Combined use of fractional exhaled nitric oxide and bronchodilator response in predicting future loss of asthma control among children with atopic asthma.

BACKGROUND AND OBJECTIVE: Recognition of patients at risk of asthma exacerbation is important for future asthma care and improved outcome. The aim of the present study was to see whether measurements of bronchodilator response (BDR) and fractional exhaled nitric oxide (FeNO) in combination provide prognostic information superior to either measurement alone in children with atopic asthma. METHODS: A total of 201 atopic children aged 8-16 years with intermittent or mild persistent asthma were included. Pulmonary function tests including BDR and FeNO were serially monitored 10 times or more over 2 years when subjects were not receiving controller medications. After completion of monitoring, 1-year observation for a loss of asthma control was performed. RESULTS: During the monitoring period, positive BDRs (≥12% in forced expiratory volume in 1 s (FEV1 ) from pre-bronchodilator value) and FeNO higher than 35 parts per billion (ppb) were observed at least once in 59% and 77% of participants. When analysed as continuous variables, both BDR (hazard ratio (HR): 1.21; 95% CI: 1.04-1.41; P = 0.014) and FeNO (HR: 1.27; 95% CI: 1.09-1.49; P = 0.003) were associated with increased risks for a control loss. Compared with patients showing either positive BDRs (HR: 3.19; 95% CI: 1.05-9.64) or FeNO higher than 35 ppb (HR: 4.70; 95% CI: 1.68-13.11), patients with both findings (HR: 7.08; 95% CI: 2.57-19.49) had greater risks for a control loss. CONCLUSION: These data support that combined use of BDR and FeNO measurements can modify predictive risk obtained from either measurement alone.

High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration.

BACKGROUND: High tibial osteotomy (HTO) is a well-established method for the treatment of medial compartment osteoarthritis of the knee with varus deformity. However, HTO alone cannot adequately repair the arthritic joint, necessitating cartilage regeneration therapy. Cartilage regeneration procedures with concomitant HTO are used to improve the clinical outcome in patients with varus deformity. AIM: To evaluate cartilage regeneration after implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with concomitant HTO. METHODS: Data for patients who underwent implantation of hUCB-MSCs with concomitant HTO were evaluated. The patients included in this study were over 40 years old, had a varus deformity of more than 5°, and a full-thickness International Cartilage Repair Society (ICRS) grade IV articular cartilage lesion of more than 4 cm2 in the medial compartment of the knee. All patients underwent second-look arthroscopy during hardware removal. Cartilage regeneration was evaluated macroscopically using the ICRS grading system in second-look arthroscopy. We also assessed the effects of patient characteristics, such as trochlear lesions, age, and lesion size, using patient medical records. RESULTS: A total of 125 patients were included in the study, with an average age of 58.3 ± 6.8 years (range: 43-74 years old); 95 (76%) were female and 30 (24%) were male. The average hip-knee-ankle (HKA) angle for measuring varus deformity was 7.6° ± 2.4° (range: 5.0-14.2°). In second-look arthroscopy, the status of medial femoral condyle (MFC) cartilage was as follows: 73 (58.4%) patients with ICRS grade I, 37 (29.6%) with ICRS grade II, and 15 (12%) with ICRS grade III. No patients were staged with ICRS grade IV. Additionally, the scores [except International Knee Documentation Committee (IKDC) at 1 year] of the ICRS grade I group improved more significantly than those of the ICRS grade II and III groups. CONCLUSION: Implantation of hUCB-MSCs with concomitant HTO is an effective treatment for patients with medial compartment osteoarthritis and varus deformity. Regeneration of cartilage improves the clinical outcomes for the patients.

Implantation of allogenic umbilical cord blood-derived mesenchymal stem cells improves knee osteoarthritis outcomes: Two-year follow-up.

INTRODUCTION: Clinical outcomes after the implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in osteoarthritic knees have been rarely reported. Our study aimed to investigate clinical outcomes of osteoarthritic patients who underwent hUCB-MSC implantation. METHODS: In this case series (level of evidence: 4), from January 2014 to December 2015, 128 patients with full-thickness cartilage lesions (International Cartilage Repair Society grade 4 and Kellgren-Lawrence grade ≤3) who underwent hUCB-MSC implantation were retrospectively evaluated with a minimum of 2-year follow-up. After removing the sclerotic subchondral bone with an arthroscopic burr, 4-mm-diameter holes were created at 2-mm intervals, and hyaluronic acid and hUCB-MSCs were subsequently mixed and implanted in the holes and other articular defect sites.Clinical outcomes were evaluated preoperatively, 1 year postoperatively, and 2 years postoperatively (minimum) using visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores. To assess clinical outcomes, patients were divided into two or three groups according to the lesion size, lesion location, number of lesions, body mass index, and age; statistical analyses were performed using these data. RESULTS: The mean (±standard deviation) VAS, WOMAC, and IKDC scores at 1 and 2 years after surgery including hUCB-MSC implantation improved significantly compared to the preoperative scores (P < 0.001). There were significant differences in the lesion location (P < 0.05). Medial femoral condyle lesions resulted in worse outcomes compared with lateral femoral condyle and trochlea lesions. No adverse reactions or postoperative complications were noted. CONCLUSIONS: Implantation of hUCB-MSCs is effective for treating knee osteoarthritis based on a follow-up lasting a minimum of 2 years.

Allogenic umbilical cord blood-derived mesenchymal stem cells implantation for the treatment of juvenile osteochondritis dissecans of the knee.

BACKGROUND: Osteochondritis dissecans (OCD) is a pathologic condition accompanied by the gradual destruction of subchondral bone and defects in the overlying articular cartilage.This case series reports the results of allogenic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation for the treatment of osteochondral defect in two cases of juvenile osteochondritis dissecans. CASE PRESENTATION: Two patients with osteochondral defect of the knee recovered from the disease enough to begin major exercise 1 year after hUCB-MSCs implantation. The IKDC, VAS, and Tegner score of the two patients showed an excellent improvement and concurrent arthroscopy was performed; cartilage regeneration of ICRS grade 1 similar to normal was observed. The modified two-dimensional MOCART scores increased in both cases over time. CONCLUSION: This is the first case series detailing the results of treating juvenile OCD lesions using hUCB-MSCs. This could be an option for treating juvenile OCD.

Cartilage regeneration in osteoarthritic knees treated with distal femoral osteotomy and intra-lesional implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells: A report of two cases.

BACKGROUND: To treat lateral compartment osteoarthritis caused by a valgus deformity, partial or total knee joint arthroplasty is recommended. However, for young patients, joint preservation surgery such as distal femoral osteotomy (DFO) can be an alternative treatment option. Combined cartilage defects of lateral compartment osteoarthritis can be restored by human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). This case report presents the results of DFO and hUCB-MSC implantation for treating two patients with valgus deformity who had lateral compartment osteoarthritis. CASE PRESENTATION: Two middle-aged patients with lateral compartment osteoarthritis and valgus deformity were treated using DFO and hUCB-MSC implantation. They recovered sufficiently to perform moderate exercise one year after surgery. The International Knee Documentation Committee, visual analog scale, and Western Ontario and McMaster Universities Osteoarthritis Index scores showed continuous improvement after surgery. Cartilage regeneration of International Cartilage Repair Society Grade 1, which was similar to normal, was observed in both patients through second-look arthroscopy. With time, the modified two-dimensional magnetic resonance observation of cartilage repair tissue scores also increased in both cases. CONCLUSION: This is the first case report detailing the results of treating lateral compartment osteoarthritis using hUCB-MSCs and DFO. In conclusion, this can be considered a new treatment option for such cases.