximal pedicle screws placed, 19 (10%) terminated within the CVJ, and 13 patients (37%) had at least 1 CVJ screw. Two patients (6%) experienced unilateral proximal pullout. In both patients, the anchors on the affected side included 1 of 2 screws within the CVJ. Both patients had constructs that included 2 screws on the side that pulled out and 3 screws on the side that did not. None of the remaining 17 CVJ screws led to implant failure. CONCLUSION: Pedicle screw placement within the CVJ is common and does not appear to significantly contribute to proximal screw pullout; however, it may contribute to unilateral implant failure in constructs employing only 2 proximal screws, where 1 of those 2 screws terminates within the CVJ. Construct modifications should be considered in this scenario. LEVEL OF EVIDENCE: Level III.

Association of Torsade de Pointes and QT Prolongation With Antifungal Triazoles: Analysis Using a Pharmacovigilance Database.

BACKGROUND/AIM: Torsade de pointes (TdP)/QT prolongation (QTP) is one of the most life-threatening adverse effects of antifungal triazoles. The aim of the present study was to evaluate the association of antifungal triazoles with TdP/QTP by age group and the profile of the time of TdP/QTP onset by analyzing the spontaneous adverse event database for Japan. PATIENTS AND METHODS: Data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to March 2022 were analyzed. The association between the administration of antifungal triazoles and TdP/QTP according to age was evaluated using an adjusted reporting odds ratio (aROR). In addition, the time-to-onset of TdP/QTP after antifungal triazole treatment was analyzed using the Weibull distribution according to the route of administration. RESULTS: Antifungal triazole treatment was associated with TdP/QTP (aROR=1.77, 95% confidence interval=1.52-2.07). In the subgroup analyses by age group, antifungal triazole treatments in patients ≤29 years old and ≥50 (except ≥90) years old were associated with TdP/QTP. The medians (quartiles) of time-to-onset for intravenous and oral antifungal triazole treatment were 8 (6-12) and 23 (8-86) days, respectively. In addition, the shape parameter in the Weibull distribution analysis of oral triazole treatment revealed that the hazard exhibited an early failure profile. CONCLUSION: TdP/QTP is associated with antifungal triazoles even in young patients, and patients should be monitored for the development of TdP/QTP, especially early after the initiation of treatment.

Bone alterations of pamidronate therapy in children with cerebral palsy complicating orthopedic management.

Cerebral palsy (CP) is a heterogeneous group of disorders with different clinical types and underlying genetic variants. Children with CP are at risk for fragility fractures secondary to low bone mineral density, and although bisphosphonates are prescribed for the treatment of children with bone fragility, there is limited information on long-term bone impact and safety. Children with CP usually present overtubulated bones, and the thickening of cortical bone by pamidronate treatment can potentially further narrow the medullary canal. Our purpose was to report bone alterations attributable to pamidronate therapy that impact orthopedic care in children with CP. The study consisted of 41 children with CP treated with pamidronate for low bone mineral density from 2006 to 2020. Six children presented unique bone deformities and unusual radiologic features attributed to pamidronate treatment, which affected their orthopedic care. The cases included narrowing of the medullary canal and sclerotic bone, atypical femoral fracture, and heterotopic ossification. Treatment with bisphosphonate reduced the number of fractures from 101 in the pretreatment period to seven in the post-treatment period (P < 0.001). In conclusion, children with CP treated with bisphosphonate have a reduction in low-energy fractures; however, some fractures still happen, and pamidronate treatment can lead to bone alterations including medullary canal narrowing with sclerotic bone and atypical femoral fractures. In very young children, failure to remodel may lead to thin, large femoral shafts with cystic medullary canals. More widespread use of bisphosphonates in children with CP may make these bone alterations more frequent. Level of evidence: Level IV: Case series with post-test outcomes.

Subclassification of Sanders Maturation Stage 3 Demonstrates Differences in Spine and Total Height Velocity Between 3A and 3B in Patients with Idiopathic Scoliosis.

