Adequacy of thyroid hormone replacement for people with hypothyroidism in real-world settings: A systematic review and meta-analysis of observational studies.

OBJECTIVE: Thyroid hormone under-replacement and over-replacement are associated with adverse health outcomes. This systematic review aimed to evaluate the extent of thyroid hormone replacement adequacy for patients with known hypothyroidism in real-word settings, excluding those receiving thyroid hormone suppressive therapy as thyroid cancer treatment. DESIGN: Four electronic databases (Embase [Ovid], Medline [Ovid], PubMed and SCOPUS) were searched for published and unpublished observational studies until 12 December 2022. The results of the studies were meta-analysed to calculate pooled prevalence estimates for thyroid hormone supplementation adequacy, over-replacement and under-replacement. Quality assessment of studies was performed using the Joanna-Briggs appraisal tool for prevalence studies. RESULTS: Seven studies with a total of 4230 patients were eligible for quantitative synthesis. The pooled prevalence estimates of adequate thyroid replacement, over-replacement and under-replacement were 0.55 (95% confidence interval [CI]: 0.49-0.60, p = .001), 0.20 (95% CI: 0.14-0.27, p = .001) and 0.24 (95% CI: 0.13-0.36, p = .001), respectively. Four studies subclassified hypothyroidism and hyperthyroidism into overt and subclinical. The pooled prevalence of overt and subclinical hyperthyroidism was 0.04 (95% CI: 0.00-0.11, p = .01) and 0.17 (95% CI: 0.09-0.27 p = .001), respectively. For overt and subclinical hypothyroidism, the pooled prevalence was 0.02 (95% CI: 0.01-0.03, p = .001) and 0.20 (95% CI: 0.12-0.29, p = .001), respectively. CONCLUSIONS: On average, approximately half of patients with hypothyroidism are only treated to target euthyroidism. In real-world practice, a significant number of patients are over-treated or under-treated, leading to adverse healthcare outcomes. It is imperative that more effective thyroid monitoring strategies be implemented, with an emphasis on primary care thyroid function monitoring, to minimise inappropriate thyroid replacement treatments and optimise healthcare outcomes at a population level.

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%.

Is nanomaterial- and vancomycin-loaded polymer coating effective at preventing methicillin-resistant Staphylococcus aureus growth on titanium disks? An in vitro study.

PURPOSE: Periprosthetic joint infections induced by methicillin-resistant Staphylococcus aureus (MRSA) pose a major socioeconomic burden. Given the fact that MRSA carriers are at high risk for developing periprosthetic infections regardless of the administration of eradication treatment pre-operatively, the need for developing new prevention modalities is high. METHODS: The antibacterial and antibiofilm properties of vancomycin, Al2O3 nanowires, and TiO2 nanoparticles were evaluated in vitro using MIC and MBIC assays. MRSA biofilms were grown on titanium disks simulating orthopedic implants, and the infection prevention potential of vancomycin-, Al2O3 nanowire-, and TiO2 nanoparticle-supplemented Resomer® coating was evaluated against biofilm controls using the XTT reduction proliferation assay. RESULTS: Among the tested modalities, high- and low-dose vancomycin-loaded Resomer® coating yielded the most satisfactory metalwork protection against MRSA (median absorbance was 0.1705; [IQR = 0.1745] vs control absorbance 0.42 [IQR = 0.07]; p = 0.016; biofilm reduction was 100%; and 0.209 [IQR = 0.1295] vs control 0.42 [IQR = 0.07]; p < 0.001; biofilm reduction was 84%, respectively). On the other hand, polymer coating alone did not provide clinically meaningful biofilm growth prevention (median absorbance was 0.2585 [IQR = 0.1235] vs control 0.395 [IQR = 0.218]; p < 0.001; biofilm reduction was 62%). CONCLUSIONS: We advocate that apart from the well-established preventative measures for MRSA carriers, loading implants with bioresorbable Resomer® vancomycin-supplemented coating may decrease the incidence of early post-op surgical site infections with titanium implants. Of note, the payoff between localized toxicity and antibiofilm efficacy should be considered when loading polymers with highly concentrated antimicrobial agents.

