Optimal Body Weights for Adults with Severe Motor and Intellectual Disabilities.

Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)2×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.

Decision Tree Analysis Accurately Predicts Discharge Destination After Spinal Cord Injury Rehabilitation.

OBJECTIVES: To predict discharge destination after spinal cord injury (SCI) rehabilitation. STUDY DESIGN: A retrospective, single-center study. We collected the following data from medical charts: age, sex, living arrangement before injury, acute length of stay (LOS), level of injury on admission, American Spinal Injury Association Impairment Scale (AIS) on admission, Upper Extremity Motor Score (UEMS) on admission, Lower Extremity Motor Score on admission (LEMS), Spinal Cord Independence Measure (SCIM) scores on admission and discharge, and discharge destination. A decision tree algorithm was used to establish prediction models in a train-test split manner using features on admission or discharge. SETTING: A spinal center in Tokyo, Japan. PARTICIPANTS: Participants were individuals with SCI admitted to our hospital from March 2016 to October 2021 for the first rehabilitation after the injury. The study included 210 participants divided into 2 groups: training (n=140) and testing (n=70). Random sampling without replacement was used. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prediction accuracy was evaluated with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating curve (AUC). RESULTS: AIS was significantly different between the groups. The prediction model using total SCIM scores on discharge (D-Classification and Regression Tree [CART]) revealed that a cut-off value of 40 accurately predicted the discharge destination. In contrast, the prediction model using features on admission (A-CART) revealed that subtotal SCIM mobility scores of 5, age of 74 years, and UEMS of 23 were significant predictors. Sensitivity, specificity, PPV, NPV, and AUC of D-CART and A-CART were 0.837, 0.810, 0.911, 0.680, and 0.832 and 0.857, 0.810, 0.913, 0.708, and 0.869, respectively. CONCLUSIONS: D-CART and A-CART showed comparable prediction accuracies. This suggests that, even during the early stages of rehabilitation, it is possible to predict the discharge destination.

Functional Outcome Prediction After Spinal Cord Injury Using Ensemble Machine Learning.

OBJECTIVES: To establish a machine learning model to predict functional outcomes after SCI with Spinal Cord Independence Measure (SCIM) using features present at the time of rehabilitation admission. STUDY DESIGN: A retrospective, single-center study. The following data were collected from the medical charts: age, sex, acute length of stay (LOS), level of injury, American Spinal Injury Association Impairment Scale (AIS), motor scores of each key muscle, Upper Extremity Motor Score (UEMS), Lower Extremity Motor Score (LEMS), SCIM total scores, and subtotal scores on admission and discharge. Based on the multivariate linear regression analysis, age, acute LOS, UEMS, LEMS, and SCIM subtotal scores were selected as features for machine learning algorithms. Random forest, support vector machine, neural network, and gradient boosting were used as the base models and combined using ridge regression as a metamodel. SETTING: A spinal center in Tokyo, Japan. PARTICIPANTS: Participants were individuals with SCI admitted to our hospital from March 2016 to October 2021 for the first rehabilitation after the injury. They were divided into 2 groups: training (n=140) and testing (n=70). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The root-mean-square error (RMSE), R2, and Mean Absolute Error (MAE) were used as accuracy measures. RESULTS: RMSE, R2, and MAE of the meta-model using the testing group were 9.7453, 0.8835, and 7.4743, respectively, outperforming any other single base model. CONCLUSIONS: Our study revealed that functional prognostication could be achieved using machine-learning methods with features present at the time of rehabilitation admission. Goals can be set at the beginning of rehabilitation. Moreover, our model can be used to evaluate advanced medical treatments, such as regenerative medicine.

Evaluation of eGFRs to Calculate Kidney Function in Adults with Severe Motor and Intellectual Disabilities.

