Is there sufficient evidence to support the use of antibiotic holiday just before the second stage of an infected total hip or knee arthroplasty revision surgery?

The practice of implementing an antibiotic holiday before the second stage of hip or knee arthroplasty is currently controversial due to limited evidence for this approach, as per the International Consensus Meeting 2018 on Musculoskeletal Infection. A greater understanding of this issue could augment the quality of Alrayes and Sukeik's mini-review (2023) on diagnosing, managing, and treating periprosthetic knee infections. However, a significant lack of literature exists concerning the optimal duration for the antibiotic holiday, calling for more research before establishing any clinical guidelines.

A Novel Surgical Treatment Management Algorithm for Elbow Posterolateral Rotatory Instability (PLRI) Based on the Common Extensor Origin Integrity.

Background: Here, we introduce a comprehensive treatment algorithm for posterolateral rotatory instability (PLRI) of the elbow, a condition affecting elbow mobility. We outline a diagnostic approach and a novel surgical management plan through the arthroscopic surgeon's point of view. Methods: The central focus of this management approach is the integrity of common extensor origin (CEO). High clinical suspicion must be evident to diagnose PLRI. Special clinical and imaging tests can confirm PLRI but sometimes the final confirmation is established during the arthroscopic treatment. The most appropriate treatment is determined by the degree of CEO integrity. Results: The treatment strategy varies with the CEO's condition: intact or minor tears require arthroscopic lateral collateral ligament imbrication, while extensive tears may need plication reinforced with imbrication or, in cases of retraction, a triceps tendon autograft reconstruction of the lateral ulnar collateral ligament alongside CEO repair. These approaches aim to manage residual instability and are complemented using a tailored rehabilitation protocol to optimize functional outcomes. Conclusion: PLRI is a unique clinical condition and should be treated likewise. This algorithm offers valuable insights for diagnosing and treating PLRI, enhancing therapeutic decision-making.

Deap-seated infection and nonunion following internal fixation for Charcot foot deformity correction. A proportional meta-analysis of level 4 evidence.

BACKGROUND: Given the paucity of literature on the management of infected metalwork and nonunion in neuropathic diabetic patients, a meta-analysis was designed to investigate the two major complications following Charcot reconstruction performed by means of internal fixation methods. METHODS: We searched PubMed, Scopus and CENTRAL until the 17th of May 2022 for completed studies investigating outcomes following midfoot and/or hindfoot and/or ankle diabetic Charcot reconstruction. For a paper to qualify for inclusion, an internal fixation element should have been considered. Random effects meta-analysis of proportion was performed to calculate the rate of post-operative deep-seated infections with the associated amputation rate and nonunions by using Open Meta-analyst software. Sub-analysis linked to anatomical location of reconstruction was performed and the quality of the included studies was appraised using the Moga tool. RESULTS: Thirty studies with 492 eligible reconstructions were considered. Of those, deep-seated infections were diagnosed in 46 cases (Estimated proportion was 6.7%, 95% CI [4.2%-9.2%]). Debridement and antibiotic administration with or without metalwork removal were considered in the majority of the participants with successful clinical outcomes. Amputation was performed in 15 patients due to unmanageable post-operative infection and nonunion was reported in 17 studies (Estimated rates were 36.6%, 95% CI [18.4%-56.3%]; and 11.9%, 95%CI [6.6%-18.1%]; respectively). CONCLUSIONS: Meta-analysis showed that although the overall risk of infection development is less than 10%, just below one third of the infected cases undergo late amputation. Moreover, internal fixation reconstructions carry a nonunion risk of just above 10%.

Septic Tibial Nonunions on Proximal and Distal Metaphysis-A Systematic Narrative Review.

