Do standardization of the procedure reduce measurement variability of the sonographic anterior drawer test of the ankle?

BACKGROUND: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change. METHODS: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively. RESULTS: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group. CONCLUSION: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided.

Reliability and validity of the Forgotten Joint Score-12 for total ankle replacement and ankle arthrodesis.

OBJECTIVES: This study evaluated the reliability and validity of the Forgotten Joint Score-12 (FJS-12)-a measure of patients' ability to forget their joints in daily life-in patients who underwent total ankle replacement (TAR) or ankle arthrodesis (AA). METHODS: Patients who underwent TAR or AA were recruited from seven hospitals. The patients completed the Japanese version of FJS-12 twice, at an interval of two weeks, at a minimum of one year postoperatively. Additionally, they answered the Self-Administered Foot Evaluation Questionnaire and EuroQoL 5-Dimension 5-Level as comparators. The construct validity, internal consistency, test-retest reliability, measurement error, and floor and ceiling effects were evaluated. RESULTS: A total of 115 patients (median age, 72 years), comprising 50 and 65 patients in the TAR and AA groups respectively, were evaluated. The mean FJS-12 scores were 65 and 58 for the TAR and AA groups, respectively, with no significant difference between groups (P = 0.20). Correlations between the FJS-12 and Self-Administered Foot Evaluation Questionnaire subscale scores were good to moderate. The correlation coefficient ranged from 0.39 to 0.71 and 0.55 to 0.79 in the TAR and AA groups, respectively. The correlation between the FJS-12 and EuroQoL 5-Dimension 5-Level scores was poor in both groups. The internal consistency was adequate, with Cronbach's α greater than 0.9 in both groups. The intraclass correlation coefficients of test-retest reliability was 0.77 and 0.98 in the TAR and AA groups, respectively. The 95% minimal detectable change values were 18.0 and 7.2 points in the TAR and AA groups, respectively. No floor or ceiling effect was observed in either group. CONCLUSIONS: The Japanese version of FJS-12 is a valid and reliable questionnaire for measuring joint awareness in patients with TAR or AA. The FJS-12 can be a useful tool for the postoperative assessment of patients with end-stage ankle arthritis.

Association of Preoperative Depression Score With Outcomes of Transfibular Total Ankle Arthroplasty.

Favorable short-term results of transfibular total ankle arthroplasty have been reported in several studies; however, the factors affecting these results have not been elucidated. This study aimed to determine whether preoperative depression affects the outcome of transfibular total ankle arthroplasty and whether depression changes with surgery. Scores from the Japanese Society of Surgery of the Foot Ankle/Hindfoot scale (JSSF scale), Self-Administered Foot Evaluation Questionnaire (SAFE-Q), Hospital Anxiety and Depression Scale (HADS), and Timed Up & Go test (TUG) were collected preoperatively, at 6 months, and at 1 year postoperatively from 20 patients. Eighteen patients were diagnosed with osteoarthritis and 2 patients with rheumatoid arthritis. The mean age of the patients was 75 years. Patients were divided into 2 groups: those with preoperative HADS depression scores above the median (higher depression score group) and below the median (lower depression score group), and intergroup comparisons were made. No significant differences were observed in the JSSF and TUG scores between the groups, both preoperatively and postoperatively. Meanwhile, the SAFE-Q pain subscale score was significantly lower in the higher depression score group than in the lower depression score group (median, 59 vs 90) 1 year postoperatively. There were no differences in the other SAFE-Q subscale scores between the groups. The results suggested that depressive tendencies did not affect postoperative functional results using objective assessment measures but had a negative impact on pain in subjective assessment measures.

Impact of pain in other body regions on the foot-specific quality of life in patients with hallux valgus.

