Meta-analysis of clinical trials focusing on hypertonic dextrose prolotherapy (HDP) for knee osteoarthritis.

Hypertonic dextrose prolotherapy (HDP) is an injection of a concentrated dextrose solution for the purpose of local treatment of musculoskeletal pain and possible enhancement of repair mechanisms. This systematic review and meta-analysis examines the clinical utility of HDP injection for treatment of knee osteoarthritis (OA). Randomized controlled trials (RCTs) utilizing HDP to treat knee OA were retrieved from MEDLINE, EMBASE, and Cochrane Library (CENTRAL). Identification and inclusion of RCTs utilizing intra-articular and extra-articular administration of HDP vs administration of other injectate or physical therapy as control for knee OA were included. Primary clinical outcomes were changes in knee WOMAC, pain and function score. Secondary outcomes were adverse events related to HDP. For continuous outcomes with same or different measurements, we calculated, respectively the weighted mean difference (WMD) or the standardized mean difference (SMD), respectively. Results were pooled using DerSimonian and Laird random effect models across the included studies and heterogeneity between studies was estimated using the I2 index. Five studies comprising a total of 319 treated patients met inclusion criteria and were included in the final analysis. At a mean of 22.8 weeks follow-up, HDP treatment significantly improved total WOMAC score (WMD = 13.77, 95% CI: 6.75-20.78; p < 0.001; I2 = 90%), pain (SMD = 1.33, 95% CI: 0.49-2.17; p < 0.001; I2 = 91%) and knee function (SMD = 1.30, 95% CI: 0.45-2.14; p < 0.001; I2 = 91%) compared with control group. There were no severe adverse events related to dextrose injection reported in all the included studies. HDP is a promising treatment for knee OA with a reasonable safety profile. Further research in mechanism of HDP activity and long-term follow-up study will be needed for exploring this novel therapy modality.

Clinical effectiveness of ultrasound guided subacromial-subdeltoid bursa injection of botulinum toxin type A in hemiplegic shoulder pain: A retrospective cohort study.

Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, n = 18; corticosteroid group, n = 20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, P < .05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, P > .05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, P > .05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.

Cell-Based Therapies for Lumbar Discogenic Low Back Pain: Systematic Review and Single-Arm Meta-analysis.

STUDY DESIGN: A systematic review and single-arm meta-analysis of clinical trials. OBJECTIVE: To assess the efficacy of mesenchymal stem cells or chondrocyte in patients with discogenic low back pain. SUMMARY OF BACKGROUND DATA: There is no previous review evaluated the efficacy of mesenchymal stem cell or chondrocyte therapy in adults with discogenic low back pain. METHODS: A comprehensive literature search was conducted on PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO, and Web of Science from database inception through on September 10th, 2015. We included clinical trials that evaluated stem cells or chondrocyte-based therapy in patients with discogenic back pain. The primary outcomes of interest were pain score and Oswestry Disability Index (ODI). We performed random-effects model meta-analyses to assess net changes in the same outcome variables. Heterogeneity between studies was estimated by I statistic. RESULTS: The initial search identified 1393 articles, of which 6 studies were eligible for this review. The pooled mean difference in pain score from baseline to follow-up points was 44.2 points decreased (95% CI: -61.8 to -26.5, P < 0.001, I  = 99.4%). Meanwhile, the pooled mean difference in ODI from baseline to follow-up points was 32.2 points decreased (95% CI: -41.6 to -22.9, P < 0.001, I  = 99.5%). No related adverse effects were reported by the included studies. CONCLUSION: Cell-based therapy is for patients who have discogenic low back pain associated with improved pain relief and ODI. More stringently designed randomized double-blind clinical trials with appropriately determined sample sizes will be needed to confirm its clinical efficacy and safety. LEVEL OF EVIDENCE: 4.

Intra-articular injections of botulinum toxin a for refractory joint pain: a systematic review and meta-analysis.