BACKGROUND: Infected nonunion of the tibia represents a challenging complication for orthopedic surgeons and poses a major financial burden to healthcare systems. The situation is even more compounded when the nonunion involves the metaphyseal region of long bones, a rare yet demanding complication due to the poor healing potential of infected cancellous bone; this is in addition to the increased likelihood of contamination of adjacent joints. The purpose of this study was to determine the extent and level of evidence in relation to (1) available treatment options for the management of septic tibial metaphyseal nonunions; (2) success rates and bone healing following treatment application; and (3) functional results after intervention. METHODS: We searched the MEDLINE, Embase, and CENTRAL databases for prospective and retrospective studies through to 25 January 2021. Human-only studies exploring the efficacy of various treatment options and their results in the setting of septic, quiescent, and metaphyseal (distal or proximal) tibia nonunions in the adult population were included. For infection diagnosis, we accepted definitions provided by the authors of source studies. Of note, clinical heterogeneity rendered data pooling inappropriate. RESULTS: In terms of the species implicated in septic tibial nonunions, staphylococcus aureus was found to be the most commonly isolated microorganism. Many authors implemented the Ilizarov external fixation device with a mean duration of treatment greater than one year. Exceptional or good bone and functional results were recorded in over 80% of patients, although the literature is scarce and possible losses of the follow-up were not recorded. CONCLUSION: A demanding orthopedic condition that is scarcely studied is infected metaphyseal tibial nonunion. External fixation seems promising, but further research is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO No. CRD42020205781.

Treatment of Infected Tibial Metaphyseal Nonunions Using the Ilizarov Method: Protocol for a Prospective Nonrandomized Study.

BACKGROUND: The management of infected metaphyseal nonunion of the tibia is devastating, especially when associated with significant bone loss, poor soft tissues, draining sinuses, axial deformity, knee or ankle joint stiffness, limb discrepancy, and multiresisted pathogens. A systematic review, performed recently by the primary investigators but not yet published, yielded the lack of studies in the field and the huge heterogeneity of the presented results. We found several bias and controversies such as no clear definition of the exact part of the tibia where the nonunion was located, the pathogen causing the fracture-related infection, the number of previous interventions and time to presentation, and the exact type of treatment methods including the use of muscle flaps or bone grafting. Time to final union as a functional score is another important but missing data. OBJECTIVE: The proposed study is designed to evaluate a sufficient number of patients with infected metaphyseal tibial nonunions using various general health, functional, and bone scores. METHODS: This prospective clinical trial study, with a minimum follow-up period of 36 months, focuses on the effectiveness of the Ilizarov method after radical nonunion debridement and targeted antibiotic therapy in patients with infected metaphyseal tibial nonunions. The primary outcomes would be the definite healing of nonunion and infection-free results. Secondary outcomes would be limb alignment and discrepancy, alteration in the patient's quality of life, and functional results. A power analysis calculated a minimum of 11 patients to obtain statistical power, but we aim to include at least 25 patients. Limb discrepancy, clinical validation of infection eradication and fracture healing, radiographic validation, and patient-reported outcome measures will be highlighted and correlated. Statistical analysis of the results will offer data missing from the literature so far. Measurements are scheduled at specific times for each patient: preoperatively, 3 and 6 months postoperatively, 1 month after Ilizarov frame removal, and once per semester afterward until the end of the follow-up period (minimum 36 months). Laboratory evaluation will be assessed once per month. Any complication will be reported and treated when it occurs. RESULTS: The trial has already started. It was funded in June 2020. As of May 2022, 19 participants have been recruited and no major complications have been noticed yet. Data analysis will be performed after data collection ends, and results will be published afterward. CONCLUSIONS: An infected metaphyseal tibial nonunion is a rare condition with limited treatment options and many controversies. There is no consensus in the literature about the best treatment strategy, and this lack of evidence should be fulfilled. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 30905788; https://www.isrctn.com/ISRCTN30905788. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39319.

Viral infections in orthopedics: A systematic review and classification proposal.

BACKGROUND: Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might have been underestimated. AIM: To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the Reference Citation Analysis (RCA), and Scopus for completed studies published before January 30, 2021, to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies, Moga score for case series, Wylde score for registry studies, and Newcastle-Ottawa Scale for case-control studies. RESULTS: Six human and four animal studies were eligible for inclusion in the qualitative synthesis. Hepatitis C virus was implicated in several peri- and post-operative complications in patients without cirrhosis after major orthopedic surgery. Herpes virus may affect the integrity of lumbar discs, whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss. CONCLUSION: Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis. Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms. Therefore, based on our literature search, the proposed clinical and pathogenetic classification scheme is as follows: (1) Viral infections of bone or joint; (2) Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues; and (3) Viral infection as a risk factor for post-surgical bacterial infection.

