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Study design. A prospective cohort study. Objectives. Thrombin-gelatin matrix (TGM) is a rapid and potent hemostatic agent, but it has some limitations, including the cost and its preparation time. The purpose of this study was to investigate the current trend in the use of TGM and to identify the predictors for TGM usage in order to ensure its proper use and optimized resource allocation. Methods. A total of 5520 patients who underwent spine surgery in a multicenter study group within a year were included in the study. The demographic factors and the surgical factors including spinal levels operated, emergency surgery, reoperation, approach, durotomy, instrumented fixation, interbody fusion, osteotomy, and endoscopy were investigated. TGM usage and whether it was routine or unplanned use for uncontrolled bleeding were also checked. A multivariate logistic regression analysis was used to identify predictors for unplanned use of TGM. Results. The mean age was 63.5 years old, and males accounted for 59.9% of patients. The mean operation time was 147 minutes, median blood loss was 50mL, and interquartile range was 145mL. Intraoperative TGM was used in 1934 cases (35.0%), among which 714 were unplanned (12.9%). Predictors of unplanned TGM use were female gender, cervical spine, tumor, posterior approach, durotomy, instrumentation, osteotomy, and endoscopy. Conclusions. Many of the predictors for unplanned TGM use have been previously reported as risk factors for intraoperative massive hemorrhaging and blood transfusion. However, other newly revealed factors can be predictors of bleeding that is technically challenging to control.

Background Decline in cognitive function after night shift has been well described. However, in the field of spine surgery, the effect of surgeons’ sleeplessness on patient outcome is unclear. The purpose of this study was to investigate whether the risk of perioperative complications in elective thoracolumbar spine surgery could be higher if the surgeon had been on a night shift prior to the day of surgery. Methods We performed a retrospective review of patients who underwent elective posterior thoracolumbar spine surgery, as indicated in medical records, between March 2015 and September 2018. In total, 1189 patients were included and divided into two groups: the post-nighttime (n = 110) and control groups (n = 1079). A post-nighttime case was defined when the operating surgeon was on nighttime duty on the previous night, and other cases were defined as controls. We evaluated the incidence of perioperative complications (surgical site infection, postoperative hematoma, postoperative paralysis, nerve root injury, and dural tear) in both groups. Results Overall, we found no significant difference in the major or minor perioperative complication rates between the two groups, but according to the type of complication, the incidence rate of dural tear tended to be higher in the post-nighttime group (13.6% vs 8.2%, P = 0.074). Multivariate analysis showed that post-nighttime status was an independent risk factor of dural tear (adjusted odds ratio, 2.02; 95% confidence interval [CI], 1.10–3.70; P = 0.023). After stratification by surgical complexity, post-nighttime status was an independent risk factor of dural tear only in the surgeries of 3 levels or more (adjusted odds ratio, 2.81; 95% CI, 1.18–6.67; P = 0.019). Conclusions Post-nighttime status was generally not a risk factor of perioperative complications in elective posterior thoracolumbar spine surgeries, but was an independent risk factor of dural tear, especially in complex cases.

Ectopic endochondral ossification in the tendon/ligament is caused by repetitive mechanical overload or inflammation. Tendon stem/progenitor cells (TSPCs) contribute to tissue repair, and some express lubricin [proteoglycan 4 (PRG4)]. However, the mechanisms of ectopic ossification and association of TSPCs are not yet known. Here, we investigated the characteristics of Prg4-positive ( + ) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct Prg4 + TSPC cluster. The Rspo2 + cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. RSPO2 expression levels in patients with ossification of the posterior longitudinal ligament were lower than those in spondylosis patients, and RSPO2 protein suppressed chondrogenic differentiation of human ligament cells. RSPO2 was induced by inflammatory stimulation and mechanical loading via nuclear factor κB. Rspo2 + cells may contribute to tendon/ligament homeostasis under pathogenic conditions.