STUDY DESIGN: A single-center retrospective case-control study. OBJECTIVE: To compare the spine and total height velocity between Sanders maturation stage (SMS) 3A and 3B. SUMMARY OF BACKGROUND DATA: Identifying SMS 3 is critical for treating growing children because it represents the early phase of rapid adolescent growth. However, there is limited literature available that clearly describes the growth differences between 3A and 3B. METHODS: The current study included consecutive patients with idiopathic scoliosis staged SMS 3 from January 2012 to December 2021. T1-S1 spine height, total body height, and curve magnitude were measured at the initial and follow-up visits. In addition to the spine and total height velocity calculated per month, corrected height velocity was estimated for curve magnitude using a validated formula. Mann-Whitney U test was used to compare SMS 3A and 3B outcomes, followed by a multiple linear regression model to evaluate the association of the SMS subclassifications to growth velocity adjusted for confounding factors. RESULTS: A total of 204 patients (66% girls, mean age: 12.3±1.3 y) met the inclusion criteria. Patients staged SMS 3A had higher spine height velocity (mm/month) in both girls (2.3 vs. 1.5, P<0.001) and boys (2.6 vs. 1.7, P<0.001), as well as total height velocity (mm/month; (5.8 vs. 4.3, P<0.001 for girls; 6.6 vs. 4.5, P<0.001 for boys). Corrected velocity showed similar results with greater spine and total height velocity in SMS 3A. Multivariate analysis indicated a significant association of the SMS subclassification to the spine and total height velocity. The scoliosis curve progression was comparable between SMS 3A and 3B. CONCLUSION: SMS 3A and 3B had differential growth velocity in the spine and total body height. These results advocated the significance of SMS 3 subclassification for managing scoliosis treatment, including observation, bracing, and surgical interventions with fusion and growth modulation. LEVEL OF EVIDENCE: Level III (Case-control study).

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

Risk Factors for Poor Outcome after Palliative Surgery for Metastatic Spinal Tumors.

Palliative surgery is performed to improve the quality of life of patients with spinal metastases. However, it is sometimes difficult to achieve the expected results because the patient's condition, and risk factors related to poor outcomes have not been well elucidated. This study aimed to evaluate the functional outcomes and investigate the risk factors for poor outcomes after palliative surgery for spinal metastasis. We retrospectively reviewed the records of 117 consecutive patients who underwent palliative surgery for spinal metastases. Neurological and ambulatory statuses were evaluated pre- and post-operatively. Poor outcomes were defined as no improvement or deterioration in functional status or early mortality, and the related risk factors were analyzed using multivariate logistic regression analysis. The results showed neurological improvement in 48% and ambulatory improvement in 70% of the patients with preoperative impairment, whereas 18% of the patients showed poor outcomes. In the multivariate analysis, low hemoglobin levels and low revised Tokuhashi scores were identified as risk factors for poor outcomes. The present results suggest that anemia and low revised Tokuhashi scores are related not only to life expectancy but also to functional recovery after surgery. Treatment options should be carefully selected for the patients with these factors.

Adjuvant Stereotactic Radiosurgery With or Without Postresection Fractionated Radiation Therapy for the Management of Clival Chordomas in Adults: An International Multicenter Case Series.

BACKGROUND: Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects. OBJECTIVE: To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group). METHODS: We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT). RESULTS: Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died ( P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group ( P = .04). CONCLUSION: Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas.

Physicochemical Properties of Branded and Generic Infusion Fluid Preparations: Results of a Comparative Experimental Study on Type 2 Hypotonic Infusion Fluid.

In Japan, four different types of hypotonic infusion fluids, namely, types 1-4, are available and used depending on the patient's condition. Although branded and generic products for each type of hypotonic infusion fluid are available, their physicochemical properties are unknown. For types 1 and 3 fluids, differences in the physicochemical properties of branded and generic products lead to different adverse events when administered. In the present study, we measured titration acidity, pH, and osmolality of branded and generic type 2 hypotonic infusion fluids, which have recently been recognized as useful for maintenance infusion among pediatric patients. We herein assessed their physicochemical information required while selecting a product in clinical practice. Experiments were performed using one branded and two generic products of type 2 hypotonic infusion fluids. Titration acidity was measured via neutralization titration, osmolality was measured via freezing point depression, and pH was measured via potentiometry using a glass electrode. Significant differences in titration acidity, which is a risk factor for metabolic acidosis, and pH, which is a risk factor for pH-dependent changes upon mixing, were observed between the branded and generic products. Our study indicates that titration acidity and pH should be evaluated appropriately to avoid adverse events in clinical practice while selecting a product of type 2 hypotonic infusion fluids. Our findings highlight the importance of evaluating the differences between branded and generic products, specifically when selecting it for pediatric patients with incompletely developed renal function and patients with impaired renal function.

Pneumothorax by Penetrating Endplate Screw for Diffuse Idiopathic Skeletal Hyperostosis-Related Thoracolumbar Fracture.