Comment on Oldrini et al. PHILOS Synthesis for Proximal Humerus Fractures Has High Complications and Reintervention Rates: A Systematic Review and Meta-Analysis. Life 2022, 12, 311.

We read the paper published by Oldrini, L.M. et al. (2022) [...].

Network meta-analyses: Methodological prerequisites and clinical usefulness.

It is an undeniable fact that systematic reviews play a crucial role in informing clinical practice; however, conventional head-to-head meta-analyses do have limitations. In particular, studies can only be compared in a pair-wise fashion, and conclusions can only be drawn in the light of direct evidence. In contrast, network meta-analyses can not only compare multiple interventions but also utilize indirect evidence which increases their precision. On top of that, they can also rank competing interventions. In this mini-review, we have aimed to elaborate on the principles and techniques governing network meta-analyses to achieve a methodologically sound synthesis, thus enabling safe conclusions to be drawn in clinical practice. We have emphasized the prerequisites of a well-conducted Network Meta-Analysis (NMA), the value of selecting appropriate outcomes according to guidelines for transparent reporting, and the clarity achieved via sophisticated graphical tools. What is more, we have addressed the importance of incorporating the level of evidence into the results and interpreting the findings according to validated appraisal systems (i.e., the Grade of Recommendations, Assessment, Development, and Evaluation system - GRADE). Lastly, we have addressed the possibility of planning future research via NMAs. Thus, we can conclude that NMAs could be of great value to clinical practice.

Is sonication superior to dithiothreitol in diagnosis of periprosthetic joint infections? A meta-analysis.

PURPOSE: Even though effective techniques in diagnosis of periprosthetic joint infections (PJIs) have been developed, the optimal modality has yet to be determined. The present meta-analysis aimed to compare the diagnostic accuracy of dithiothreitol (DTT) and sonication against the Musculoskeletal Infection Society criteria in patients undergoing revision joint surgery. METHODS: We searched the PubMed, Scopus, and Central Cochrane register of controlled trials as well as gray literature until the 9th of November, 2021. We included articles considering the comparative diagnostic accuracy of sonication and DTT in adult patients having revision hip and knee arthroplasty for septic or aseptic reasons. We calculated pooled sensitivity, specificity, and diagnostic accuracy of the above diagnostic techniques against the Musculoskeletal Infection Society (MSIS) criteria and created receiver operating characteristics (ROC) curves to enable comparisons between each other. The quality of included papers was evaluated utilizing QUADAS-2 and QUADAS-C tools. RESULTS: Data from five comparative studies totaling 726 implants were pooled together. The diagnostic accuracy of DTT and sonication were 86.7% (95% CI 82.7 to 90.1) and 83.9% (95% CI 79.7 to 87.5), respectively. Pooled sensitivity and specificity showed no statistically significant differences between DTT and sonication (0.7 [95% CI 0.62 to 0.77] vs 0.72 [95% CI 0.65 to 0.78], p = 0.14; and 0.99 [95% CI 0.97 to 1] vs 0.97 [95% CI 0.93 to 0.99], p = 5.5, respectively). CONCLUSIONS: This meta-analysis did not identify any clinically meaningful difference between the diagnostic potential of sonication and the chemical-based biofilm dislodgment methods. This finding remained robust after adjusting for the administration of antibiotics prophylaxis, implementation of the polymerase chain reaction of sonicated fluid, and study quality.

The reactome pathway knowledgebase 2022.

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.

Which is the optimal minimally invasive treatment for osteoid osteoma of the hip? A systematic review and proportional meta-analysis.

