Bone Marrow-Derived Cell Therapies to Heal Long-Bone Nonunions: A Systematic Review and Meta-Analysis—Which Is the Best Available Treatment?

Nonunions represent one of the major indications for clinical settings with stem cell-based therapies. The objective of this research was to systematically assess the current evidence for the efficacy of bone marrow-derived cell-based approaches associated or not with bone scaffolds for the treatment of nonunions. We searched MEDLINE (PubMed) and CENTRAL up to July 2019 for clinical studies focused on the use of cell-based therapies and bone marrow derivatives to treat bone nonunions. Three investigators independently extracted the data and appraised the risk of bias. We analysed 27 studies including a total number of 347 participants exposed to four interventions: bone marrow concentrate (BMAC), BMAC combined with scaffold (BMAC/Scaffold), bone marrow-derived mesenchymal stromal cells (BMSCs), and BMSC combined with scaffold (BMSC/Scaffold). Two controlled studies showed a positive trend in bone healing in favour of BMAC/Scaffold or BMSC/Scaffold treatment against bone autograft, although the difference was not statistically significant (RR 0.11, 95% CI -0.05; 0.28). Among single cohort studies, the highest mean pooled proportion of healing rate was reported for BMAC (77%; 95% CI 63%-89%; 107 cases, n=8) and BMAC/Scaffold treatments with (71%; 95% CI 50%-89%; 117 cases, n=8) at 6 months of follow-up. At 12 months of follow-up, an increasing proportion of bone healing was observed in all the treatment groups, ranging from 81% to 100%. These results indicate that BMAC or BMAC/Scaffold might be considered as the primary choice to treat nonunions with a successful healing rate at a midterm follow-up. Moreover, this meta-analysis highlighted that the presence of a scaffold positively influences the healing rate at a long-term follow-up. More case-control studies are still needed to support the clinical improvement of cell-based therapies against autografts, up to now considered as the gold standard for the treatment of nonunions.

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Effects of NSAID use on bone healing: A meta-analysis of retrospective case–control and cohort studies within clinical settings

Trauma ◽

10.1177/1460408619886211 ◽

2019 ◽

Vol 22 (2) ◽

pp. 94-111 ◽

Cited By ~ 1

Author(s):

Muhammad Usman Ali ◽

Mehvish Usman ◽

Kuntal Patel

Keyword(s):

Bone Healing ◽

Meta Analysis ◽

Significant Risk ◽

Case Control ◽

Long Bone ◽

Clinical Settings ◽

Clinical Group ◽

Randomised Trials ◽

Case Control Studies ◽

Retrospective Case

Introduction This meta-analysis aims to determine whether non-steroidal anti-inflammatory drug (NSAID) use is significantly associated with adverse bone healing outcomes within clinical settings, including trauma and elective spine settings. It will also explore bone healing outcomes with the type, route, dosage and duration of NSAID exposure and aims to demonstrate the effects of various other confounding factors on bone healing outcomes. Methods Electronic databases including MedLine, Embase and Cochrane were searched from January 1975 to December 2017. A distinct analysis of observational long bone and spine studies in adult populations was performed, assessing the effects of NSAID exposure on bone healing. Studies from paediatric population and randomised trials also underwent separate assessment in the synthesis. Meta-analysis was conducted in compliance with QUORUM and PRISMA guidelines. Results Quantitative assessment of observational studies suggested a significant risk of bone healing complications with NSAID exposure across each clinical group: long bone (p = 0.0004) and spine (p = 0.02). Analysis of paediatric studies revealed a non-significant association of poor outcomes with NSAID use (p = 0.36), while assessment of randomised trials demonstrated a statistically significant risk of complications following NSAID administration (p = 0.04). Meta-regression further suggested smoking to be a substantial confounder associated with adverse bone healing outcomes (p < 0.00001). Conclusion Inclusion of only fair and moderate-quality retrospective cohort and case–control studies in the current synthesis limits the clinical application of its findings and therefore warrants the need for further research. Thus, attempts to conduct high-quality prospective cohort and randomised trials to study the effects of NSAID use on bone healing would be very helpful and will provide a basis for more extensive research in future.