OBJECTIVE: To assess the benefit of intra-articular injection of Botulinum toxin A (BoNT-A) for chronic refractory joint pain regardless of joint or pathology. DATA SOURCES: The search was performed on Ovid MEDLINE(R) In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R), Ovid EMBASE, Web of Science, and Scopus inception through Week 12, 2016. Trial selection: Clinical randomized controlled trials that evaluated BoNT-A intra-articular injection in patients with refractory joint pain were included. DATA EXTRACTION: Two independent reviewers conducted data extraction. RESULTS: A total of 6 out of 284 records were included. The analysis indicated that a statistically significant decreased pain score was found in BoNT-A therapy group than control group with WMD=1.10 (95% CI: 0.35 to 1.85; P<0.001; I2=95%); WMD=0.7 (95% CI: 0.09 to 1.32; P=0.02; I2=0%) at week 4, and 8 after injection, respectively. WOMAC score was also significant decreased in BoNT-A therapy group than control group with WMD=4.71 (95% CI: 2.76 to 6.67; P<0.001; I2=0%); WMD=3.67 (95% CI: 1.08 to 6.26; P=0.006; I2=27%) at week 4 and12 after injection, respectively. There was no difference in adverse event between BoNT-A therapy group and control group with OR=1.25 (95% CI: 0.88 to 1.78; P=0.47; I2=0%). CONCLUSION: As compared with conventional therapy, BoNT-A intra-articular injection have beneficial effects with improved pain score and WOMAC score in adult patients with refractory joint pain.

Effectiveness of Botulinum Toxin for Lower Limbs Spasticity after Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate current evidence of the effectiveness of botulinum toxin (BTX) injection for lower limbs spasticity after stroke. METHODS: Ovid MEDLINE(R) In-Process and Other Non-Indexed Citations，Ovid MEDLINE(R), Ovid EMBASE, Web of Science, and PubMed (NLM) from database were searched inception through Week 23, 2015. Randomized controlled trials (RCTs) comparing the clinical efficacy of BTX injection to placebo or conventional therapy on lower limbs spasticity after stroke were included. We constructed random effects models and calculated mean difference (MD) or standardized mean difference (SMD) for continuous outcomes. RESULTS: One thousand three hundred and forty-three records were identified and among them 7 articles (603 patients) were eligible for the final analysis. A statistically significant decrease in muscle tone was observed at week 4 and 12 after injection (Subgroup analysis, SMD = 0.85, 95% CI: 0.2-1.5; p = 0.001; I(2) = 81% and SMD = 0.42, 95% CI: 0.07-0.77; p = 0.02; I(2) = 45%, respectively). Patients who received in BTX therapy were likely to have significant increased Fugl-Meyer score than control group with MD = 3.19 (95% CI: 0.22-6.16, p = 0.04, I(2) = 96%). There was no difference in gait speed between two groups during whole follow-up period. CONCLUSION: BTX showed more persistent clinical benefits in lower limbs spasticity and Fugl-Meyer score than placebo in patients after stroke. These results suggest that BTX could be a useful and safety strategy for the treatment of lower limbs spasticity after stroke. Further investigation is required to determine the effectiveness of BTX injection for stroke patients with optimal timing and dose of intervention.

Ultrasound-guided versus landmark in knee arthrocentesis: A systematic review.

OBJECTIVES: The objective was to assess the efficacy of ultrasound-guided (USG) versus landmark (LM) knee arthrocentesis in adults with knee pain or effusion. METHODS: A systematic review of the literature was performed until August 2015. All controlled trials reporting the accuracy or clinical efficacy between USG and LM knee joint arthrocentesis were selected. Pooled weighted mean difference (WMD) using the D-L fixed models for continuous outcomes and the risk ratio (RR) for dichotomous outcomes were assessed by meta-analysis. Heterogeneity between studies was estimated by I(2) statistic. RESULTS: Nine studies including 715 adult patients (725 knee joints) were eligible for this review versus LM group; there was a statistically significant difference in favor of USG for knee arthrocentesis accuracy rate (risk ratio = 1.21; 95% CI: 1.13-1.29; P < 0.001; I(2) = 37%), lower procedural pain scores (WMD = -2.24; 95% CI: -2.92 to -1.56; P < 0.001; I(2) = 4%), more aspiration volume (WMD = 17.06; 95% CI: 5.98-28.13; P = 0.003; I(2) = 57%), and decreased pain score 2 weeks after injection (WMD = 0.84; 95% CI: 0.42-1.27; P < 0.001; I(2) = 0). There was no statistically significant difference in procedural duration between two groups (WMD = -0.8; 95% CI: -2.24 to 0.74; P = 0.31; I(2) = 0). CONCLUSIONS: Ultrasound-guided knee joint arthrocentesis offer a significantly greater accuracy and clinical improvement over landmark technique in adults with knee pain or joint effusion.