Pneumothorax is a rare surgical complication in spinal surgery with thoracic pedicle screws. The penetrating endplate screw (PES) technique has been developed as a strong alternative spinal anchor to conventional pedicle screws for diffuse idiopathic skeletal hyperostosis (DISH). We present an intraoperative pneumothorax without deviation to the thoracic during the maneuver of the PES. A 56-year-old male who presented with non-union of DISH-related T12 vertebral fracture underwent T12 kyphoplasty and T10-L2 posterior fixation using the PES technique. The left pneumothorax was developed postoperatively without screw deviation to the thorax throughout screw insertion. Postoperative CT suggested that a displaced rib head by the lateral misposition of the screw at the inserting point and the pedicle level might injure the pleura. Spine surgeons should know that the lateral insertion of PES has a potential risk for pneumothorax by the displacement of the rib head because of screw trajectory from caudal to cranial apart from conventional pedicle screw.

Relationship between body mass index and spinal pathology in community-dwelling older adults.

PURPOSE: To clarify the relationship between body mass index (BMI) and spinal pathologies including spinal sagittal balance, back extensor strength (BES), paraspinal muscle mass, prevalent vertebral fracture, disc degeneration, Modic changes, low back pain, and quality of life (QOL) in community-dwelling older adults. METHODS: This study included 380 participants (age: ≥ 65 years, male/female: 152/228) from the Shiraniwa Study. Multivariate nonlinear regression analysis was used to investigate the relationship between BMI and sagittal vertical axis (SVA), BES, paraspinal muscle mass, visual analog scale (VAS) for low back pain, Oswestry Disability Index (ODI), and EuroQoL-5 Dimension (EQ5D) score after adjusting for sex, age, Hospital Anxiety and Depression Scale score, and Charlson Comorbidity Index. In addition, multiple logistic regression analysis was used to investigate the association between BMI and prevalent vertebral fracture, disc degeneration, and Modic changes. RESULTS: BMI was significantly correlated with SVA, BES, paraspinal muscle mass, VAS, ODI, and EQ5D score. The increase in BMI was associated with the deterioration of all outcomes, which accelerated when the BMI increased from approximately 22-23 kg/m2. Moreover, overweight/obesity was significantly correlated with disc degeneration and Modic changes. CONCLUSION: Increased BMI is significantly associated with spinal pathologies such as SVA, BES, paraspinal muscle mass, VAS, QOL, disc degeneration, and Modic changes. The findings suggest that measures for controlling overweight and obesity among older adults can play an important role in the prevention and treatment of spinal pathologies.

Inverse association between DPP-4 inhibitor use and fracture in older adults: A disproportionality analysis of the FAERS and JADER.

OBJECTIVE: Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan. MATERIALS AND METHODS: Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis. RESULTS: Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73 - 0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59 - 0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68 - 0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52 - 0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35 - 0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data. CONCLUSION: Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Development of locomotive syndrome in elderly population after COVID-19 outbreak: A population-based cross-sectional study with over 12,000 participants.

BACKGROUND: Restrictions during the coronavirus disease 2019 (COVID-19) pandemic have decreased physical activity levels, which may result in locomotive syndrome. This study evaluated the change in locomotive syndrome prevalence and associated risk factors among an elderly population before and after a coronavirus outbreak. METHODS: This written self-administered cross-sectional survey was conducted in conjunction with the coronavirus disease vaccination program in Habikino City, Japan. Participants who were aged ≥65 years completed the five-question Geriatric Locomotive Function Scale before and during the pandemic. The diagnosis of locomotive syndrome and its stage was based on the Geriatric Locomotive Function Scale score: stage 1 (2-3 points), 2 (4-5 points), and 3 (≥6 points). Data on lifestyle changes, including regular exercise, during the pandemic were collected. RESULTS: This study included 12,197 participants (36.7% of the city's total elderly residents). The prevalence of locomotive syndrome increased from 41.3% to 47.1% after the outbreak. In total, 765 (6.3% of overall population) and 295 (9.5% of the participants who had stages 1-2 before the pandemic) participants developed locomotive syndrome and stage 3 locomotive syndrome, respectively. The multivariate logistic regression analysis indicated that a decrease in exercise was significantly associated with the onset of locomotive syndrome (all stages) (odds ratio = 2.5, p < 0.001) and locomotive syndrome stage 3 (odds ratio = 2.6, p < 0.001). CONCLUSIONS: Extrapolation of the study's findings to the entire population of Japan suggests that approximately 2 million elderly individuals might develop locomotive syndrome after the coronavirus outbreak. Additionally, 10% of the participants with mild-moderate locomotive syndrome before the pandemic may develop severe locomotive syndrome after the outbreak. The greatest risk factor for new-onset or worsening locomotive syndrome was a decrease in daily exercise. Thus, there is an urgent need for adequate exercise guidelines during the coronavirus pandemic, especially for the elderly population.