OBJECTIVES: The purpose of this study was to clarify the prevalence of pain outside the foot, and to determine the associations of pain outside the foot with foot-specific quality of life (QOL) in patients with hallux valgus. METHODS: Patients scheduled to undergo hallux valgus surgery were recruited. Patients answered whether they experienced disabling pain in 13 body regions other than the foot. Foot-specific QOLwas assessed using the Self-Administered Foot Evaluation questionnaire (SAFE-Q). Foot pain was quantified using the visual analogue scale (VAS). Patient characteristics, including age, sex, comorbidity, anxiety, and depression, were also surveyed. The association between pain elsewhere and the SAFE-Q and pain VAS scores were assessed using univariate and multivariate analyses. RESULTS: Of 102 patients, 55 (54%) experienced pain other than the foot. All SAFE-Q subscale scores were lower, and pain VAS was higher in patients with pain elsewhere than in patients without. In the multivariate analysis, an increase in the number of pain regions was independently associated with a decrease in SAFE-Q scores and an increase in pain VAS. CONCLUSION: More than half of the patients with hallux valgus experienced pain elsewhere. The presence of pain elsewhere was associated with poorer foot-specific QOL and severer foot pain.

Two cases of cervical esophageal perforation treated by surgery.

Cervical esophageal perforation is rare, but it is associated with high mortality. We describe two patients with cervical esophageal perforation that required surgical treatment. In both cases, good outcomes were evenly achieved, despite the presence of risk factors. A prompt diagnosis and treatment with collaboration between a surgeon and a gastroenterologist are important.

Pseudoaneurysm of the Peroneal Artery After Ankle Arthrodesis Treated by Endovascular Coil Embolization: A Case Report.

CASE: Pseudoaneurysms of the peroneal artery around the ankle joint have rarely been reported. We present the case of a 64-year-old man with a pseudoaneurysm of the anterior perforating branch of the peroneal artery associated with a screw inserted from the anterolateral distal tibia during ankle arthrodesis. Endovascular treatment with selective catheterization and coil embolization was successfully performed. The ankle joint achieved bone union without delay, and the pseudoaneurysm did not recur at the 18-month follow-up. CONCLUSION: This is the first report describing a pseudoaneurysm of the peroneal artery after ankle arthrodesis. Successful outcomes can be achieved by endovascular treatment.

Case ReportSubtrochanteric Fracture after Internal Fixation of Femoral Neck Fracture Using the Hansson Pinloc System: A Case Report.

Introduction: Hansson Pinloc system consists of three pins locking into a plate. In biomechanical trials, the novel plate design with its pin configuration enhanced torsional stability. Hansson Pinloc has been used for femoral neck fracture in some countries including Sweden and Japan. Recently, the outcome of a randomized clinical study comparing Hansson Pinloc and conventional Hansson pins was published. However, subtrochanteric fracture after internal fixation using Hansson Pinloc has not been reported in the English literature including the above report. Only several Japanese literatures reported some cases with this post-operative complication. We present a case with subtrochanteric fracture after internal fixation using Hansson Pinloc. Case Report: Subtrochanteric fractures after internal fixation of femoral neck fractures are rare but severe complications. We present our experience of this complication after internal fixation using Hansson Pinloc system which is a new design implant for femoral neck fracture. A 67-year-old woman was diagnosed with a femoral neck fracture of Garden stage I after a fall. She underwent closed reduction and internal fixation using Hansson Pinloc system. At 4 weeks after surgery, she suffered subtrochanteric fracture without any episode of trauma. The patient underwent removal of the instrumentation and internal fixation with a long femoral nail. We get in trouble with removing Hansson Pinloc system due to secondary fracture, and of bone defect. 9 weeks after the second surgery, the patient could get bone union and walk using double T-canes. Conclusion: Surgeons should be cognizant of this post-operative complication before using this system. In osteosynthesis of the femoral neck fracture using Hansson Pinloc, we should keep in mind that subtrochanteric fracture is a possible post-operative complication.

Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration.