Immediate or interval abscess tonsillectomy? A systematic review and meta-analysis.

OBJECTIVES: Peritonsillar abscess is a common complication of acute tonsillitis. However, no consensus has been reached yet on the optimal treatment of this condition. Therefore, this study aimed to compare clinical outcomes of immediate and interval abscess tonsillectomy. METHODS: The databases of PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for completed studies published until the 1st of November 2021. Comparative studies assessing intraoperative and postoperative outcomes of immediate and interval abscess tonsillectomy were considered, with the primary outcome being postoperative hemorrhage. Operative time, intraoperative blood loss, postoperative pain, and duration of hospital stay were classed as secondary outcomes. A random-effects pairwise meta-analysis of both randomized and non-randomized trials was conducted. Subgroup analysis linked to the randomization of trials was executed. Quality assessment was performed, utilizing the Cochrane risk of bias tool and ROBINS-I tool for randomized and non-randomized trials, respectively. RESULTS: Data from 265 cases stemming from six trials were pooled together. For postoperative bleeding rates, no statistically significant difference between immediate and interval tonsillectomy was detected (OR = 1.26; 95% CI 0.27, 5.86; p = 0.77). By contrast, longer hospital stay was observed for patients subjected to interval tonsillectomy (SMD = - 0.78; CI - 1.39 to- 0.17; p = 0.01). For operative time and intraoperative blood loss, no statistically significant difference was noticed between immediate and interval tonsillectomy (SMD = 1.10; 95% CI - 0.13, 2.33; p = 0.08; and SMD = 0.04; 95% CI - 0.49, 0.57; p = 0.88; respectively). CONCLUSIONS: This study shows that quinsy tonsillectomy appears to be a safe method, providing full abscess drainage and instant relief of the symptoms. Moreover, quinsy tonsillectomy was not associated with a statistically higher postoperative hemorrhage incidence rate than immediate tonsillectomy.

In vitro Inhibition of Biofilm Formation on Silicon Rubber Voice Prosthesis: Α Systematic Review and Meta-Analysis.

INTRODUCTION: Biofilm formation on voice prostheses is the primary reason for their premature implant dysfunction. Multiple strategies have been proposed over the last decades to achieve inhibition of biofilm formation on these devices. The purpose of this study was to assess the results of the available in vitro biofilm inhibition modalities on silicone rubber voice prostheses. METHODS: We conducted a systematic search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases up to February 29, 2020. A total of 33 in vitro laboratory studies investigating the efficacy of different coating methods against Candida, Staphylococcus, Streptococcus, Lactobacilli, and Rothia biofilm growth on silicone rubber medical devices were included. Subgroup analysis linked to the type of prevention modality was carried out, and quality assessment was performed with the use of the modified CONSORT tool. RESULTS: Data from 33 studies were included in qualitative analysis, of which 12 qualified for quantitative analysis. For yeast biofilm formation assessment, there was a statistically significant difference in favor of the intervention group (standardized mean difference [SMD] = -1.20; 95% confidence interval [CI] [-1.73, -0.66]; p < 0.0001). Subgroup analysis showed that combined methods (active and passive surface modification) are the most effective for biofilm inhibition in yeast (SMD = -2.53; 95% CI [-4.02, -1.03]; p = 0.00001). No statistically significant differences between intervention and control groups were shown for bacterial biofilm inhibition (SMD = -0.09; 95% CI [-0.68, 0.46]; p = 0.65), and the results from the subgroup analysis found no notable differences between the surface modification methods. After analyzing data on polymicrobial biofilms, a statistically significant difference in favor of prevention methods in comparison with the control group was detected (SMD = -2.59; 95% CI [-7.48, 2.31]; p = 0.30). CONCLUSIONS: The meta-analysis on biofilm inhibition demonstrated significant differences in favor of yeast biofilm inhibition compared to bacteria. A stronger inhibition with the application of passive or combined active and passive surface modification techniques was reported.

