A spinal cord injury (SCI) is a destructive event that causes a permanent deficit in neurological function because of poor regenerative potential. Transplantation therapies have attracted attention ...for restoration of the injured spinal cord, and transplantation of neural precursor cells (NPCs) has been studied worldwide. Several groups have demonstrated functional recovery via this therapeutic intervention due to the multiple beneficial effects of NPC transplantation, such as reconstruction of neuronal circuits, remyelination of axons, and neuroprotection by trophic factors. Our group developed a method to induce NPCs from human induced pluripotent stem cells (hiPSCs) and established a transplantation strategy for SCI. Functional improvement in SCI animals treated with hiPSC-NPCs was observed, and the safety of transplanting these cells was evaluated from multiple perspectives. With selection of a safe cell line and pretreatment of the cells to encourage maturation and differentiation, hiPSC-NPC transplantation therapy is now in the clinical phase of testing for subacute SCI. In addition, a research challenge will be to expand the efficacy of transplantation therapy for chronic SCI. More comprehensive strategies involving combination treatments are required to treat this problematic situation.
Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon ...be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI.
•The neuronal activity of hM4Di-NS/PCs was controlled by CNO administration•Inhibiting the neuronal activity of grafted NS/PCs led to functional decline•Grafted neurons derived from hiPSC-NS/PCs integrated into host motor circuits
This study by Okano, Nagoshi, and colleagues demonstrated decreased locomotor function in hiPSC-NS/PC-transplanted SCI mice induced by inhibition of graft-derived neuronal activity using a DREADD. Locomotor changes caused by the graft neuronal activity inhibition were observed exclusively in the chronic phase. These results suggested the significance of engrafting functionally mature neurons via hiPSC-NS/PC transplantation for behavioral improvement following SCI.
The Wnt/
β
-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound ...inhibiting the Wnt/
β
-catenin signaling pathway, named LPD-01 (
1
), and
1
inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that
1
inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of
1
in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/
β
-catenin signaling pathway
-
related proteins. As a result,
1
inhibited the expression of target proteins of Wnt/
β
-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (
β
-catenin) was not decreased, suggesting that
1
inhibited the Wnt/
β
-catenin signaling pathway without affecting β-catenin. Next, we investigated the target proteins of
1
using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that
1
directly binds to importin7. As expected,
1
inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-
β
-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/
β
-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of
1
for inhibition of the Wnt/
β
-catenin signaling pathway.
Graphical abstract
•MCIDs are disease- and procedure-specific.•No MCIDs of major PROMs specific to LSS undergoing decompression were reported.•MCIDs of the NRS, RMDQ, and SF-8 specific to LSS after decompression were ...identified.•MCIDs of NRS was 2 points for back pain, 2–4 points for leg pain and numbness.•MCID was 3–5 points for RMDQ, 5–6 points for PCS, and 2–6 points for MCS.
A minimum clinically important difference (MCID) has been increasingly well known in the current era of patient-centered care because it reflects a smallest change that is meaningful for patients following a clinical intervention. Previous studies suggested MCID values are disease and/or procedure dependent. No MCID values have been reported on the lumbar spinal stenosis (LSS) following decompression surgery despite LSS is the most common spinal disease and the main treatment is decompression surgery. Therefore, this study aimed to determine the MCID values as major outcome measures including the Numeric Rating Scale (NRS) of back pain, leg pain and numbness, Roland-Morris Disability Questionnaire (RMDQ), and Physical Component Summary (PCS) and Mental Component Summary (MCS) of Short Form 8 (SF-8) for patients with LSS undergoing decompression surgery.
This is a retrospective cohort study using prospectively collected data from consecutive patients who underwent lumbar decompression without fusion for LSS at a single institution between May 2014 and March 2016. Inclusion criteria were 1) minimum 1-year follow-up 2) a complete set of preoperative and final follow-up questionnaires available, including the NRS, RMDQ, and SF-8. Revision surgery or non-degenerative etiology such as infection or tumor was excluded. MCIDs of each outcome measure were determined using two major approaches, distribution- and anchor-based methods. The distribution-based method uses the distributional characteristics of the sample. This method expresses the observed degree of variation to obtain a standardized metric such as the standard deviation or standard error of measurement. The anchor-based method uses an external criterion known as anchor to determine the factors that should be considered by patients for an important improvement. Anchor-based methods assess how much changes in the measurement instrument correspond with a minimal important change defined on the anchor. We used symptom severity, physical function, and satisfaction scores from Zurich Claudication Questionnaire as anchors for NRS and RMDQ, PCS, and MCS, respectively.