BACKGROUND: Osteoid osteomata comprise approximately 10% of benign bone tumours, with 20% of them being located in the proximal femur and 1-3% in the pelvis. In this meta-analysis, we sought to investigate positive and negative outcomes relating to minimally invasive surgery (MIS), which has superseded open resection and conservative measures over the last decades. METHODS: We searched the PubMed, CENTRAL and grey literature for completed studies published until 10 August 2020. Articles with a minimum of ten patients diagnosed with osteoid osteomata of the proximal femur and/or acetabulum were included. Primary outcomes were success rates, complications and recurrences following treatment. Delays in diagnosis were also recorded. We conducted random effects meta-analysis of success rates for MIS modalities using MedCalc statistical software. Quality was assessed with a modified Delphi checklist. RESULTS: Sixteen case-series were identified. Success rates for computed-tomography (CT)-guided radiofrequency ablation (RFA), CT-guided percutaneous resection drilling and arthroscopic resection were 98.2% (95% CI 95.8-99.5), p = 0.47; 91.5% (95% CI 81.1-97.9), p = 0.06; and 98% (95% CI 89.3-99.7), p = 0.95, respectively. Both RFA and percutaneous drilling resection were associated with two iatrogenic femoral fractures. Arthroscopic removal was not associated with any complications. Definitive diagnosis was established at least six months after symptom onset in up to 43% of patients. CONCLUSIONS: RFA could be the most effective treatment options for patients suffering from osteoid osteomata of the hip. Arthroscopy could be potentially as effective as RFA as long as further large-scale studies confirm its efficacy and safety. Reported complications stemming from these modalities were sparse in nature. In order to avoid inordinate diagnostic delays, a high index of suspicion and low threshold for CT scan investigation is required.

Elastic Intramedullary Nails in the Treatment of Multi-Segmental Humeral Fracture in a Polytrauma Patient.

A polytrauma patient with a life-threatening condition is a quite demanding situation due to special considerations regarding the time, the way, and the sequence of the necessary procedures. Elastic intramedullary nails (EIN) could be used under these conditions for adult patients with humeral fractures requiring fixation. Here we present a case of a multi-segmental closed humerus fracture in a polytrauma patient treated by EIN. The general condition of the patient and the need for multiple surgical procedures required the selection of a minimally invasive and time-saving fixation technique. The patient's follow-up was uneventful with complete healing of the humeral fracture; the functional scores results are excellent at five years post operatively. A review of the literature revealed limited published cases of humeral fractures (128 patients) treated by EIN, despite the fact that the results are quite encouraging. Based on our results and the current literature, we believe that EIN could become an effective treatment choice for multi-level humerus fractures, especially in damage control surgery.

Rationalising animal research synthesis in orthopaedic literature.

Systematic reviews in orthopaedic literature are frequently criticised for offering inconsistent conclusions. On top of that, high-quality randomized human evidence on crucial orthopaedic topics is more often than not lacking. In this situation, pooling animal literature could offer an excellent insight into unanswered critical clinical questions, thus potentially improving healthcare. In this paper, we sought to present the rationale and basic principles governing meta-analysis of animal research. More specifically, we elaborated on the available evidence-based methods to achieve a scientifically sound animal data synthesis. In addition, we discussed result interpretation, strength of recommendations and clinical implications based on the results of these meta-analytic modalities.

Preventing Staphylococcus aureus stainless steel-associated infections in orthopedics. A systematic review and meta-analysis of animal literature.

Surgical site infection in the presence of orthopedic implants poses significant healthcare and socioeconomic burden. To assess the potential of various prevention strategies against Staphylococcus-induced stainless steel-associated infections, a review of animal evidence was designed. The databases of PubMed, Embase, and CENTRAL were searched until March 10, 2020, for articles including animal models with stainless steel instrumentation and techniques to prevent Staphylococcus infection. We conducted a random-effects meta-analysis of standardized mean differences (SMD) with subgroup analysis linked to various protection strategies and we recorded complications. Quality was assessed with the SYRCLE's risk of bias tool. Twenty-five studies were included. Combined active coating (featuring organic antibacterial compound release) and degradable passive finishing (lipid- or polymer-based structure modification reducing bacterial adhesion) was favored over untreated controls (SMDs for methicillin-sensitive Staphylococcus aureus [MSSA] and methicillin-resistant Staphylococcus aureus [MRSA] were -3.46, 95% CI [-4.53 to -2.4], p < .001 [n = 4 head-to-head comparisons]; and -6.67, 95% CI [-10.53 to -3], p < .001 [n = 5 head-to-head comparisons], respectively). Systemic vitamin D supplementation and systemic antibiotic administration with or without local antibiotics demonstrated favorable outcomes against MSSA infection. On the contrary, no benefit was seen following vaccination. Of note, no side effects were documented. On the basis of data gathered from eight studies, which comprised 294 animals, a bioresorbable polymer- or lipid-based surface modification supplemented with organic coating yielded improved infection-related outcomes against MSSA and MRSA stainless steel infections, and therefore, this strategy could be further investigated in human research.