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.

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.

Return-to-Sport Rate and Activity Level Are High Following Arthroscopic All-Inside Meniscal Repair With and Without Concomitant Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To systematically review the literature of return-to-sport outcomes following all-inside meniscus repair and evaluate whether concomitant anterior cruciate ligament reconstruction (ACLR) influenced these outcomes. METHODS: A systematic review of the MEDLINE, PubMed, Embase, and Cochrane Registry of Systematic Reviews databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two reviewers examined all literature pertaining to sport outcomes following all-inside meniscal repair. Studies were included if they had a 12-month minimum follow-up and reported return to sport rate, Tegner, or Knee injury and Osteoarthritis Outcome Score (KOOS) Sport outcomes. Studies with meniscal repair techniques other than the all-inside technique were excluded. Studies were not excluded if they contained patients receiving concomitant ACLR. Study quality was evaluated with the Methodological Index for Nonrandomized Studies. RESULTS: Nineteen studies comprising 872 patients were included in this investigation. The weighted average patient age was 28.7 (range 14.1-42.1) years, and the weighted average follow-up was 56.0 (range 18.0-155.0) months. The mean Methodological Index for Nonrandomized Studies score was 14.4 ± 3.7. Ten investigations reported both preoperative (range 2.3-3.5) and postoperative (range 4.0-7.3) Tegner outcomes, with scores at final follow-up greater in each of the 10 reporting investigations. KOOS Sport outcomes were examined in 5 investigations, with scores at follow-up ranging from 63.6 to 91. Three studies reported a return to sport rate ranging from 89.6 to 90% at follow-up. Four investigations compared sport-related outcomes between isolated meniscal repair and meniscal repair with concomitant ACLR. Two such studies reported no difference between the 2 cohorts, 1 favored the isolated cohort, and 1 favored the combined cohort. CONCLUSIONS: This systematic review found a 90% return-to-sport rate and high postoperative activity level following all-inside meniscal repair, as assessed by KOOS Sport and Tegner activity scales. Further, concurrent ACLR did not significantly affect these outcomes. LEVEL OF EVIDENCE: IV, systematic review of level I-IV studies.

A computer tablet software can quantify the deviation of scapula medial border from the thoracic wall during clinical assessment of scapula dyskinesis.

PURPOSE: Aim of this study is to establish an objective and easily applicable method that will allow clinicians to quantitatively assess scapular dyskinesis during clinical examination using a computer tablet software. Hypothesis is that dyskinetic scapulae present greater motion-deviation from the thoracic wall-compared to the non-dyskinetic ones and that the software will be able to record those differences. METHODS: Twenty-five patients and 19 healthy individuals were clinically evaluated for the presence of dyskinesis or not. According to the clinical diagnosis, the observations were divided into three groups; A. Dyskinetic scapulae with symptoms (n = 25), B. Contralateral non-dyskinetic scapulae without symptoms (n = 25), C. Healthy control scapulae (n = 38). Then, all individuals were tested using a tablet with the PIVOT™ image-based analysis software (PIVOT, Impellia, Pittsburgh, PA, USA). The motion produced by the scapula medial border and inferior angle deviation from the thoracic wall was recorded. RESULTS: The deviation of the medial border and inferior angle of the scapula from the thoracic wall was 24.6 ± 7.3 mm in Group A, 14.7 ± 4.9 mm in Group B, and 12.4 ± 5.2 mm in Group C. The motion recorded in the dyskinetic scapulae group was significantly greater than both the contralateral non-dyskinetic scapulae group (p < 0.01) and the healthy control scapulae group (p < 0.01). CONCLUSION: The PIVOT™ software was efficient to detect significant differences in the motion between dyskinetic and non-dyskinetic scapulae. This system can support the clinical diagnosis of dyskinesis with a numeric value, which not only contributes to scapula dyskinesis grading but also to the evaluation of the progress and efficacy of the applied treatment, thus providing a feedback to the clinician and the patient. LEVEL OF EVIDENCE: IV, laboratory study.