Study design A prospective observational study. Objective To evaluate the impact on surgical outcomes of preoperative neuropathic pain (NeP) assessed by the painDETECT questionnaire (PDQ) administered to participants undergoing cervical decompression surgery for degenerative cervical myelopathy (DCM). Methods Participating patients were separated into the Non-NeP group (preoperative PDQ score ≤ 12), and NeP group (score ≥ 13). They were asked to complete a booklet questionnaire, including NRS for pain, the Short Form-12 for PCS and MCS, EQ-5D, NDI, and COMI-Neck, at baseline and 1 year after surgery. The JOA score for DCM and radiological changes were also evaluated. Propensity scores were used for the generalized linear model to adjust the patients’ backgrounds. Results Of the 116 patients recruited, 105 completed the one-year follow-up. In this study, 31 (29.5%) and 74 (70.5%) patients in the NeP and non-NeP groups, respectively, were compared. Except for the higher female ratio in the NeP group (64.6% vs 33.2%, P = .009), preoperative demographic data and surgical factors were not significantly different between both groups. The NeP group showed greater neck/arm/hand NRS scores and worse pre- and postoperative NDI/EQ-5D/COMI-Neck scores at baseline and 1 year after surgery, but this was not significant in the MCS/PCS and JOA scores. Change scores of neck/arm/hand NRS scores and MCS/PCS/NDI/EQ-5D/COMI-Neck scores were not significant between both groups. Conclusions The preoperative NeP, assessed by PDQ, was observed in approximately 30% of patients with DCM who underwent decompression surgery. The presence of NeP was associated with worse pre- and postoperative NDI/EQ-5D/COMI-Neck scores.

Background Microendoscopic laminectomy (MEL), in which a 16-mm tubular retractor with an internal scope is used, has shown excellent surgical results for patients with lumbar spinal canal stenosis. However, no reports have directly compared MEL with open laminectomy. This study aimed to elucidate patient-reported outcomes (PROs) and perioperative complications in patients undergoing MEL versus open laminectomy. Methods This is a multicenter retrospective cohort study of prospectively registered patients who underwent lumbar spinal surgery at one of the six high-volume spine centers between April 2017 and September 2018. A total of 258 patients who underwent single posterior lumbar decompression at L4/L5 were enrolled in the study. With regard to demographic data, we prospectively used chart sheets to evaluate the diagnosis, operative procedure, operation time, estimated blood loss, and complications. The follow-up period was 1-year. PROs included a numerical rating scale (NRS) for lower back pain and leg pain, the Oswestry Disability Index (ODI), EuroQol 5 Dimension (EQ-5D), and patient satisfaction with the treatment. Results Of the 258 patients enrolled, 252 (97%) completed the 1-year follow-up. Of the 252, 130 underwent MEL (MEL group) and 122 underwent open decompression (open group). The MEL group required a significantly shorter operating time and sustained lesser intraoperative blood loss compared with the open group. The MEL group showed shorter length of postoperative hospitalization than the open group. The overall complication rate was similar (8.2% in the MEL group versus 7.7% in the open group), and the revision rate did not significantly differ. As for PROs, both preoperative and postoperative values did not significantly differ between the two groups. However, the satisfaction rate was higher in the MEL group (74%) than in the open group (53%) (p = 0.02). Conclusions MEL required a significantly shorter operating time and resulted in lesser intraoperative blood loss compared with laminectomy. Postoperative PROs and complication rates were not significantly different between the procedures, although MEL demonstrated a better satisfaction rate.

Although patients with diabetes reportedly have more peripheral neuropathy, the impacts of diabetes on postoperative recovery in pain and patient-reported outcome measures (PROMs) after laminoplasty for cervical spondylotic myelopathy (CSM) is not well characterized. The authors aimed to elucidate the effects of diabetes on neck/arm/hand/leg/foot pain and PROMs after laminoplasty CSM. The authors retrospectively reviewed 339 patients (82 with diabetes and 257 without) who underwent laminoplasty between C3 and C7 in 11 hospitals during April 2017−October 2019. Preoperative Numerical Rating Scale (NRS) scores in all five areas, the Short Form-12 Mental Component Summary, Euro quality of life 5-dimension, Neck Disability Index, and the Core Outcome Measures Index-Neck) were comparable between the groups. The between-group differences were also not significant in NRS scores and PROMs one after surgery. The change score of NRS hand pain was larger in the diabetic group than the nondiabetic group. The diabetic group showed worse preoperative score but greater improvement in the Short Form-12 Physical Component Summary than the nondiabetic group, following comparable score one year after surgery. These data indicated that the preoperative presence of diabetes, at least, did not adversely affect pain or PROMs one year after laminoplasty for CSM.

Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy; however, the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration.The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their in vivo chondrogenic potential was validated through transplantation into a mouse osteochondral defect model.All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse SSCs was observed with supplementation of BMP2 or TGFβ1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGFβ1. Human ASCs showed no obvious chondrogenesis following single stimulation. Mouse SSCs showed the formation of hyaline-like cartilage which had less fibrous components (COL1/3) with supplementation of TGFβ1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGFβ receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGFβ1 or BMP2. In the transplanted site in vivo, mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1-/COL3-) but other cell types mainly formed COL1/3-positive fibrous tissues in line with in vitro reactivity to TGFβ1.Optimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGFβ1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

Background Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy; however, the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration. Methods The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their in vivo chondrogenic potential was validated through transplantation into a mouse osteochondral defect model. Results All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse SSCs was observed with supplementation of BMP2 or TGFβ1, whereas chondrogenesis of mouse ASCs and human SSCs was observed with supplementation of BMP2 not TGFβ1. Human ASCs showed no obvious chondrogenesis following single stimulation. Mouse SSCs showed the formation of hyaline-like cartilage which had less fibrous components (COL1/3) with supplementation of TGFβ1. However, human cells developed COL1/3+ tissues with all treatments. Transcriptomic analysis for TGFβ receptors and ligands of cells prior to chondrogenic induction did not indicate their distinct reactivity to the TGFβ1 or BMP2. In the transplanted site in vivo, mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1−/COL3−) but other cell types mainly formed COL1/3-positive fibrous tissues in line with in vitro reactivity to TGFβ1. Conclusion Optimal chondrogenic factors driving chondrogenesis from somatic stem cells are intrinsically distinct among cell types and species. Among them, the response to TGFβ1 may possibly represent the fate of stem cells when locally transplanted into cartilage defects.

Background: Somatic stem cell transplantation has been performed for cartilage injury, but the reparative mechanisms are still conflicting. The chondrogenic potential of stem cells are thought as promising features for cartilage therapy, however the correlation between their potential for chondrogenesis in vitro and in vivo remains undefined. The purpose of this study was to investigate the intrinsic chondrogenic condition depends on cell types and explore an indicator to select useful stem cells for cartilage regeneration.Methods: The chondrogenic potential of two different stem cell types derived from adipose tissue (ASCs) and synovium (SSCs) of mice and humans was assessed using bone morphogenic protein-2 (BMP2) and transforming growth factor-β1 (TGFβ1). Their reparative potential was also validated through transplantation into a mouse osteochondral defect model.Results: All cell types showed apparent chondrogenesis under the combination of BMP2 and TGFβ1 in vitro, as assessed by the formation of proteoglycan- and type 2 collagen (COL2)-rich tissues. However, our results vastly differed with those observed following single stimulation among species and cell types; apparent chondrogenesis of mouse ASCs, mouse SSCs, and human SSCs was observed with supplementation of BMP2, either BMP2 and TGFβ1, and BMP2, respectively. Human ASCs showed no chondrogenesis following single stimulation. Among human SSCs, two of six donors formed partially COL2-positive tissues in response to TGFβ1. However, unlike mouse cells, human cells showed fibrous components (COL1/3) with all treatments. Mouse SSCs formed hyaline-like cartilage (proteoglycan+/COL2+/COL1-/COL3-) in the transplanted site in vivo, but other cell types mainly formed COL1/3-positive fibrous tissues. Remarkably, only donors that showed chondrogenic response to TGFβ1 in vitro formed partially COL2-positive tissues in vivo. However, the area was mainly composed of COL1/3, indicating fibrous cartilage-like tissues.Conclusion: The chondrogenic response to TGFβ1 may represent the fate of stem cells when locally transplanted into cartilage defects.

