The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial.

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Efficacy of rituximab therapy in children with nephrotic syndrome: a 10-year experience from an Iranian pediatric hospital.

BACKGROUND: There are controversy results in the optimal management of children with steroid-dependent and steroid-resistant nephrotic syndrome (SDNS, SRNS). This study aimed to determine the efficacy and safety of rituximab (RTX) in these pediatric patients. METHODS: Medical records of 1-18-year-old Iranian children with SDNS (n = 26) and SRNS (n = 22) with a follow-up for at least 24 months were included from 2009 to 2019. The short- and long-term responses to RTX were respectively evaluated to determine the random protein-to-creatinine ratio after 6 and 24 months and classified as complete (CR) and partial (PR) remission or no response. RESULTS: Male patients (n = 26) were slightly predominate. The median age of patients at the time of RTX therapy was 8.6 ± 4.01 years. At the end of the 6-month follow-up, CR and PR occurred in 23 (47.9%) and 12 (25%) patients, respectively. Of 23 patients with CR, 18 (69.2%) and 5(22.7%) had SDNS and SRNS, respectively (p < 0.005). However, only 18 (37.5%) of patients after 24 months had been in CR. No significant difference in the CR rate was found between the two groups. RTX was more effective when administered during the proteinuria-free period (p = 0.001). CONCLUSION: In the short term, RTX significantly was efficient in inducing complete or PR in SDNS and SRNS patients. However, the favorable response rate in a long-term follow-up was insignificantly lower between the two groups.

Clinical manifestations, laboratory markers, and renal ultrasonographic examinations in 1-month to 12-year-old Iranian children with pyelonephritis: a six-year cross-sectional retrospective study.

BACKGROUND: Upper urinary tract infection (UTI) or pyelonephritis may increase the pathogenesis rate and risk of severe complications in children due to kidney atrophy. OBJECTIVE: A set of clinical symptoms, laboratory markers, and ultrasound findings were assessed to achieve the early diagnosis and prognosis of pyelonephritis in hospitalized pediatrics. METHODS: A cross-sectional study with 104 Iranian children (95 girls and 9 boys) aged 1 month to 12 years with acute pyelonephritis during 2012-2018 was conducted. The ultrasound examination of kidneys and urinary tract during hospitalization, the incidence of clinical symptoms, and laboratory markers in blood and urine were monitored to identify the best predictive factors of early diagnosis of this bacterial infection. RESULTS: Three-fourth of the patients had one of the four clinical symptoms of abdominal pain, constipation, dysuria, and vomiting, while others were asymptomatic. A much frequency of pyuria (88.46%), Escherichia coli in urine (92.31%), leukocytosis (81.73%), and high ESR (> 10 mm/h, 92.30%) and CRP (> 10 mg/L, 82.82%) was observed. The kidney and urinary tract ultrasonography only in 32.7% of children revealed findings in favor of pyelonephritis (cystitis, ureteral stones, and hydronephrosis). CONCLUSION: There was a high frequency of clinical signs and laboratory markers associated with pyelonephritis. Ultrasound alone was not an efficient tool to track febrile UTI as most patients presented normal sonography.

Relationship of Urinary Tract Infection to Lower Urinary Tract Dysfunction and Kidney Scar Formation in Children.

BACKGROUND: Urinary tract infection (UTI) is the most common infection during childhood. Lower urinary tract dysfunction (LUTD) is a broad term that indicates an abnormal voiding pattern in a child without anatomical and neurological impairment. The purpose of this study was to determine the relationship between UTI and LUTD. METHODS: This study was conducted at the Children Medical Center Hospital in 2014-2016. The inclusion criteria of this study were at least one UTI confirmed by a positive urine culture and active urine analysis in children who were well toilet-trained previously. Complete physical examination of the genitourinary and skeletal systems was performed to identify patients with anomalies in these systems. The patients with genitourinary system anomalies and obvious and prediagnosed neurological defects of the urinary system such as neurogenic bladder were excluded from the study. To confirm the presence of LUTD, the scoring system of Akbal et al. was applied. RESULTS: A total of 260 patients including 9.2% of males and 90.8% of females were included in this study. The prevalence of LUTD was 63.8% (166 cases) in these patients. In this study, the prevalence of LUTD in patients with a single episode of UTI was 50.5%, while in patients with recurrence of UTI it was 88.9%. In patients with unilateral kidney scar formation, 90.9% had a recurrence of UTI (P = 0.003) which shows a strong correlation of unilateral scar formation with recurrence of UTI. CONCLUSIONS: These data suggest that there is a significant relationship between UTI and LUTD in children, so evaluation of voiding dysfunction is necessary in this group. With early diagnosis and appropriate treatment, we can reduce the possible serious and permanent sequels of LUTD in patients with UTIs.