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.

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.

Piezoelectric or Conventional Osteotomy in Rhinoplasty? A Systematic Review and Meta-Analysis of Clinical Outcomes.

INTRODUCTION: Osteotomy of nasal bones in rhinoplasty is associated with postsurgical morbidities. Recent evidence has suggested that a surgical method applying piezoelectric ultrasound waves for nasal osteotomies in rhinoplasty reduces soft tissue damage and causes less postsurgical morbidities compared to conventional methods. The purpose of this study is to compare clinical outcomes of piezoelectric and conventional lateral nasal osteotomies in rhinoplasty. METHODS: We searched PubMed, CENTRAL, and Web of Science up to 17 August 2019 for studies comparing postoperative outcomes of piezoelectric and conventional lateral osteotomies in rhinoplasty. We included studies comparing results of patients subjected to piezoelectric or conventional lateral nasal osteotomies in rhinoplasty. For outcomes, we considered postoperative pain, eyelid edema, periorbital ecchymosis, and intraoperative mucosal injury. RESULTS: For eyelid edema, a statistically significant difference in favor of piezoelectric osteotomy was documented within the first 3 postoperative days (standardized mean difference [SMD] = -0.65; 95% CI = -1.18, -0.12, p = 0.02; I2 = 69%) and on postoperative day 7 (SMD = -0.69; 95% CI = -1.47, -0.09; p = 0.08; I2 = 85%). This was also the case for periorbital ecchymosis within the first 3 postoperative days (SMD = -0.85; 95% CI = -1.42, -0.28; p = 0.004; I2 = 72%) and on postoperative day 7 (SMD = -0.52; 95% CI = -0.79, -0.24; p = 0.0003; I2 = 71%). Intraoperative mucosal injury (OR = 0.06; 95% CI = 0.01, 0.53; p = 0.01; Ι2 = 0%) and postoperative pain (SMD = -0.99; 95% CI = -1.78, -0.11; p = 0.01; I2 = 49%) were also statistically lower during piezoelectric osteotomies. CONCLUSIONS: This study shows that lateral piezoelectric osteotomy in rhinoplasty decreases postoperative pain, edema, ecchymosis, and intraoperative mucosa injuries compared to the conventional osteotomy technique with a chisel. Piezoelectric osteotomies are especially associated with less postoperative edema and ecchymosis in osteotomies not executed under direct vision.

Is Implant Coating With Tyrosol- and Antibiotic-loaded Hydrogel Effective in Reducing Cutibacterium (Propionibacterium) acnes Biofilm Formation? A Preliminary In Vitro Study.