Background and objectives: Minimally invasive surgery has become popular for posterior lumbar interbody fusion (PLIF). Microendoscope-assisted PLIF (ME-PLIF) utilizes a microendoscope within a tubular retractor for PLIF procedures, however, there are no published reports that compare Microendoscope-assisted to open PLIF. Here we compare the surgical and clinical outcomes of ME-PLIF with those of open PLIF. Materials and Methods: A total of 155 consecutive patients who underwent single-level PLIF were registered prospectively. Of the 149 patients with a complete set of preoperative data, 72 patients underwent ME-PLIF (ME-group), and 77 underwent open PLIF (open-group). Clinical and radiographic findings collected one year after surgery were compared. Results: Of the 149 patients, 57 patients in ME-group and 58 patients in the open-group were available. The ME-PLIF procedure required a significantly shorter operating time and involved less intraoperative blood loss. Three patients in both groups reported dural tears as intraoperative complications. Three patients in ME-group experienced postoperative complications, compared to two patients in the open-group. The fusion rate in ME-group at one year was lower than that in the open group (p = 0.06). The proportion of patients who were satisfied was significantly higher in the ME-group (p = 0.02). Conclusions: ME-PLIF was associated with equivalent post-surgical outcomes and significantly higher rates of patient satisfaction than the traditional open PLIF procedure. However, the fusion rate after ME-PLIF tended to be lower than that after the traditional open method.

Additional file 5. Gene expression of chondrogenic marker in the mASCs and mSSCs cultured with BMP2, TGFβ1, or their combination at day 14. Data are collected from over three independent lots and presented as a box plot with dot plot.

Additional file 7. Extended data in mouse SSCs transplantation group without in vivo chondrogenesis. (A) In samples which defect site is close to enthesis, host synovial tissue infiltrated to defect site and inhibited in vivo chondrogenesis, but transplanted mSSCs existed within granulation tissue with unspecified state. (B) Synovial infusions must be observed in samples with patellar dislocation. Notably, IHC for GFP implies vessel like structure built by transplanted mSSCs. (C) In the samples with in vivo chondrogenesis, transplanted mSSCs existed with unspecified state in bone marrow region underneath neo cartilage.

Additional file 20. Micro-CT and histological images in the samples transplanted with hSSCs. IHC images for COL2 with red frame have the area positively stained, and images with blue frame were except for quantification because of non-specific staining. IHC images for SOX9 with yellow frame represents the presence of SOX9 positive cells.

Additional file 8. Saf-O and IHC for pSmad1 and pSmad2 of in vivo specimens of transplanted with mSSCs or mASCs. Representative data are shown. Scale bars = 100 μm.

Additional file 14. Pearson correlation analysis between measurements of histological images in chondrogenic pellet cultured with BMP2, TGFβ1, and their combination. (A) Correlation between proteoglycan and COL2 of hSSCs. (B,C) Correlation between fibrous marker and COL2 of hASCs. Each circle represents individual six donors, and circle size reflects standard deviation for the data plotted in Y axis.

Additional file 4. Chondrogenic pellet culture of mASCs and mSSCs in chondrogenic basal media at day 14. Representative data of macroscopic images and histology are shown.

Additional file 6. Histological features for fibrous cartilage or ectopic cartilage development after transplantation with mouse ASCs.

Additional file 9. The alteration of gene expression of TGFβ superfamily receptors (A), ligands, and chondrogenic markers (B) during chondrogenic culture of mSSCs and mASCs. Data are expressed as Mean ± SD for each lot, and each shape of points represent individual lots.

Study Design Retrospective cohort study Objectives Preoperative mental state has been reported as one of the factors affecting the surgical outcomes of spine surgery, but few studies have examined in detail how patients’ mental state is affected by spine surgery. The purpose of this study was to investigate using the Hospital Anxiety and Depression Scale (HADS) whether surgery improves preoperative depression and anxiety in patients with degenerative cervical myelopathy. Methods We investigated patient-reported outcomes (Mental Component Summary, Physical Component Summary of SF-12 Health Survey, and EQ-5D, Neck Disability Index, JOACMEQ, satisfaction with treatment) and HADS one year after surgery, comparing them before and after surgery between April 2017 and February 2020. Among the cases diagnosed as preoperative anxiety and depression, we additionally compared the patient-reported outcomes based on the presence or absence of postoperative improvement in mental state, having also investigated the correlation between patient-reported outcomes and HADS for sub-analysis. Results Among the 99 patients eligible for inclusion in the present study, we found that patient-reported outcomes and the HADS scores improved significantly after surgery. There was a moderate correlation between the amount of change in HADS-D score before and after surgery and the amount of change in NDI (moderate, r = .41), NRS of neck (moderate, r = .46), and JOACMEQ (cervical spine function; moderate, r = .43, upper extremity function; moderate, r = .41, QOL; moderate, r = .41). Conclusions We found that surgical treatment for patients with degenerative cervical myelopathy may improve postoperative anxiety and depression as well as other patient-reported outcomes.