Spiral ganglion neurons (SGNs) are primary auditory neurons in the spiral ganglion that transmit sound information from the inner ear to the brain and play an important role in hearing. Impairment of SGNs causes sensorineural hearing loss (SNHL), and it has been thought until now that SGNs cannot be regenerated once lost. Furthermore, no fundamental therapeutic strategy for SNHL has been established other than inserting devices such as hearing aids and cochlear implants. Here we show that the mouse spiral ganglion contains cells that are able to proliferate and indeed differentiate into neurons in response to injury. We suggest that SRY-box transcription factor 2/SRY-box transcription factor 10-double-positive (Sox2/Sox10-double-positive) Schwann cells sequentially started to proliferate, lost Sox10 expression, and became neurons, although the number of new neurons generated spontaneously was very small. To increase the abundance of new neurons, we treated mice with 2 growth factors in combination with valproic acid, which is known to promote neuronal differentiation and survival. This treatment resulted in a dramatic increase in the number of SGNs, accompanied by a partial recovery of the hearing loss induced by injury. Taken together, our findings offer a step toward developing strategies for treatment of SNHL.

Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury.

Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, we here examined combinatorial treatment of anti-HMGB1 mAb and epothilone B (Epo B), which has been reported to promote axon regeneration. This combinatorial treatment significantly increased hindlimb movement compared with anti-HMGB1 mAb alone, although Epo B alone failed to increase functional recovery. These results are in agreement with that anti-HMGB1 mAb alone was able to decrease the lesion area spreading and increase the surviving neuron numbers around the lesion, whereas Epo B facilitated axon outgrowth only in combination with anti-HMGB1 mAb, suggesting that anti-HMGB1 mAb-dependent tissue preservation is necessary for Epo B to exhibit its therapeutic effect. Taken together, the combinatorial treatment can be considered as a novel and clinically applicable strategy for SCI.

Surgical Treatment of Pathological Tibial Shaft Fracture in Adult Patient With Gnathodiaphyseal Dysplasia: A Case Report.

CASE: Gnathodiaphyseal dysplasia is a generalized skeletal syndrome characterized by frequent bone fractures in childhood, sclerosis and bowing of tubular bones, and cemento-osseous lesions of the jawbones. We present the case of a 53-year-old man with gnathodiaphyseal dysplasia who presented with pathological fracture of the tibial shaft. Internal fixation with the Ender nail was successfully performed with 2 years of follow-up. CONCLUSION: This is the first report describing the treatment of fracture in an adult patient with gnathodiaphyseal dysplasia. Internal fixation with the Ender nail was effective for the tubular bone with deformity. Callus formation was observed without delay.

Disease activity affects the recurrent deformities of the lesser toes after resection arthroplasty for rheumatoid forefoot deformity.

OBJECTIVES: The purpose of this study was to clarify the effect of disease activity on recurrent deformities after resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis (RA). METHODS: This study included 83 feet in 58 patients with RA who underwent resection arthroplasty of all metatarsal heads, with a minimum follow-up of 2 years. The patients' demographic characteristics, preoperative radiographic findings, and RA disease activity evaluated using the 28-joint disease activity score based on the erythrocyte sedimentation rate (determined preoperatively and at the final follow-up) were compared between feet with and without postoperative recurrent deformities of the toes. Recurrent deformities were assessed separately for the hallux and lesser toes. RESULTS: Recurrence in the hallux and lesser toes occurred in 23 feet (27.7%) and 13 feet (15.7%), respectively. With respect to recurrent hallux deformity, only the preoperative severity of hallux deformity was associated with recurrence. On the other hand, postoperative deformity of the lesser toes was positively associated with disease activity alone and not with other preoperative factors. CONCLUSION: Postoperative control of RA disease activity was associated with recurrent deformity of the lesser toes but not that of the hallux after resection arthroplasty of all metatarsals for rheumatoid forefoot deformities.

Evaluations of daily teriparatide using finite-element analysis over 12 months in rheumatoid arthritis patients.