Is coating of titanium implants effective at preventing Staphylococcus aureus infections? A meta-analysis of animal model studies.

AIM OF THE STUDY: To assess the effects of the available coating methods against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) biofilm development on titanium implants. METHODS: We searched the MEDLINE, Embase, and CENTRAL databases until May 18, 2019, for studies that used animal models of infections to evaluate various titanium implant coating methods to prevent S. aureus infection. Twenty-seven studies were eligible for inclusion in qualitative synthesis. Of those, twenty-three were considered in pair-wise meta-analysis. In addition, subgroup analysis of implant protection strategies relative to uncoated controls was performed, and any adverse events stemming from the coating applications were reported. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies. RESULTS: Meta-analysis showed that active coating with antibiotics was favoured over uncoated controls (standardised mean differences [SMD] for MRSA and MSSA were - 2.71 [95% CI, - 4.24 to - 1.18], p = 0.0005, and - 2.5 [- 3.79 to - 1.22], p = 0.0001, respectively). Likewise, large effect sizes were demonstrated when a combination of active and conventional non-degradable passive coatings was compared with controls (SMDs for MRSA and MSSA were - 0.62 [95% CI, - 1.15 to - 0.08], p = 0.02, and - 1.93 [95% CI, - 2.87 to - 0.98], p < 0.001, respectively). DISCUSSION/CONCLUSION: As a standalone prevention method, active titanium coating with antibiotics yielded promising results against both MSSA and MRSA. Combinations between active and non-degradable passive coatings, potentially allowing for sustained antimicrobial substance release, provided consistent hardware infection protection. Thus, we recommend that future research efforts focus on combined coating modalities against S. aureus biofilm infections in the presence of titanium implants. SYSTEMATIC REVIEW REGISTRATION: CRD42019123462.

Flow characteristics and alkalinity of novel bioceramic root canal sealers.

OBJECTIVE: This study aimed to examine the physical properties (pH and flow) of 2 novel bioceramic sealers. MATERIALS AND METHODS: The tested sealers were a calcium hydroxide sealer (Sealapex) and 2 bioceramic sealers (BioRoot RCS and TotalFill BC Sealer). Flow measurements were conducted according to ISO 6876/2012, with a press method of 0.05 mL of sealer. The pH of fresh samples was tested immediately after manipulation, while set samples were stored for 3 times the recommended setting time. The predetermined time intervals ranged from 3 minutes to 24 hours for fresh samples and from 10 minutes to 7 days and 4 weeks for the set samples. Analysis of variance was performed, with p = 0.05 considered indicating significance. RESULTS: The mean flow values were 26.99 mm for BioRoot, 28.19 for Sealapex, and 30.8 mm for TotalFill BC Sealer, satisfying the ISO standard. In the set samples, BioRoot RCS had higher pH values at 24 hours to 1 week after immersion in distilled water. At 2 weeks, both bioceramic sealers had similar pH values, greater than that of Sealapex. In the fresh samples, the bioceramic sealers had significantly higher initial pH values than Sealapex (p < 0.05). At 24 hours post-immersion, all sealers showed an alkaline pH, with the highest pH observed for TotalFill. CONCLUSIONS: The TotalFill BC Sealer demonstrated the highest flow. The bioceramic sealers initially presented higher alkaline activity than the polymeric calcium hydroxide sealer. However, at 3 and 4 weeks post-immersion, all sealers had similar pH values.

Erratum: Nutritional habits and free grazing regimen of productive animals along with specific ingredients are influential factors for the antioxidant properties of milk: From farm to market.

[This corrects the article DOI: 10.3892/br.2020.1301.].

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis.

Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity. We compared B cell rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumor associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.

Nutritional habits and free grazing regimen of productive animals along with specific ingredients are influential factors for the antioxidant properties of milk: From farm to market.

