Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

Effects of bisphosphonates and treadmill exercise on bone and kidney in adenine-induced chronic kidney disease rats.

INTRODUCTION: The increasing prevalence of osteoporosis and chronic kidney disease (CKD) due to the aging of society has highlighted the need for development of effective treatments for elderly patients. This study examined whether the combination of treadmill exercise therapy and alendronate (ALN) can improve bone mineral density (BMD) and bone strength without worsening renal function in adenine-induced CKD model rats. MATERIALS AND METHODS: 8-week-old male Wistar rats (n = 70) were divided into experimental groups based on the treatment protocol, i.e., non-CKD (control), vehicle only (CKD), ALN only, exercise only, and combined ALN plus exercise. A 0.75% adenine diet was used to induce CKD. Groups were killed at either 20 or 30 weeks of age. Comprehensive assessments included serum and urine biochemistry tests, renal histology, bone histomorphometry, BMD measurement, micro-computed tomography examinations, and biomechanical testing. RESULTS: Blood biochemistry tests, urine analyses and histological evaluations of the kidney demonstrated that ALN treatment did not worsen renal function or kidney fibrosis in moderate-stage CKD model rats. Both ALN and treadmill exercise significantly suppressed bone resorption (p < 0.05-p < 0.01). Moreover, ALN monotherapy and combined ALN and treadmill exercise significantly improved BMD of the lumbar spine and femur, bone microstructure, and trabecular bone strength (p < 0.05-p < 0.01). Treadmill exercise was also shown to decrease cortical porosity at the mid-diaphysis of the femur and improve kidney fibrosis. CONCLUSION: The combination of ALN and treadmill exercise is effective in improving BMD, the microstructure of trabecular and cortical bone, and bone strength, without compromising renal function in adenine-induced CKD model rats.

Effects of electroconvulsive therapy on the use of anxiolytics and sleep medications: a propensity score-matched analysis.

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.

Drug-induced liver injury associated with high-dose ceftriaxone: a retrospective cohort study adjusted for the propensity score.

PURPOSE: Ceftriaxone has been recognized as a well-tolerated drug; however, in some instances, liver dysfunction occurs after using high-dose ceftriaxone. We aimed to assess the incidence of liver injury due to high-dose ceftriaxone and to determine whether there is a dose-dependent risk of liver injury with this drug. METHODS: We conducted a retrospective cohort study of hospitalized adult patients treated with ceftriaxone at a tertiary care hospital from January 2012 to October 2013. We collected demographic and clinical data by reviewing their medical records. The incidence of liver injury based on biochemical criteria, defined as a primary outcome, was compared between patients treated with high-dose ceftriaxone (4 g/day) and those treated with a normal dose of ceftriaxone (2 g/day) for ≥5 consecutive days. A propensity score for the use of high-dose ceftriaxone was calculated from five factors. RESULTS: We identified 37 patients treated with high-dose ceftriaxone and 434 patients treated with a normal dose of ceftriaxone. Among these 471 patients, 15 patients (3.2 %) experienced liver injury, of whom six patients (6/37, 16.2 %) had received high-dose ceftriaxone and nine patients (9/434, 2.1 %) had received normal doses of ceftriaxone. In the multivariate analysis adjusted for the propensity score, high-dose ceftriaxone was independently associated with liver injury (odds ratio, 7.23; 95 % confidence interval, 2.01-26.0). CONCLUSIONS: The present study revealed that high-dose ceftriaxone was associated with a significantly higher incidence of liver injury compared with the normal-dose regimen. Therefore, clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use.

Pediatric femoral shaft fracture requiring revision surgery for nonunion associated with vitamin D and K deficiencies: a case report.

BACKGROUND: Nonunion of femoral shaft fractures in children is rare, and there is no clear treatment protocol. In this case report, a pediatric femoral shaft fracture that developed in nonunion due to vitamin deficiency after osteosynthesis, which was successfully treated with vitamin augmentation and replacement with a rigid antegrade intramedullary nail, is described. CASE PRESENTATION: The patient is an 11-year-old Japanese girl. She injured her right femoral shaft fracture when she hit a wall after kickboarding down a hill and underwent osteosynthesis with a titanium elastic nail. Six months postoperatively, she developed nonunion, was found to be deficient in vitamins D and K, and was started on vitamin supplementation. She underwent replacement with a rigid antegrade intramedullary nail at 7 months postoperatively, and bone union was achieved 3 months after reoperation. CONCLUSION: When delayed union of a fracture is observed postoperatively, even in children without underlying disease, the cause of the problem must be investigated and treated promptly.

Teriparatide and etelcalcetide improve bone, fibrosis, and fat parameters in chronic kidney disease model rats.

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (N = 9-10 in each group): CKD group (vehicle administration), TPTD group (30 µg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions: With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

Characteristics and Treatment Strategies for Basicervical and Transcervical Shear Fractures of the Femoral Neck.

This study aimed to define basicervical and transcervical shear fractures using area classification and to determine the optimal osteosynthesis implants for them. The clinical outcomes of 1042 proximal femur fractures were investigated. A model of the proximal femur of a healthy adult was created from computed tomography images, and basicervical and transcervical shear fractures were established in the model. Osteosynthesis models were created using a short femoral nail with a single lag screw or two lag screws and a long femoral nail with a single lag screw or two lag screws. The minimum principal strains of the fracture surfaces were compared when the maximum loads during walking were applied to these models using finite element analysis software. Basicervical fractures accounted for 0.96% of all proximal femur fractures, 67% of which were treated with osteosynthesis; the failure rate was 0%. Transcervical shear fractures accounted for 9.6% of all proximal femur fractures, 24% of which were treated with osteosynthesis; the failure rate was 13%. Finite element analysis showed that transcervical shear fracture has high instability. To perform osteosynthesis, multiple screw insertions into the femoral head and careful postoperative management are required; joint replacement should be considered to achieve early mobility.