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Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis

Current Alzheimer Research ◽

10.2174/1567205017666200317102337 ◽

2020 ◽

Vol 17 (2) ◽

pp. 105-111

Author(s):

Haitao Liu ◽

Wei Ge ◽

Wei Chen ◽

Xue Kong ◽

Weiming Jian ◽

...

Keyword(s):

Gene Polymorphism ◽

Large Scale ◽

Late Onset ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Positive Trend ◽

Case Control Studies ◽

China National Knowledge Infrastructure ◽

Aldh2 Gene

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.

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Comparable outcome for autografts and allografts in primary medial patellofemoral ligament reconstruction for patellofemoral instability: systematic review and meta-analysis

Knee Surgery Sports Traumatology Arthroscopy ◽

10.1007/s00167-021-06569-w ◽

2021 ◽

Author(s):

Filippo Migliorini ◽

Andromahi Trivellas ◽

Jörg Eschweiler ◽

Matthias Knobe ◽

Markus Tingart ◽

...

Keyword(s):

Medial Patellofemoral Ligament ◽

Meta Analysis ◽

Patellofemoral Instability ◽

Mpfl Reconstruction ◽

Current Evidence ◽

Level Of Evidence ◽

Feasible Alternative ◽

The Mean ◽

Persistent Instability

Abstract Purpose This study updates the current evidence on the role of allografts versus autografts for medial patellofemoral ligament (MPFL) reconstruction in patients with patellofemoral instability. Methods The study was performed according to the PRISMA guidelines. In March 2021, a literature search in the main online databases was performed. Studies reporting quantitative data concerning primary MPFL reconstruction using an allograft were considered for inclusion. The Coleman Methodology Score was used to assess the methodological quality of the selected articles. Results Data from 12 studies (474 procedures) were retrieved. The mean follow-up was 42.2 (15–78.5) months. The mean age was 21.1 ± 6.2 years. 64.9% (285 of 439) of patients were female. At the last follow-up, the Tegner (p < 0.0001), Kujala (p = 0.002) and the Lysholm (p < 0.0001) scores were minimally greater in the autografts. The similarity was found in the rate of persistent instability sensation and revision. The allograft group evidenced a lower rate of re-dislocations (p = 0.003). Conclusion Allografts may represent a feasible alternative to traditional autograft for MPFL reconstruction in selected patients with patellofemoral instability. Allograft tendons yielded similar PROMs, rates of persistent instability, and revision. Allograft reconstructions tended to have modestly lower re-dislocation rates. Level of evidence IV.

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Effectiveness of e-cigarettes in smoking cessation: a systematic review and meta-analysis

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1226 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

M Oberndorfer ◽

I Grabovac ◽

S Haider ◽

T E Dorner

Keyword(s):

Systematic Review ◽

Smoking Cessation ◽

Meta Analysis ◽

Current Evidence ◽

Promising Alternative ◽

Quality Of Evidence ◽

Different Populations ◽

Meta Analyses

Abstract Background Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to synthesise the current evidence regarding the effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy (NRT) and or counselling) published between 01/01/2014 and 01/05/2019. Data from eligible studies were extracted and used for random-effects meta-analyses. Results Our literature review yielded 13190 publications with 10 studies being identified as eligible for systematic review, covering 8362 participants, and 8 for meta-analyses (n = 30 - 6006). Using the last follow-up of eligible studies, the proportion of smokers achieving abstinence was 1.67 [95CI:0.99 - 2.81] times higher in nicotine EC users compared to non-nicotine EC users. The proportion of abstinent smokers was 1.69 [95CI:1.25 - 2.27] times higher in EC users compared to participants receiving NRT. EC users showed a 2.70 [95CI:1.15 - 6.30] times higher proportion of abstinent smokers in comparison to participants solely receiving counselling. Conclusions Our analysis showed modest effects of nicotine-ECs compared to non-nicotine ECs. When compared to NRT or counselling, results suggest that nicotine EC may be more effective for smoking cessation. As ECs also help maintaining routinized behaviour and social aspects of smoking, we hypothesise that this may explain their advantage as a tool for smoking cessation. However, given the small number of included studies, different populations, heterogeneous designs, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. More comparable data is needed to strengthen confidence in the quality of evidence. Key messages The number of previous studies assessing the effectiveness of ECs for smoking cessation is limited. Further, comparability of these studies is restricted, weakening the quality of evidence. Although current evidence on the effectiveness of ECs for smoking cessation is inconclusive, our meta-analyses suggest that ECs could be a promising alternative tool in attempts to achieve abstinence.