A total of 126 patients were included. From the anchor-based method, MCIDs were determined to be 2 points for back pain, 4 points for leg pain and numbness, 5 points for RMDQ, 5 points for PCS, and 2 points for MCS. From the distribution-based method, MCIDs were determined to be 2 points for back pain, leg pain and numbness, 3–4 points for RMDQ, 6 points for PCS, and 5 points for MCS.
We first identified the MCIDs of the NRS, RMDQ, and SF-8 specific to patients undergoing decompression surgery for LSS.
Various olefins can be hydrogenated quantitatively with neutral flavin 2 catalysts in the presence of 1−2 equiv of hydrazine under 1 atm of O2. Vitamin B2 derivative 2g acts as a highly efficient and ...robust catalyst for the present environmentally benign process producing water and nitrogen gas as the only waste products.
•Impact of postoperative residual numbness on patient satisfaction has not been well studied.•Residual numbness had a greater impact than leg/back pain on patient satisfaction.•We suggest not only ...back and leg pain but also numbness should be evaluated pre- and postoperatively.
Decompression surgery is the most common surgical treatment for lumbar spinal stenosis (LSS). Relatively low satisfaction rate was reported. Patients often complaint of residual numbness despite significant pain relief. We hypothesized that numbness had a significant impact on patient satisfaction, but had not been evaluated, which is associated with low satisfaction rate. This study aimed to examine how much numbness is associated with patient satisfaction.
We retrospectively reviewed prospectively collected data from consecutive patients who underwent decompression without fusion for LSS. We evaluated the Numeric Rating Scale (NRS) scores of low back pain (LBP), leg pain, and leg numbness preoperatively and at the final follow-up visit. Improvement was evaluated using minimum clinically important differences (MCIDs). Patient satisfaction was evaluated using the question, “How satisfied are you with the overall result of your back operation?”. There are four possible answers consisting of “very satisfied (4-point)”, “somewhat satisfied (3-point)”, “somewhat dissatisfied (2-point)”, or “very dissatisfied (1-point)”. Spearman correlation was used to evaluate the association between patient satisfaction and reaching MCIDs.
A total of 116 patients were included. All three components had correlation with patient satisfaction with the correlation efficient of 0.30 in LBP, 0.22 in leg pain, and 0.33 in numbness. Numbness had greatest correlation efficient value.
We showed that numbness has a greater impact than leg/back pain on patient satisfaction in patients undergoing decompression for LSS. We suggest not only LBP and leg pain but also numbness should be evaluated pre- and postoperatively.
Study Design: This is a retrospective case series study. Objective: The aim of this study was to investigate whether frailty contributes to functional recovery in individuals with spinal cord injury ...(SCI). Methods: A total of 121 patients with SCI (106 cervical SCI, 15 thoracic SCI) discharged from our center over the past three years were studied. Moreover, 11-factor modified frailty index (mFI) scores, the length of hospital stays, the rate of returning home, and improvement in Spinal Cord Independence Measure (SCIM) scores were assessed retrospectively. Results: The average age at the time of injury for all 121 cases was 59.6 years. Based on pre-injury assessments, 24 cases were categorized as the Frail group, and 97 cases were categorized as the Robust group. The Frail group had SCIM improvement rates of 16.7% and a home discharge rate of 45.8%. In contrast, the Robust group had SCIM improvement rates of 33.5% and a home discharge rate of 68.0%, with statistically significant differences between the two groups. A significant negative correlation was observed between mFI scores and SCIM improvement rates (R = −0.231, p = 0.014). Conclusions: This study suggests that individuals with pre-existing frailty before SCI experience poorer SCIM improvement rates and face challenges in returning home.
Background: This study aims to investigate the postoperative improvement of paralysis, fusion rate and risk factors for kyphosis progression in adults affected with spinal caries. Methods: Overall, ...134 patients with spinal caries from the thoracic to lumbar spine from 1992 to 2021 were included in this study. Data concerning the affected level (thoracic, thoracolumbar, lumbar, and lumbosacral), bone fusion rate, and progression of the postoperative local kyphosis angle were collected. The risk factors for the progression of local kyphosis angle after anterior spinal fixation (ASF) were determined using linear regression analysis. Results: Preoperatively, the degree of spinal cord paralysis was D and E on Frankel classification. Improvement of paralysis was good with surgery, especially from C, D. The overall bone fusion rate was 83.2%. The only factor influencing the progression of local kyphosis angle after ASF was the level of the affected vertebra. Progression of kyphosis angle after ASF was very advanced in the thoracolumbar transition area. Conclusions: Surgical improvement in paraplegia and the fusion rate of ASF with only grafted bone was good. However, in patients affected in the thoracolumbar spine region, posterior instrumentation is desirable because of local kyphosis progression risk after surgery.
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