Milk is a fundamental product of animal origin for human health and well-being. It possesses crucial biological properties, which depend on its composition and production methodology. To this end, one of the aims of the present study was to assess the impact of the nutritional and dwelling patterns of productive animals on the antioxidant potency of their generated milk. Thus, samples of sheep milk were collected for 30 consecutive days during the spring months from 5 different farms with different traits and its antioxidant activity was measured. Furthermore, this study aimed to evaluate the antioxidant capacity of 15 commercially available milk samples of different animal origin (i.e., cow and buffalo) and type (i.e., full-fat, light and chocolate) derived from 5 different companies. For all the experiments, the assay that examines the ability of the milk samples to reduce the DPPH• radical was used. It was thus found that the free-grazing regimen of the farm sheep dwelling at high altitude resulted in the production of milk with a greater antioxidant potential. On the other hand, it was also found that the samples of chocolate milk exhibited notably mote potent antioxidant activity than the full-fat and light samples, obviously due to the excessively high composition in antioxidant molecules present in cocoa. From this study that holistically examined the antioxidant properties of milk derived from three different productive animal species, it becomes evident that the nutritional and grazing practices, as well as specific ingredients (i.e., cocoa) lead to the generation of milk with high added biological value.

Do External Supports Improve Dynamic Balance in Patients with Chronic Ankle Instability? A Network Meta-analysis.

BACKGROUND: To improve ankle stability in patients who have experienced an ankle sprain with residual symptoms of instability and/or objective joint laxity, external supports (such as taping, bracing, and orthotic insoles) are used sometimes. However, available randomized trials have disagreed on whether restraints improve balance in those individuals. In this situation, a network meta-analysis can help because it allows for comparing multiple treatments simultaneously, taking advantage not only of direct but also indirect evidence synthesis. QUESTIONS/PURPOSES: The aim of this network meta-analysis was to assess (1) the impact of taping and orthotic devices on dynamic postural control in individuals with ankle instability and (2) the presence of a placebo effect in participants treated with sham taping and complications resulting from the administered treatments. METHODS: We searched the PubMed, Scopus, and CENTRAL databases up to February 13, 2019 for completed studies. Randomized trials assessing the results of real and/or sham taping, wait-and-see protocols, ankle bracing, and foot orthotics for ankle instability as determined by one or more ankle sprains followed by ongoing subjective symptoms and/or mechanical laxity were included. We evaluated dynamic postural control in terms of the Star Excursion Balance Test in the posteromedial direction (SEBT-PM), which is considered the most representative of balance deficits in patients with ankle instability. Standardized mean differences were re-expressed to percentage differences in SEBT-PM, with higher scores representing possible improvement. Subsequently, those data were checked against the established minimal detectable change of 14% for this scale to make judgements on clinical importance. We also assessed the presence of a placebo effect by comparing the results of sham taping with no treatment and complications resulting from the administered treatments. Additionally, we judged the quality of trials using the Cochrane risk of bias tool and quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. A total of 22 trials met our inclusion criteria, 18 of which were deemed to be at a low risk of bias. A network of treatments consisting of 13 studies was created, and the level of evidence was judged to be high. As far as participants' allocation to treatment arms, 85 patients followed a wait-and-see protocol, 29 received placebo taping, 99 were treated with taping, 16 were treated with bracing, 27 were administered insoles, and six individuals were offered a combination of insoles with bracing. Of note, with statistical power set at 80%, a minimum of 16 patients per treatment group was required to provide sufficient statistical power and detect a SEBT-PM percentage difference of 14%. RESULTS: A network meta-analysis did not demonstrate a benefit of taping or bracing over no treatment (percentage difference in SEBT-PM between taping and bracing versus control: -2.4 [95% CI -6 to 1.1]; p = 0.18, and -7.5 [95% CI -15.9 to 1]; p = 0.08, respectively). This was also the case for sham taping because the measurement increase failed to exceed the minimal detectable change (percentage difference in SEBT-PM between sham taping and untreated control: -1.1 [95% CI -6.9 to 4.7]; p = 0.72). Importantly, there were no reported adverse events after treatment application. CONCLUSIONS: Evidence of moderate strength indicated that external supports of any type were no more effective than controls in improving dynamic postural control in patients with at least one ankle sprain and residual functional or mechanical deficits. Therefore, implementing those tools as a standalone treatment does not appear to be a viable strategy for the primary management of ankle instability. It is conceivable that combinations of rehabilitation and external supports could be more effective than external supports alone, and future trials should evaluate the potential of such combinations in enhancing not only clinician-reported but also patient-oriented outcomes using long-term follow-up measurements. LEVEL OF EVIDENCE: Level I, therapeutic study.