INTRODUCTION: The objective of this study was to quantitatively evaluate the effects of daily teriparatide on rheumatoid arthritis patients using predicted bone strength (PBS) assessed by quantitative computed tomography-based finite-element analysis (QCT/FEA) and using bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), and to prospectively investigate clinical determinants associated with PBS and BMD increases. MATERIALS AND METHODS: Participants comprised 39 patients (mean age, 69 years; disease activity score assessing 28 joints with CRP, 3.0; previous vertebral fractures, 82%) enrolled in this study. BMD by DXA and PBS by QCT/FEA of lumbar spine (LS) and proximal femur were measured at baseline, and after 6 and 12 months. In the groups showing increases in these values, variables that may have affected these increases were evaluated using univariate logistic regression analysis. RESULTS: Daily teriparatide treatment significantly increased not only LS BMD, but also LS PBS in RA patients with osteoporosis after both 6 and 12 months of treatment. Increases in N-terminal type I procollagen propeptide (PINP) at 1 and 3 months were significantly associated with increased LS PBS at 12 months according to univariate logistic regression analysis. The threshold value for increased PINP at 1 month for increased PBS at 12 months was 75 µg/L. CONCLUSIONS: Increased LS PBS at 12 months was predicted by increased PINP at 1 month from baseline.

Time Course of Quality of Life Improvement Between Resection Arthroplasty and Metatarsophalangeal Joint-Preserving Forefoot Arthroplasty for Rheumatoid Arthritis.

BACKGROUND: Resection arthroplasty has long been a major treatment option for forefoot deformity caused by rheumatoid arthritis (RA). However, metatarsophalangeal (MTP) joint-preserving surgery is now surpassing classic resection arthroplasty. This study was performed to compare the postoperative results of these 2 operative methods. METHODS: Fifty-one toes of 40 patients with RA who underwent resection arthroplasty (resection group) or MTP joint-preserving arthroplasty (preservation group) from 2014 to 2017 for forefoot deformity were followed up for >1 year and were retrospectively analyzed. In the preservation group, open reduction of joint dislocation was performed if needed, and the deformity was corrected by metatarsal shortening osteotomy. The mean follow-up period was 21 months. The Japanese Society for Surgery of the Foot (JSSF) scales (objective outcome measures), the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) (subjective outcome measure), and radiographic indices were compared between the groups. The resection group and preservation group comprised 15 toes of 11 patients and 36 toes of 29 patients, respectively. RESULTS: There were no significant differences in the preoperative radiographic indices, JSSF scales, or SAFE-Q results between the 2 groups. The preservation group showed better JSSF scores at the last follow-up (median hallux scale, 89 vs 74; median lesser scale, 87 vs 79). In the preservation group, the SAFE-Q scores gradually improved with time until 12 months postoperatively. In the resection group, the scores decreased 3 months postoperatively and then improved and reached a plateau 6 months postoperatively. At 12 months postoperatively, there was no significant difference in the SAFE-Q scores between the 2 groups. CONCLUSIONS: MTP joint-preserving arthroplasty resulted in superior objective scores to resection arthroplasty in patients with RA forefoot deformity. Although the subjective scores did not differ between the groups at the last follow-up, the time course of postoperative quality of life improvement was different between the 2 surgeries. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Surgical Treatment for Toe Deformities in Stiff-Person Syndrome: A Case Report.

CASE: Stiff-person syndrome is a rare neurological disorder characterized by rigidity and painful spasms of the trunk and limbs, and patients sometimes have difficulty in walking due to rigid toe deformities. This is a case report of a 76-year-old woman suffering from stiff-person syndrome with painful rigid toe deformities regained walking ability after metatarsal osteotomy and cutting of the toe extensors for all toes in the left foot. CONCLUSION: For patients with stiff-person syndrome, surgical intervention is a powerful treatment option when they have developed rigid and painful toe deformities despite adequate pharmacological treatment.

Diagnosis of avulsion fractures of the distal fibula after lateral ankle sprain in children: a diagnostic accuracy study comparing ultrasonography with radiography.