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The Treatment of Acute Diaphyseal Long-bones Fractures with Orthobiologics and Pharmacological Interventions for Bone Healing Enhancement: A Systematic Review of Clinical Evidence

Bioengineering ◽

10.3390/bioengineering7010022 ◽

2020 ◽

Vol 7 (1) ◽

pp. 22

Author(s):

Giuseppe Marongiu ◽

Andrea Contini ◽

Andrea Cozzi Lepri ◽

Matthew Donadu ◽

Marco Verona ◽

...

Keyword(s):

Systematic Review ◽

Growth Factors ◽

Bone Healing ◽

Healing Process ◽

Bone Matrix ◽

Femoral Fractures ◽

Current Evidence ◽

Long Bones ◽

Cell Therapies ◽

Diaphyseal Fractures

Background: The healing of long bones diaphyseal fractures can be often impaired and eventually end into delayed union and non-union. A number of therapeutic strategies have been proposed in combination with surgical treatment in order to enhance the healing process, such as scaffolds, growth factors, cell therapies and systemic pharmacological treatments. Our aim was to investigate the current evidence of bone healing enhancement of acute long bone diaphyseal fractures. Methods: A systematic review was conducted by using Pubmed/MEDLINE; Embase and Ovid databases. The combination of the search terms “long-bones; diaphyseal fracture; bone healing; growth factors; cell therapies; scaffolds; graft; bone substitutes; orthobiologics; teriparatide”. Results: The initial search resulted in 4156 articles of which 37 papers fulfilled the inclusion criteria and were the subject of this review. The studies included 1350 patients (837 males and 513 females) with a mean age of 65.3 years old. Conclusions: General lack of high-quality studies exists on the use of adjuvant strategies for bone healing enhancement in acute shaft fractures. Strong evidence supports the use of bone grafts, while only moderate evidence demineralized bone matrix and synthetic ceramics. Conflicting results partially supported the use of growth factors and cell therapies in acute fractures. Teriparatide showed promising results, particularly for atypical femoral fractures and periprosthetic femoral fractures.

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The impact of smoking on tuberculosis treatment outcomes: a meta-analysis

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0002 ◽

2020 ◽

Vol 24 (2) ◽

pp. 170-175 ◽

Cited By ~ 3

Author(s):

E. Y. Wang ◽

R. A. Arrazola ◽

B. Mathema ◽

I. B. Ahluwalia ◽

S. R. Mase

Keyword(s):

Cigarette Smoking ◽

Treatment Outcomes ◽

Meta Analysis ◽

Current Evidence ◽

Cochrane Library ◽

Loss To Follow Up ◽

Tb Treatment ◽

The Impact ◽

Culture Conversion

BACKGROUND: Cigarette smoking contributes to tuberculosis (TB) epidemiology. However, limited evidence exists on how smoking impacts TB treatment outcomes such as treatment loss to follow-up and culture conversion.METHODS: This meta-analysis assessed current evidence of the impact of active cigarette smoking on TB treatment outcomes. PubMed, Scopus, Embase, and the Cochrane Library were searched for English-language articles published from database inception through 2017. Articles addressing active pulmonary TB and cigarette smoking were identified and data abstracted. Smokers were defined as those who smoked every day or some days at the time of interview/diagnosis. Non-smokers did not smoke at the time of interview/diagnosis. Unfavorable outcomes included any outcome other than cure or completion of TB treatment. Three different data sets were examined: 8 articles addressing unfavorable treatment outcomes, 9 analyzing only treatment loss to follow-up, and 5 addressing delayed smear or culture conversion. Studies that had <20 subjects or that addressed only populations with comorbidities were excluded.RESULTS: We identified 1030 studies; 21 studies fulfilled the inclusion/exclusion criteria. Smokers had greater odds of unfavorable outcomes (pooled odds ratio [pOR] 1.23, 95%CI 1.14–1.33), delayed smear or culture conversion (pOR 1.55, 95%CI 1.04–2.07), and treatment loss to follow-up (pOR 1.35, 95%CI 1.21–1.50).CONCLUSION: Cigarette smoking is associated with negative treatment results and delayed conversion to negative smear or culture, suggesting smoking is an important factor for consideration in TB elimination efforts.