Effectiveness of Ultrasound-Guided Versus Fluoroscopy or Computed Tomography Scanning Guidance in Lumbar Facet Joint Injections in Adults With Facet Joint Syndrome: A Meta-Analysis of Controlled Trials.

OBJECTIVE: To review the literature and assess the comparative effectiveness of ultrasound-guided (USG) versus computed tomography (CT)-/fluoroscopy-guided lumbar facet joint injections in adults. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid Embase, EBSCO, and Web of Science. STUDY SELECTION: Randomized or nonrandomized controlled trials comparing the clinical effectiveness between USG and CT-/fluoroscopy-guided injection techniques in patients with facet syndrome were included. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts. The results of the mean procedure duration, decreased pain score, and Modified Oswestry Disability score after treatment were extracted and presented in the form of mean ± SD. DATA SYNTHESIS: There were 103 records screened; 3 studies were included, with a total of 202 adults with facet joint pain. There was no statistically significant difference between the 2 groups in pain score and Modified Oswestry Disability score after injection (weighted mean difference [WMD], .07; 95% confidence interval [CI], -.51 to .65; P=.80; I(2)=78%; WMD, -.55; 95% CI, -1.31 to .22; P=.16; I(2)=0%, respectively). There was also no statistically significant difference in the mean procedure duration between the 2 groups (standardized mean difference [SMD], .97; 95% CI, -1.01 to 2.94; P=.34; I(2)=97%). CONCLUSIONS: This review suggested that no significant differences in pain and functional improvement were noted between the USG and CT-/fluoroscopy-guided techniques in facet joint injection. USG injection is feasible and minimizes exposure of radiation to patients and practitioners in the lumbar facet joint injection process.

Ultrasound-guided versus blind subacromial-subdeltoid bursa injection in adults with shoulder pain: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness of ultrasound-guided (USG) versus blind (landmark-guided, LMG) corticosteroid subacromial-subdeltoid bursa injection in adults with shoulder pain. METHODS: The searches were performed on PubMed, Ovid MEDLINE, Ovid EMBASE, Ovid CochraneCENTRAL, Web of Science, Google Scholar, and Scopus from database inception through March 27, 2015. Studies were included trials comparing USG versus LSG injections for the treatment of adults with subacromial-subdeltoid bursitis. Two reviewers independently performed data extraction and appraisal of the studies. The outcome measures collected were the decreased VAS and SDQ scores, the increased shoulder function scores and shoulder abduction motion range, and the effective rate at 6 weeks after injection. RESULTS: Seven papers including 445 patients were reviewed; 224 received LMG injections and 221 received USG injections. There was a statistically significant difference in favor of USG for pain score [MD = 1.19, 95% CI (0.39, 1.98), P = 0.003] and SDQ score [MD = 5.01, 95% CI (1.82, 8.19), P = 0.02] at 6 weeks after injection. Also there was a statistically significant difference between the groups, with greater improvement reported of shoulder function scores [SMD = 0.89, 95% CI (0.56, 1.23), P < 0.001] and shoulder abduction motion range [MD 32.69, 95% CI (14.82, 50.56), P < 0.001] in the USG group. More effective rate was also reported with USG group and the difference was statistically significant [risk ratio = 1.6, 95% CI (1.02, 2.50), P = 0.04]. CONCLUSIONS: Ultrasound-guided corticosteroid injections potentially offer a significantly greater clinical improvement over blind SASD bursitis injections in adults with shoulder pain.