Introduction: The gold standard for evaluating kidney function is kidney inulin clearance (Cin). However, this procedure is difficult to perform in patients with neuromuscular disabilities and/or bladder dysfunction. We aimed to develop a simpler method for determining the estimated glomerular filtration rate (eGFR) using equations and values for three biomarkers: serum creatinine (sCr), serum cystatin C (cysC), and serum beta-2 microglobulin (ß2MG). This study evaluated three eGFR equations in patients with severe motor and intellectual disabilities (SMID). Methods: We evaluated the equations using data of 18 adult SMID patients with a clinical need for creatinine clearance (Ccr). We compared the results of each equation with Ccr-based eGFR instead of Cin using mean error (ME), root mean square error (RMSE), and P30. Results: Based on eGFR, the ME values of Cr, cysC, ß2MG, and Ccr were 74.5, 2.3, and 6.5 mL/min/1.73 m2, RMSE values, 92.3, 25.7, and 33.4 mL/min/1.73 m2; and P30, 16.7%, 77.8%, and 72.2%, respectively. Conclusions: eGFR-Cr cannot be used to reliably assess kidney function in adult SMID patients. It is better to use eGFR-cysC to evaluate kidney function in this patient population.

Reference blood pressure values obtained using the auscultation method for 2-year-old Japanese children: from the Japan Environment and Children's Study.

BACKGROUND: Reference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established. METHODS: This was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children's Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda-mu-sigma (LMS) method and compared with those obtained via the polynomial regression model. RESULTS: Data from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively. CONCLUSION: The reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available.

Analysis of the ratio of urinary beta-2-microglobulin to total protein concentration in children with isolated tubulointerstitial disease.

BACKGROUND: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (ß2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary ß2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary ß2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. METHODS: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary ß2-MG levels were > 1000 µg/L. Urinary ß2-MG and TP concentrations were obtained, and the ratio of urinary ß2-MG to TP concentration (µg/mg) was calculated. The Mann-Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. RESULTS: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary ß2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. CONCLUSION: In children with tubulointerstitial diseases, the urinary ß2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary ß2-MG to TP concentration of < 22.3 (µg/mg).

Autistic traits of children born very preterm assessed using Autism Diagnostic Observation Schedule, Second Edition.

Preterm birth has been linked with increased incidence of autism spectrum disorder (ASD). Despite the remarkable difference in the clinical backgrounds between ASD children born preterm and term, cross-sectional studies have found no striking difference in their autistic traits. To highlight autistic traits related with preterm birth, children born very preterm (prospective birth cohort, n = 50) and term (case cohort, n = 16), who were diagnosed as "Autism" by the Autism Diagnostic Observation Schedule (ADOS), 2nd edition, were compared using the calibrated severity scores of ADOS-2 and T-scores of the Social Responsiveness Scale, 2nd edition. No significant difference was found in the calibrated severity scores between ASD children born preterm and term. There was a trend that T-scores were smaller for the preterm cohort, which did not reach a statistical significance. Even when detailed cross-sectional information was obtained using ADOS-2, no difference in autistic traits was observed between children born very preterm and term. Our findings were consistent with a previous study, which assessed the entire prospective cohort of children born very preterm and found no difference in original ADOS scores. Further studies are warranted to delineate how preterm birth affects the autistic traits and their parental perception in a large prospective cohort.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. METHODS: We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. RESULTS: Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR<90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). CONCLUSIONS: Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

Urine alpha 1-microglobulin-to-creatinine ratio and beta 2-microglobulin-to-creatinine ratio for detecting CAKUT with kidney dysfunction in children.