BACKGROUND: Studies have suggested that Cutibacterium acnes (formerly known as Propionibacterium) is the most frequently isolated pathogen after shoulder arthroplasty. To address the burden of periprosthetic joint infections associated with this pathogen, new prevention methods are needed. Tyrosol has a promising record of effectiveness in the field of biofilm-associated infections; however, to our knowledge, it has not been tested against C. acnes thus far. QUESTIONS/PURPOSES: In this in vitro study, we asked: (1) Is tyrosol effective in inhibiting and eradicating C. acnes planktonic growth? (2) Is there synergy between tyrosol and rifampicin? (3) Is supplementation of hydrogel with tyrosol at the minimum inhibitory and subinhibitory concentrations efficacious in reducing free-floating C. acnes growth? (4) Is implant hydrogel coating (either alone or combined with tyrosol, rifampicin, or vancomycin) beneficial in reducing C. acnes biofilm formation? (5) Is the administration of soluble tyrosol an effective measure against C. acnes biofilm formation? METHODS: We assessed C. acnes planktonic growth and eradication by inspecting visually the results of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. We also evaluated macroscopically the presence of synergy among tyrosol and rifampicin by means of the MIC checkerboard testing. Thereafter, we addressed colorimetrically the efficacy of tyrosol-loaded Defensive Antibacterial Coating (DAC®) hydrogel against the C. acnes free-floating form by means of the XTT cell proliferation reduction assay. Then, we explored photometrically the effect of hydrogel and soluble tyrosol at reducing C. acnes biofilm formation on titanium alloy disks that simulated orthopaedic implants by using the minimum biofilm inhibition concentration assay. In particular, 16 disks were sequentially allocated to each of the following testing conditions: (1) hydrogel alone; (2) tyrosol-loaded hydrogel; (3) rifampicin-supplemented hydrogel; (4) vancomycin-loaded hydrogel; and (5) soluble tyrosol. Subsequently, implants were sonicated and cell viability was evaluated in terms of the XTT assay. RESULTS: Tyrosol was effective in inhibiting C. acnes planktonic (free-floating) growth demonstrating MIC values of 63 mM (9 mg/mL) and MBC values of 250 mM (35 mg/mL). Concerning synergy assessment, the checkerboard testing revealed additivity among tyrosol and rifampicin with a fractional inhibitory concentration index of 0.56. In addition, a hydrogel coating with tyrosol at the MIC showed no difference in the inhibition of free-floating C. Acnes form over control (median absorbance [MA] for tyrosol-supplemented hydrogel versus control groups were 0.21 [interquartile range {IQR}, 0.19-0.24] versus 0.26 [IQR, 0.23-0.31], p = 0.066). Furthermore, loaded hydrogel with tyrosol at 597 mg/mL (1 M) was no more effective than control in reducing C. acnes biofilm formation (MAs for tyrosol versus control were 0.12 [IQR, 0.11-0.13] versus 0.14 [IQR, 0.12-0.16], respectively; p = 0.076). This was also the case when we considered hydrogel in conjunction with vancomycin and rifampicin (MAs for vancomycin at 2% and 5% and rifampicin at 1% versus biofilm control were 0.139 [IQR, 0.133-0.143] and 0.141 [IQR, 0.133-0.143] and 0.135 [IQR, 0.128-0.146] versus 0.142 [IQR, 0.136-0.144], correspondingly). In contrast, soluble tyrosol at 597 mg/mL (1 M) inhibited biofilm formation compared to control (MAs for tyrosol and control groups were 0.11 [IQR, 0.09-0.13] versus 0.13 [IQR, 0.12-0.14], p = 0.007). CONCLUSIONS: Although the implant coating with hydrogel (either pure or supplemented with antimicrobial agents) did not diminish C. acnes biofilm development in vitro, soluble tyrosol at 597 mg/mL (1 M) exceeded the meaningful biofilm inhibition threshold of 80%. CLINICAL RELEVANCE: The results of the current preclinical investigation did not support the use of a fast, bioresorbable hydrogel as a coating method against C. acnes biofilms. Instead, direct local administration of soluble tyrosol at high concentrations should be further tested in future animal studies.

Does Multimodal Rehabilitation for Ankle Instability Improve Patients' Self-assessed Functional Outcomes? A Network Meta-analysis.