BACKGROUND: The purpose of this study was to determine the diagnostic accuracy of ultrasonography for the diagnosis of avulsion fractures of the distal fibula for lateral ankle sprain in children and compare it to that of radiography. METHODS: Children who sustained lateral ankle sprain were prospectively surveyed. They underwent both ultrasonography and radiography at the first clinic visit to diagnose any concomitant avulsion fractures of the distal fibula. The patients underwent follow-up radiography 4 weeks later to obtain the reference standard diagnosis. The measures of diagnostic accuracy (i.e., sensitivity, specificity, positive predictive value, and negative predictive value) of the initial ultrasonography and radiography were calculated; they were then compared using the McNemar test. Totally, 52 patients (with a median age of 9 years) were analyzed. RESULTS: On the reference standard (follow-up) radiographs, 32 patients (62%) were found to have avulsion fractures of the distal fibula. The sensitivity, specificity, positive predictive value, and negative predictive value for ultrasonography were 94, 85, 91, and 89% respectively; and 81, 100, 100, and 77% respectively for radiography at the first visit. There were no significant differences in sensitivity and specificity between the two diagnostic methods (P = 0.22, 0.25). CONCLUSIONS: Ultrasonography has a high diagnostic accuracy, which is comparable to that of radiography, for the diagnosis of avulsion fracture of the distal fibula. Ultrasonography may be used as an option of imaging modality for lateral ankle sprain in children.

Synovial Metallosis After Ceramic Total Ankle Arthroplasty Treated With a Total Talar Prosthesis: A Case Report.

Total ankle arthroplasty is a useful surgical procedure for osteoarthritis of the ankle, but aseptic loosening of components is an issue. We report here a case of aseptic implant loosening with metallosis after total ankle arthroplasty using the TNK ankle (Kyocera, Kyoto, Japan), which occurred despite the components being ceramic. We also report favorable results from our method of treatment using a total talar prosthesis in the revision surgery. During the revision surgery, synovial metallosis was found, probably related to superficial damage to the screw affixing the tibial component to the bone. Because both the tibial and talar components were loose, all the components and the remaining talar bone were removed. A new tibial component and a custom-made alumina-ceramic total talar prosthesis was inserted. Pain relief was achieved and maintained through the latest follow-up visit at 42 months after revision surgery. Dorsiflexion of the ankle improved from 0° to 5° and plantarflexion remained unchanged from its preoperative range of 20°. The American Orthopaedic Foot & Ankle Society ankle-hindfoot score improved from 38 to 80 points. To the best of our knowledge, this is the first reported case of an alumina-ceramic total ankle prosthesis loosening caused by metallosis resulting from screw abrasion. Favorable treatment results were obtained by using a total talar prosthesis in the revision surgery.

[Hypoxia epigenetically bestows astrocytic differentiation potential on human pluripotent cell-derived neural stem/precursor cells].

The central nervous system (CNS) is composed of three major cell types, neurons, astrocytes, and oligodendrocytes, which differentiate from common multipotent neural stem/precursor cells (NS/PCs). However, NS/PCs do not have this multipotentiality from the beginning: neurons are generated first and astrocytes are later during CNS development. This developmental progression is observed in vitro by using human (h) NS/PCs derived from pluripotent cells, such as embryonic- and induced pluripotent-stem cells (ES/iPSCs), however, in contrast to rodent's pluripotent cells, they require quite long time to obtain astrocytic differentiation potential. Here, we show that hypoxia confers astrocytic differentiation potential on hNS/PCs through epigenetic alteration for gene regulation. Furthermore, we found that these molecular mechanisms can be applied to functional analysis of patient' iPSC-derived astrocytes. In this review, we summarize recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NS/PC fate and the development of potential therapeutic strategies for treating astrocyte-mediated neurological disorders.

Cooperation of PU.1 With IRF8 and NFATc1 Defines Chromatin Landscapes During RANKL-Induced Osteoclastogenesis.