BACKGROUND: The leading cause of advanced chronic kidney disease (CKD) in children is congenital anomalies of the kidney and urinary tract (CAKUT). However, the most appropriate parameters of biochemical urine analysis for detecting CAKUT with kidney dysfunction are not known. METHODS: The present observational study analyzed data on children with CAKUT (stage 2-4 CKD) and the general pediatric population obtained from school urine screenings. The sensitivity and specificity of urine alpha 1-microglobulin-, beta 2-microglobulin-, protein-, and the albumin-to-creatinine ratios (AMCR, BMCR, PCR, ACR, respectively) in detecting CAKUT with kidney dysfunction were compared with those of the conventional urine dipstick, and the most appropriate of these four parameters were evaluated. RESULTS: In total, 77 children with CAKUT and 1712 subjects in the general pediatric population fulfilled the eligibility criteria. Conventional dipstick urinalysis was insufficient due to its low sensitivity; even when the threshold of proteinuria was +/-, its sensitivity was only 29.7% for stage 2 and 44.1% for stage 3 CKD. Among the four parameters assessed, the AMCR and BMCR were adequate for detecting CAKUT in children with stage 3-4 CKD (the respective sensitivity and specificity of the AMCR for detecting CAKUT in stage 3 CKD was 79.4% and 97.5% while that of BMCR was 82.4% and 97.5%). These data were validated using national cohort data. CONCLUSION: AMCR and BMCR are superior to dipstick urinalysis, PCR, and ACR in detecting CAKUT with kidney dysfunction, particularly stage 3 CKD. However, for AMCR, external validation is required. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

BACKGROUND: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. METHODS: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded. RESULTS: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. CONCLUSIONS: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ultrasonographic reference values and a simple yet practical formula for estimating average kidney length in Japanese children.

BACKGROUND: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants. METHODS: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis. RESULTS: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]". CONCLUSION: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established.

Urodynamic effect of vibegron on neurogenic lower urinary tract dysfunction in individuals with spinal cord injury: A retrospective study.

STUDY DESIGN: A Retrospective study. OBJECTIVES: To investigate the effects of vibegron on urodynamic parameters of individuals with spinal cord injury (SCI). SETTING: The National Hospital Organization, Murayama Medical Center, Japan. METHODS: We retrospectively analyzed the urodynamic parameters of 31 individuals with SCI within one year after injury, who were diagnosed with neurogenic lower urinary tract dysfunction (NLUTD) according to a urodynamic study (UDS), and prescribed vibegron between December 2018 and December 2020. Treatment criteria were as follows: cystometric capacity of <200 mL, bladder compliance of <20 mL/cmH2O, and/or presence of detrusor overactivity in the first UDS. We compared urodynamic data before and after vibegron treatment. RESULTS: Vibegron administration increased the maximum cystometric capacity (MCC) (median, from 185.0 to 340.0 mL, P = 0.001), bladder compliance (median, from 8.3 to 20.0 mL/cmH2O, P < 0.001). CONCLUSION: Vibegron therapy improved the bladder capacity and bladder compliance of individuals with NLUTD and SCI.

Validation of the estimated glomerular filtration rate equation for Japanese children younger than 2 years.

BACKGROUND: We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFRUemura). The eGFR equation is for children aged 2-18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFRunder 2). The aim of the present study was to validate this new equation. METHODS: We collected the data of 13 patients from previous studies and compared the results of eGFRunder 2, eGFRUemura, and updated eGFR developed by Schwartz (eGFRSchwartz) with measured GFR using mean error (ME), root mean square error (RMSE), P30 and Bland-Altman analysis. RESULTS: The ME of eGFRunder 2, eGFRUemura and eGFRSchwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m2, respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland-Altman bias analysis showed fan-shape. The eGFRunder 2 equation was the most accurate in the three equations. CONCLUSION: The eGFRunder 2 equation was useful for Japanese children younger than 2 years.

Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin.

BACKGROUND: There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients. METHODS: Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin). RESULTS: Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study. CONCLUSIONS: The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. CLINICALTRIALS. GOV IDENTIFIER: NCT03345316.

Serum albumin level is associated with mycophenolic acid concentration in children with idiopathic nephrotic syndrome.