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Association Between Chiropractic Use and Opioid Receipt Among Patients with Spinal Pain: A Systematic Review and Meta-analysis

Pain Medicine ◽

10.1093/pm/pnz219 ◽

2019 ◽

Author(s):

Kelsey L Corcoran ◽

Lori A Bastian ◽

Craig G Gunderson ◽

Catherine Steffens ◽

Alexandria Brackett ◽

...

Keyword(s):

Systematic Review ◽

Confidence Interval ◽

Odds Ratio ◽

Meta Analysis ◽

Spinal Pain ◽

Chiropractic Care ◽

Current Evidence ◽

Inverse Association ◽

Case Control Studies ◽

Opioid Prescription

Abstract Objective To investigate the current evidence to determine if there is an association between chiropractic use and opioid receipt. Design Systematic review and meta-analysis. Methods The protocol for this review was registered on PROSPERO (CRD42018095128). The MEDLINE, PubMed, EMBASE, AMED, CINAHL, and Web of Science databases were searched for relevant articles from database inception through April 18, 2018. Controlled studies, cohort studies, and case–control studies including adults with noncancer pain were eligible for inclusion. Studies reporting opioid receipt for both subjects who used chiropractic care and nonusers were included. Data extraction and risk of bias assessment were completed independently by pairs of reviewers. Meta-analysis was performed and presented as an odds ratio with 95% confidence interval. Results In all, 874 articles were identified. After detailed selection, 26 articles were reviewed in full, and six met the inclusion criteria. Five studies focused on back pain and one on neck pain. The prevalence of chiropractic care among patients with spinal pain varied between 11.3% and 51.3%. The proportion of patients receiving an opioid prescription was lower for chiropractic users (range = 12.3–57.6%) than nonusers (range = 31.2–65.9%). In a random-effects analysis, chiropractic users had a 64% lower odds of receiving an opioid prescription than nonusers (odds ratio = 0.36, 95% confidence interval = 0.30–0.43, P < 0.001, I2 = 92.8%). Conclusions This review demonstrated an inverse association between chiropractic use and opioid receipt among patients with spinal pain. Further research is warranted to assess this association and the implications it may have for case management strategies to decrease opioid use.

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Association between Estrogen Receptor-αGene XbaI and PvuII Polymorphisms and Periodontitis Susceptibility: A Meta-Analysis

Disease Markers ◽

10.1155/2015/741972 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Hong Weng ◽

Chao Zhang ◽

Yuan-Yuan Hu ◽

Rui-Xia Yuan ◽

Hong-Xia Zuo ◽

...

Keyword(s):

Estrogen Receptor ◽

Chronic Periodontitis ◽

Meta Analysis ◽

Current Evidence ◽

Case Control Studies ◽

Chinese Han ◽

Female Population ◽

Increased Risk ◽

Pvuii Polymorphism ◽

Xbai Polymorphism

Background. Certain studies have previously explored the association between the estrogen receptor-α(ER-α) gene polymorphisms and periodontitis susceptibility, although the current results are controversial. The present study, using meta-analysis, aimed to investigate the nature of the genetic susceptibility of the ER-αfor developing periodontitis.Methods. A comprehensive literature search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to January 8, 2015. Statistical manipulation was performed using Stata version 13.0 software. Odds ratios (ORs) and corresponding 95% confident intervals (CIs) were calculated to estimate the association in five genetic models.Results. A total of 17 eligible case-control studies from seven identified publications consisting of nine studies for the XbaI polymorphism and eight studies for the PvuII polymorphism were included in the meta-analysis. We found elevated risk of periodontitis in XbaI XX genotype carriers. Moreover, subgroup analyses demonstrated increased risk for chronic periodontitis of XbaI XX genotype carriers, specifically in the Chinese Han female population. No significant association was observed between PvuII polymorphism and periodontitis.Conclusion. Current evidence indicated that the homozygote (XX) genotype of ER-αgene XbaI polymorphism, but not PvuII mutation, may increase the risk of chronic periodontitis, specifically in the Chinese Han female population.