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

BACKGROUND/AIM: This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma. MATERIALS AND METHODS: CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed. RESULTS: Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS. CONCLUSION: The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

Distal sacral nerve roots severed by a fragility fracture of the sacrum: a case report.

BACKGROUND: Owing to the aging population, fragility fractures of the pelvis are occurring more frequently. Fixation of the fracture and stabilization of the pelvic ring usually provide good clinical results. A case of distal sacral nerve roots severed by a fragility fracture of the sacrum is presented. CASE PRESENTATION: A 62-year-old Japanese woman with schizophrenia with low back pain, gait disorder, dysuria, and fecal incontinence presented to an emergency department, and plain X-rays showed no findings. She also complained of dysuria, and neurogenic bladder and cystitis were diagnosed. One month later, she was admitted to a psychiatric hospital for exacerbation of schizophrenia. In hospital, she had a urethral catheter inserted and spent 3 months in bed. She was referred to our orthopedic department because a gait disorder was discovered after her mental condition improved and she was permitted to walk. On examination, she could not walk and had decreased sensation from the buttocks to both posterior thighs and around the anus and perineum. Manual muscle testing of her lower limbs showed mild weakness of about 4 in bilateral flexor hallucis longus and gastrocnemius, and bilateral Achilles tendon reflexes were lost. Her anal sphincter did not contract, and urinary retention continued after urethral catheter removal. Imaging examinations showed an H-shaped sacral fracture consisting of a transverse fracture with displacement of the third sacral vertebra and vertical fractures of the bilateral sacral wings, with severe stenosis of the spinal canal at the site of the transverse fracture. The patient was diagnosed as having bladder and rectal dysfunction due to a displaced, unstable sacral fracture. First to third sacral laminectomy and alar-iliac fixation using percutaneous pedicle screws and sacral alar-iliac screws were then performed. The bilateral distal sacral nerve roots (S3, S4, S5) were completely severed at the second to third sacral levels, but bilateral second sacral nerve roots were not compressed from the bifurcation to the sacral foramen. Postoperatively, bladder and rectal dysfunction remained, but the low back pain was alleviated. Two weeks postoperatively, she could walk with a walker and was discharged. Three months after the operation, bone fusion of the fracture was observed. CONCLUSIONS: In cases of bladder-rectal dysfunction with low back pain, the possibility of sacral fracture should be considered, and computed tomography, magnetic resonance imaging, and X-ray examinations should be performed. Even sacral fractures without displacement require attention because they can cause serious injury in the event of a nerve root being severed if not diagnosed early and given appropriate treatment.

Intravascular Administration of Acridine Orange and Zoledronate in a Bone Metastasis Model of Breast Cancer.

BACKGROUND/AIM: This study evaluated the effect of haematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases. MATERIALS AND METHODS: E0771 cells (1.0×105 cells/10 µl) were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment (drugs and irradiation) and were reared and sacrificed after 6 weeks. Micro-computed tomography (µCT) was performed to calculate the destruction rate of the femur bone. We measured tumour weight and volume at sacrifice and performed terminal deoxynucleotidyl transferase dUTP Nick-End Labelling staining of tumours. RESULTS: At 4 weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At 6 weeks, the AO+ZOL group had a lower bone destruction rate than the control and radiation groups; the ZOL group had a lower rate than the radiation group. The AO and AO+ZOL groups had suppressed tumour weight and volume compared to the control and radiation groups. The number of extraosseous apoptotic cells was higher in the AO+ZOL group than in all other groups except the AO group. CONCLUSION: In a model of local bone metastasis of breast cancer, haematogenous administration of AO reduced tumour size and more so when combined with ZOL.

Effective Treatment for Breakage of a Solid Long Cementless Stem with a Distal Locking Screw: A Case Report.

Introduction: Fractures around the femoral stem are difficult complications to treat. In revision surgery, good results can be obtained by a long cementless stem with a distal locking screw. However, there are few reports of treatment for cases where the stem itself is broken. Case Report: The case of a 69-year-old woman in which the femoral stem that was broken 5 years after performing revision surgery for a right periprosthetic femoral fracture was repaired using a solid long stem with a distal locking screw is presented. Her past history included osteoporosis and rheumatoid arthritis. She fell due to sudden right thigh pain and was then taken to the emergency department of our hospital. X-ray examination showed breakage of the stem itself at the position of the distal locking screw hole closest to the previous fracture. Revision total hip arthroplasty using a larger diameter stem of the same model was performed. The previous fracture site had been a fibrous non-union, and the femur proximal to the previous fracture site had severe atrophy and bone loss due to stress shielding. Two years after surgery, the patient can walk without pain, and progression of stress shielding, loosening of the stem, and breakage of the implants have not occurred. Conclusion: In the present case, non-union, proximal bone atrophy, the location of the hole of the distal locking screw, and insufficient stem strength were the causes of stem breakage. It is necessary to take measures such as bone grafting and select a stem as long as possible for the position of the distal locking screw to be as far as possible from the fracture line when using a narrow long stem with a distal locking screw.