Effectiveness of Botulinum Toxin for Shoulder Pain Treatment: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the current evidence of the effectiveness of botulinum toxin (BTX) treatment for shoulder pain. DATA SOURCES: Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus were searched from inception through week 18 of 2015. STUDY SELECTION: Randomized controlled trials comparing the clinical efficacy (pain intensity and shoulder range of motion [ROM]) of BTX injection to conventional therapy (steroid or placebo injection) were included. DATA EXTRACTION: Two reviewers independently screened abstracts and full texts. The results of the pain intensity and shoulder ROM were extracted and presented in the form of mean and SD. We constructed random-effects models and calculated the mean difference (MD) for continuous outcomes. A total of 219 articles were identified, of which 9 articles were eligible for the final analysis. DATA SYNTHESIS: The analysis indicated a statistically significant decreased pain score in the BTX therapy group compared with the control group, with the MD=1.35 (95% confidence interval [CI], .80-1.91; P<.001; I(2)=81%). Patients who received BTX therapy were more likely to have a significant increase in shoulder abduction ROM than patients in the control group, with the MD=8.02 (95% CI, 1.17-14.88, P=.02, I(2)=89%). CONCLUSIONS: Compared with conventional (steroid or placebo injection) therapy, BTX injections have beneficial effects for adult patients with shoulder pain, evidenced by improved pain scores and ROM.

Electrospun scaffolds for multiple tissues regeneration in vivo through topography dependent induction of lineage specific differentiation.

Physical topographic cues from various substrata have been shown to exert profound effects on the growth and differentiation of stem cells due to their niche-mimicking features. However, the biological function of different topographic materials utilized as bio-scaffolds in vivo have not been rigorously characterized. This study investigated the divergent differentiation pathways of mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group was observed to form more mature tendon-like tissue in the Achilles tendon injury model, as evidenced by histological scoring and collagen I immunohistochemical staining data. In contrast, the randomly-oriented group exhibited much chondrogenesis and subsequent bone tissue formation through ossification. Additionally, X-ray imaging and osteocalcin immunohistochemical staining also demonstrated that osteogenesis in vivo is driven by randomly oriented topography. Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and enhanced tenogenic differentiation compared to cells grown on randomly-oriented scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber scaffolds displayed enhanced osteogenic differentiation compared with cells cultured on aligned fiber scaffolds. Finally, it was demonstrated that cytoskeletal tension release abrogated the divergent differentiation pathways on different substrate topography. Collectively, these findings illustrate the relationship between topographic cues of the scaffold and their inductive role in tissue regeneration; thus providing an insight into future development of smart functionalized bio-scaffold design and its application in tissue engineering.

The effect of decellularized matrices on human tendon stem/progenitor cell differentiation and tendon repair.

It is reported that decellularized collagen matrices derived from dermal skin and bone have been clinically used for tendon repair. However, the varying biological and physical properties of matrices originating from different tissues may influence the differentiation of tendon stem cells, which has not been systematically evaluated. In this study, the effects of collagenous matrices derived from different tissues (tendon, bone and dermis) on the cell differentiation of human tendon stem/progenitor cells (hTSPCs) were investigated, in the context of tendon repair. It was found that all three matrices supported the adhesion and proliferation of hTSPCs despite differences in topography. Interestingly, tendon-derived decellularized matrix promoted the tendinous phenotype in hTSPCs and inhibited their osteogenesis, even under osteogenic induction conditions, through modulation of the teno- and osteolineage-specific transcription factors Scleraxis and Runx2. Bone-derived decellularized matrix robustly induced osteogenic differentiation of hTSPCs, whereas dermal skin-derived collagen matrix had no apparent effect on hTSPC differentiation. Based on the specific biological function of the tendon-derived decellularized matrix, a tissue-engineered tendon comprising TSPCs and tendon-derived matrix was successfully fabricated for Achilles tendon reconstruction. Implantation of this cell-scaffold construct led to a more mature structure (histology score: 4.08 ± 0.61 vs. 8.51 ± 1.66), larger collagen fibrils (52.2 ± 1.6 nm vs. 47.5 ± 2.8 nm) and stronger mechanical properties (stiffness: 21.68 ± 7.1 Nm m(-1) vs.13.2 ± 5.9 Nm m(-1)) of repaired tendons compared to the control group. The results suggest that stem cells promote the rate of repair of Achilles tendon in the presence of a tendinous matrix. This study thus highlights the potential of decellularized matrix for future tissue engineering applications, as well as developing a practical strategy for functional tendon regeneration by utilizing TSPCs combined with tendon-derived decellularized matrix.