Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review

SummaryBackgroundAn important goal of stem cell research in orthopaedics is to develop clinically relevant techniques that could be applied to heal cartilage or joint pathology. Stem cell treatment in orthopaedics for joint pathology is promising since these cells have the ability to modulate different processes in the various tissues of the joint simultaneously. The non life-threatening nature of musculoskeletal system disorders makes safety of stem cell therapy a necessary prerequisite.ObjectiveTo systematically review the literature and provide an overview of reported adverse events (AEs) of intra-articular treatment with culture-expanded stem cells in humans.DesignA systematic literature search was performed in Pubmed, EMBASE, Web of Science and CINAHL in February 2013. AEs were reported into three categories: local/systemic, serious adverse event or AE (SAE/AE), related/unrelated.Results3039 Potentially eligible articles were identified of which eventually eight fulfilled our inclusion criteria. In total, 844 procedures with a mean follow-up of 21 months were analysed. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) were used for cartilage repair and osteoarthritis treatment in all included studies. Four SAEs were reported by the authors. One infection following bone marrow aspiration (BMA) was reported as probably related and resolved with antibiotics. One pulmonary embolism occurred 2 weeks after BMA and was reported as possibly related. Two tumours, both not at the site of injection, were reported as unrelated. Twenty-two other cases of possible procedure-related and seven of possible stem cell-product related adverse events (AEs) were documented. The main AEs related to the procedure were increased pain/swelling and dehydration after BMA. Increased pain and swelling was the only AE reported as related to the stem cell-product.ConclusionsBased on current literature review we conclude that application of cultured stem cells in joints appears to be safe. We believe that with continuous caution for potential side effects, it is reasonable to continue with the development of articular stem cell therapies

Foot orthoses for flexible flatfeet in children and adults: a systematic review and meta-analysis of patient-reported outcomes

Background This systematic review and meta-analysis examined the effectiveness of orthoses for flexible flatfeet in terms of patient-reported outcomes in children and adults. Methods EMBASE, Medline (OvidSP), Web-of-Science, Scopus, CINAHL, Cochrane Central Register of Controlled Clinical Trials, i.e., Cochrane Central and Pubmed were searched to identify relevant studies since their inception up to February 2021. We included randomized controlled trials (RCT) and prospective studies in which patient reported outcomes at baseline and follow-up in an orthoses group were compared with a no orthoses or sham sole group. Methodological quality of the studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). A meta-analysis was performed where there were multiple studies with the same outcome measures, which was the case for the Visual Analogue Scale (VAS) for pain in adults. Results In total nine studies were included: four RCT in children (N = 353) and four RCT and one prospective study in adults (N = 268) were included. There was considerable heterogeneity between studies. A meta-analysis demonstrated that pain reduction between baseline and follow-up was significantly larger in the orthoses (N = 167) than in the control groups in adults (N = 157; - 4.76, 95% CI [- 9.46, - 0.06], p0.05). Conclusion Due to heterogeneity in study designs, we cannot conclude that foot orthoses are useful for flexible flatfoot in children and adults. However, based on the meta-analysis orthoses might be useful in decreasing pain in adults. The authors did not receive support from any organization for the submitted work

Quality of life after hip fracture in the elderly: A systematic literature review

Background With an increasing ageing population, hip fractures have become a major public health issue in the elderly. It is important to examine the health status (HS) and health-related quality of life (HRQOL) of the elderly faced with the epidemic of hip fractures. Objective To provide an overview of reported HS and HRQOL in elderly patients with a hip fracture. Design A systematic literature search was performed in Embase, Medline, Web of Science, Scopus, CINAHL, Cochrane, PsycINFO, Pubmed, and Google Scholar in July 2014. Studies which reported the HS or HRQOL based on standardised questionnaires in patients older than 65 years with a hip fracture were considered eligible for inclusion. Results After inspecting the 2725 potentially eligible studies, 49 fulfilled the inclusion criteria. All included studies were randomised controlled trials or prospective cohort studies. The methodological quality of the studies was moderate. Patients’ functioning on the physical, social, and emotional domains were affected after a hip fracture. The HS and HRQOL of the majority of patients recovered in the first 6 months after fracture. However, their HS did not return to prefracture level. Mental state, prefracture functioning on physical and psychosocial domains, comorbidity, female gender, nutritional status, postoperative pain, length of hospital stay, and complications were factors associated with HS or HRQOL. Treatment with total hip arthroplasty or hemi-arthroplasty provided better HS than treatment with internal fixation with displaced femoral neck fractures. Supportive psychotherapy in “low-functioning” patients, (home) rehabilitation programmes and nutritional supplementation appeared to have beneficial effects on HS. Conclusions Optimizing nutrition intake, (home) rehabilitation programmes, and the possibility for psychological counselling in patients with difficulties in the psychosocial dimensions would be recommended after hip fracture surgery. Besides HS questionnaires like EQ-5D and SF-36, adequate measurements like the WHOQOL-Bref or ICECAP-O are warranted in future studies regarding hip fracture surgery and postoperative treatment options. Keywords Hip fracture Health-related quality of life, Health status, Elderly, Systematic revie