Mycophenolate mofetil is effective for the treatment of pediatric idiopathic nephrotic syndrome (INS). The dosage of mycophenolate mofetil is adjusted according to the serum concentration of mycophenolic acid (MPA). Kidney function or cyclosporine (CsA) concentrations affect serum MPA levels. However, few studies have focused on the association between serum concentrations of MPA and albumin. This retrospective observational study aimed to evaluate the relationship between the serum concentrations of MPA and albumin in INS children. Subjects were children with INS who underwent the therapeutic drug monitoring of CsA and MPA. We obtained the serum albumin (sAlb) concentration, estimated glomerular filtration rate (eGFR), age, and MPA and CsA areas under concentration-time curves from 0 to 12 h (AUC0-12). Multiple linear regression analysis and generalized estimating equations were performed to predict values for MPA AUC0-12. We obtained information for 51 INS children with 261 MPA AUC0-12 measurements. The standardized regression coefficients of sAlb, eGFR, CsA AUC0-12, and age were 0.54, - 0.21, - 0.07, and 0.04, respectively. Furthermore, MPA AUC0-12 levels positively correlated with sAlb concentrations (p < 0.001) and were inversely correlated with eGFR values (p = 0.005) but not with CsA AUC0-12 (p = 0.24) and age (p = 0.65).Conclusion: Serum albumin concentration was strongly associated with total MPA concentration compared with kidney function or CsA values. Although patients with INS may have a low serum concentration of total MPA in the presence of low sAlb concentration, close attention should be paid to the interpretation of the low MPA values. What is Known: • The dosage of mycophenolate mofetil is adjusted according to the serum concentration of total mycophenolic acid. • Kidney function, cyclosporin concentrations, or serum albumin concentrations influence serum mycophenolic acid levels. What is New: • Serum albumin concentration is more strongly associated with total mycophenolic acid concentration than kidney function or cyclosporin values. • In children with nephrotic syndrome, the total mycophenolic acid concentration may not increase in the presence of severe hypoalbuminemia.

Diagnostic rate of autism spectrum disorder in a high-survival cohort of children born very preterm: A cross-sectional study.

To investigate the diagnostic rate of autism spectrum disorder (ASD) in a high-survival cohort of very preterm children, 77 infants born very preterm (<32 weeks of gestation) were assessed at age 4-6 years old using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Sixteen children (20.8%) were classified as both DSM-5-positive ASD and ADOS-2-identified "autism," which were defined as confirmed ASD in this study. Our result suggests that the prevalence of ASD in very preterm children might be much higher than reported in previous studies when all children were individually evaluated. Further studies in a large sample are required to clarify the true risk of ASD in preterm birth.

Perinatal factors contributing to intellectual impairment in a cohort of Japanese children with very low birth weight.

BACKGROUND: To determine whether prematurity, intrauterine growth restriction (IUGR), or neonatal stress affects intellectual impairment in children with very low birth weight (VLBW). METHODS: This national historical cohort study evaluated children with VLBW cared for in perinatal medical centers throughout Japan. Factors assessed included three latent variables (prematurity, IUGR, and stress during the neonatal period) and eight observed variables during perinatal period. The primary endpoint was intellectual or developmental quotient (IQ/DQ) at age ≥3 years. Structural equation model (SEM) was used to examine factors associated with IQ/DQ. RESULTS: The study included 248 VLBW children, who were of mean age 5.7±2.0 years and mean IQ/DQ of 85.5 at last encounter. SEM showed that stress during the neonatal period (ß=-0.37) contributed more to IQ/DQ than intrauterine malnutrition (ß=0.25) and prematurity (ß=0.15) and that the duration of mechanical ventilation was an important contributor to stress during the neonatal period. CONCLUSIONS: Neonatal stress was more harmful to future intellectual impairment of VLBW neonates, with IUGR contributing more than prematurity. Duration of mechanical ventilation was an important risk factor in neonatal stress. Neonatologists should minimize neonatal stress in VLBW neonates, and obstetricians should monitor fetal growth restriction to prevent intellectual impairment in later life.

Current progress of rehabilitative strategies in stem cell therapy for spinal cord injury: a review.

Stem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.