Receptor activator of nuclear factor κB ligand (RANKL) induces osteoclast (OC) differentiation from bone marrow-derived macrophages (BMMs). The transcription factors nuclear factor of activated T cells 1 (NFATc1) and interferon regulatory factor (IRF) 8 play positive and negative roles, respectively, in this process. However, genomewide mapping of the active cis-regulatory elements regulating OC differentiation has not been performed, and little is known about the global landscape of OC-specific gene regulation. We used chromatin immunoprecipitation and formaldehyde-assisted isolation of regulatory elements followed by sequencing to show that PU.1 transcription factor binding motifs were overrepresented at active cis-regulatory regions in both murine BMMs and OCs, while IRF and NFAT binding motifs were selectively enriched at these regions in BMMs and OCs, respectively. We also found that RANKL induced the downregulation of Irf8 and upregulation of Nfatc1 expression, which was associated with dramatic alterations in histone modification. BMM-specific PU.1 binding sites were observed to overlap with IRF8 binding sites in BMMs, and this also occurred for OC-specific PU.1 binding sites and NFATc1 binding sites in OCs. The expression of genes with IRF8 peaks within BMM-specific PU.1 binding sites was significantly higher in BMMs than in OCs, while that of genes with NFATc1 peaks within OC-specific PU.1 binding sites was significantly higher in OCs than in BMMs. Our results suggest that PU.1 switches its transcription partner from IRF8 to NFATc1 and alters the binding regions during RANKL-induced osteoclastogenesis, which is associated with changes in epigenetic profiles and the control of cell type-specific gene expression. © 2019 American Society for Bone and Mineral Research.

Evaluation of the Effects of Chronic Kidney Disease and Hemodialysis on the Inner Ear Using Multifrequency Tympanometry.

OBJECTIVES: To evaluate the effects of chronic kidney disease (CKD) and hemodialysis (HD) on the inner ear using the G width (the width between the bimodal peaks of the conductance (G) tympanogram at 2,000 Hz), which reflects the inner ear pressure and/or the existence of endolymphatic hydrops. MATERIALS AND METHODS: We selected five patients (10 ears) from the patients with CKD who were hospitalized for creation of arteriovenous fistula prior to initiation of HD (non-HD group), and we selected seven patients (14 ears) from the patients with CKD who were undergoing HD (the HD group). As a control group, we selected 80 healthy individuals (160 ears); these were mainly the medical staff of the hospital. We measured the G width of the control group and that of patients with CKD using multifrequency tympanometry. RESULTS: The mean G widths of the HD (measured just before an HD session), non-HD, and control groups were 210.7, 128.4, and 97.0 daPa, respectively. The G width of the HD group was significantly greater than that of the control and non-HD groups (p<0.01 and p<0.01, respectively; Tukey-Kramer test after one-way analysis of variance). The non-HD group also had a greater G width than the control, but it was not significant (p=0.20; Tukey-Kramer). No significant changes were observed in the G widths of the HD group, just before and after a single HD session (p=0.423; paired t-test). CONCLUSION: The greater G width observed in hemodialyzed CKD patients suggests either an increased inner ear pressure or the existence of endolymphatic hydrops in these patients, which is probably related to their otologic symptoms.

Prior Treatment with Anti-High Mobility Group Box-1 Antibody Boosts Human Neural Stem Cell Transplantation-Mediated Functional Recovery After Spinal Cord Injury.

Together with residual host neurons, transplanted neural stem cell (NSC)-derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern protein that triggers sterile inflammation after tissue injury. In the ischemic and injured brain, neutralization of HMGB1 with a specific antibody reportedly stabilizes the blood-brain barrier, suppresses inflammatory cytokine expression, and improves functional recovery. Using a SCI model mouse, we here developed a combinatorial treatment for SCI: administering anti-HMGB1 antibody prior to transplantation of NSCs derived from human induced pluripotent stem cells (hiPSC-NSCs) yielded a dramatic improvement in locomotion recovery after SCI. Even anti-HMGB1 antibody treatment alone alleviated blood-spinal cord barrier disruption and edema formation, and increased the number of neurites from spared axons and the survival of host neurons, resulting in functional recovery. However, this recovery was greatly enhanced by the subsequent hiPSC-NSC transplantation, reaching an extent that has never before been reported. We also found that this improved recovery was directly associated with connections established between surviving host neurons and transplant-derived neurons. Taken together, our results highlight combinatorial treatment with anti-HMGB1 antibody and hiPSC-NSC transplantation as a promising novel therapy for SCI. Stem Cells 2018;36:737-750.