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Impact of XPF rs2276466 polymorphism on cancer susceptibility: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20181785 ◽

2019 ◽

Vol 39 (5) ◽

Author(s):

Yezhou Liu ◽

Kun Liu ◽

Xueru Zhao ◽

Yidan Sun ◽

Ning Ma ◽

...

Keyword(s):

Cancer Risk ◽

Gastrointestinal Cancer ◽

Cancer Susceptibility ◽

Excision Repair ◽

Meta Analysis ◽

Complementation Group ◽

Current Evidence ◽

Case Control Studies ◽

Summary Estimate ◽

The Impact

Abstract Association between the xeroderma pigmentosum complementation group F (XPF)rs2276466 located in the excision repair cross complementation group 4 (ERCC4) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. PubMed, Embase and Science-Web databases were searched systematically up to May 20, 2018, to obtain all the records evaluating the association between the rs2276466 polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as a measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on gastrointestinal cancer, neurogenic cancer and other cancers (breast cancer and SCCHN). All the analyses were carried out in STATA 14.1.11 case–control studies that consisted of 5730 cases and 6756 controls, were eventually included in our meta-analysis. The significant association was observed between the XPFrs2276466 polymorphism and neurogenic cancer susceptibility (recessive model: OR = 1.648, 95% CI = 1.294–2.098, P<0.001). Furthermore, no significant impact of this polymorphism was detected on decreased gastrointestinal cancer risk (dominant model: OR = 1.064, 95%CI = 0.961–1.177, P = 0.233). The rs2276466 polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with gastrointestinal susceptibility. However, this polymorphism might contribute to increased neurogenic cancer risk. More preclinical and epidemiological studies are still imperative for further evaluation

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Autologous bone-marrow mononuclear stem cell therapy in patients with stroke: a meta-analysis of comparative studies

BioMedical Engineering OnLine ◽

10.1186/s12938-020-00819-7 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Sorayouth Chumnanvej ◽

Siriluk Chumnanvej

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Bone Marrow Mononuclear Cell ◽

Stroke Patients ◽

Stroke Treatment

Abstract Background There is a need to promote recovery after stroke with novel therapeutic interventions. Of them, bone-marrow mononuclear cell (BM-MNC) therapy offers promising outcomes in preclinical and clinical models. Aims To investigate the efficacy and safety of BM-MNCs versus traditional medical care of stroke patients. Summary of review A meta-analysis was conducted involving controlled prospective studies and randomized clinical trials (RCTs) which investigated the changes in the scores of neurological functions (the National Institutes of Health Stroke Scale [NIHSS]), the indices of functional recovery (the Barthel Index [BI] and the modified Rankin scale [mRS]) at 3 and 6 month post-transplantation. A total of nine studies (five RCTs) recruited 469 stroke patients (65.5% males, 49.25% received the intervention). There were no significant differences in NIHSS, BI, or mRS scores after 3 months of follow-up. However, the BI indices of BM-MNCs-receiving patients improved significantly after 6 months (standardized mean difference = 1.17, 95% confidence interval, 0.23 to 2.10, P = 0.01) as compared to traditional treatment. The risk of mortality and adverse events and the proportion of patients with favorable outcomes (mRS ≤ 3) were similar in both groups. Conclusion Both the BM-MNCs and medical stroke treatment have similar outcomes in terms of safety and short-term efficacy, while the effect of therapy is significant only after 6 months. More well-designed, large sized RCTs are needed to confirm the efficacy of stem cell therapy over long periods of follow-up.

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