The Hill plot is a well-known criterion of the f-electron element interatomic threshold distance separating the nonmagnetic state from the magnetic state in actinides and lanthanides. We have reinvestigated the Hill plot of Ce compounds using the commercial crystallographic database CRYSTMET, focusing on a relationship between the Ce-Ce distance and the magnetic ordering temperature because a Ce compound with no other magnetic elements rarely has a magnetic ordering temperature that is higher than 20 K. The Hill plot of approximately 730 compounds has revealed that a Ce compound, particularly a ferromagnet, showing a high magnetic ordering temperature would require a short Ce-Ce distance with a suppression of the valence instability of the Ce ion. From the study, we developed interest in Ce2AuP3 with a Curie temperature of 31 K. The ferromagnetic nature of this material has been examined in terms of a doping effect, which suggests a possible increase in magnetic anisotropy energy.

The prognosis of CD20-positive (CD20+) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence is still poor. A standard treatment for CD20+ DLBCL with CNS recurrence in elderly patients has not been established mainly due to adverse effects. We previously reported the efficacy and safety of MIND-E (ranimustine, ifosfamide, procarbazine, dexamethasone, and etoposide) therapy for elderly CD20+ DLBCL patients with CNS recurrence. Here, we report the use of R-MIND-E therapy (rituximab, ranimustine, ifosfamide, procarbazine, dexamethasone and etoposide) in an elderly CD20+ DLBCL patient with CNS recurrence. The patient achieved a complete response according to Revised Response Criteria for Malignant Lymphoma, and treatment-related toxicity was tolerable. R-MIND-E therapy may be a feasible and useful treatment option for elderly CD20+ DLBCL patients with CNS recurrence.

Highlights • The surgical correction of the deformities of the craniovertebral junction (CVJ) remains a challenge due to its complex anatomy. • A combined anterior-posterior approach is sometimes required, especially in patients with rigid CVJ deformities. • Transoral anterior release assisted by CT navigation can be a safe and effective treatment option for rigid complex CVJ deformities. • The identification of the patients’ anatomical features such as occipitoatlantal assimilation is crucial for accurate navigation., Introduction The surgical correction of deformities of the craniovertebral junction (CVJ) remains a challenge due to its complex anatomy. Despite the well-known usefulness of computed tomography (CT) navigation in posterior spinal surgery, it is applied far less frequently in anterior spinal surgery, mainly due to registration difficulties. Presentation of the case Case 1 was a 68-year-old female with rheumatoid arthritis, with a complaint of neck pain, motor weakness, and dysesthesia in the upper extremities. Case 2 was a 61-year-old male with Chiari malformation, with a complaint of neck pain and gait disturbance after a fall. Magnetic resonance imaging (MRI) showed severe atlantoaxial dislocation and multilevel cervical spinal cord compression in both patients. Continuous halo traction failed to reduce atlantoaxial dislocation, even under general anesthesia, and they were treated with combined anterior release and posterior decompression and fixation using CT navigation. Occipitocervical assimilation, which was present in both patients, enabled precise registration for navigation. Discussion The lack of anatomically characteristic landmarks on the vertebral surface makes obtaining accurate registration difficult in anterior CVJ surgery using CT navigation. The remaining mobility in the occipitocervical joint precludes the use of facial or cranial landmarks. However, occipitocervical assimilation, which is not uncommon in patients with CVJ deformities, enables accurate navigation during transoral surgery. Conclusion Transoral anterior release using CT navigation is an effective treatment option for rigid complex CVJ deformities. The accurate identification of the patients' anatomical features such as occipitoatlantal assimilation, is crucial for the conducting accurate preoperative CT-based navigation during transoral surgery.