BACKGROUND: Although there are many nonsurgical treatment options for the primary management of chronic ankle instability, the most effective nonoperative intervention has not been defined. QUESTIONS/PURPOSES: The purpose of this study was to perform a network meta-analysis to compare the results of different standalone and/or combined nonsurgical interventions on chronic ankle instability as measured by (1) the Cumberland Ankle Instability Tool (CAIT) at 0 to 6 months after treatment and (2) treatment-related complications. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus in August 2017 for completed studies published between 2005 and 2016. We conducted random-effects pairwise and network meta-analysis considering randomized trials, which compared the effects of various nonoperative therapies for ankle instability. Studies assessing patients with functional ankle instability and/or mechanical ankle instability and/or recurrent ankle sprains were eligible for inclusion. After combining data from self-administered questionnaires, we analyzed patient self-reported outcomes of function at the end of the rehabilitation period and 1 to 6 months after treatment. We thereafter reexpressed standardized mean differences to mean differences with CAIT. For this instrument, scores vary between 0 and 30, and higher scores indicate better ankle stability. We included 21 trials involving 789 chronically unstable ankles. The rehabilitation interventions included, but were not limited to, balance training, strengthening exercises, a combination of the balance and strengthening exercises, manual therapy, and multimodal treatment. The implemented multistation protocols were targeted at four main areas of rehabilitation (ROM, balance, strength, and overall activity). Control was defined as placebo and/or wait and see. Treatment-related complications were defined as any major or minor adverse event observed after rehabilitation as reported by the source studies. Statistically, we did not detect significant inconsistency in the network meta-analysis. We also assessed the quality of the trials using the Cochrane risk of bias tool and judged 12, eight, and one studies to be at a low, unclear, and high risk of bias, respectively. We also considered the quality of evidence to be of moderate strength utilizing the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We defined the minimum clinically important difference (MCID) in the CAIT to be 3 points. RESULTS: A 4-week supervised rehabilitation program, which included balance training, strengthening, functional tasks, and ROM exercises, was favored over control according to the results of four trials by a clinically important margin (mean difference between multimodal and control groups in the CAIT was -10; 95% confidence interval [CI], -16 to -3; p = 0.001). Among the standalone interventions, only balance training was better than control according to the findings of seven trials (mean difference between balance training and control in the CAIT was -5; 95% CI, -10 to -0.03; p = 0.049); this difference likewise exceeded the MCID and so is believed to be a clinically important difference. Adverse events associated with the enrolled rehabilitation protocols were transient, mild, and uncommon. CONCLUSIONS: Although a supervised impairment-based program after chronic ankle instability was superior to control, we note that followup in the included trials tended to be short and inconsistent, although the effect size exceeded the MCID and so likely would be identified as clinically important by patients. Future randomized trials should determine whether the short-term benefits of these interventions are sustained over time. LEVEL OF EVIDENCE: Level I, therapeutic study.

Proximal versus distal metatarsal osteotomies for moderate to severe hallux valgus deformity: a systematic review and meta-analysis of clinical and radiological outcomes.

PURPOSE: The conventional surgical treatment of moderate to severe hallux valgus (HV) deformity includes proximal metatarsal osteotomies (PMOs). Recent evidence suggests that the extension of indications for distal metatarsal osteotomies (DMOs) may result in comparable outcomes. The purpose of this study was to compare the efficacy of proximal with that of distal metatarsal osteotomies for moderate to severe HV deformity. METHODS: We searched PubMed, Scopus, and CENTRAL up to 25 July 2017. We included studies comparing the results of proximal and distal metatarsal osteotomies for moderate to severe HV deformity. The primary outcomes included the assessment of the first intermetatarsal angle (IMA) and American Orthopaedic Foot and Ankle Society (AOFAS) scoring system. For the secondary outcomes, we considered the hallux valgus angle, sesamoid position, and participants' satisfaction. We also reported and analyzed complications. We evaluated all outcomes in the short-term (≤ 1 year) and medium-term (> 1 and < 10 years). The quality assessment was performed using the Cochrane risk of bias and ROBINS-I tools for randomized and non-randomized studies, respectively. RESULTS: Data from 696 cases were considered in this review. For the assessment of the first IMA, there was a slight advantage in favour of the PMO group in the medium term (SMD was - 0.38, 95% CIs - 0.65 to - 0.12, p < 0.05, I2 = 21%). For the rest outcomes, we did not detect any significant differences between the intervention groups. CONCLUSIONS: For clinical and radiological outcomes, the quantitative synthesis demonstrated that there were no significant differences between PMO and DMO groups in the medium term. These findings were supported by data from non-randomized studies. For the reported complications, we did not detect any significant differences between the intervention groups.

Injection therapies for plantar fasciopathy ('plantar fasciitis'): a systematic review and network meta-analysis of 22 randomised controlled trials.

OBJECTIVE: To compare the efficacy of different injection therapies for plantar fasciopathy (historically known as 'plantar fasciitis'). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Electronic databases (MEDLINE, CENTRAL, Web of Science and Scopus) were searched up to 11 July 2015 for completed studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We considered randomised trials comparing various injection therapies in adults with plantar fasciopathy. The primary outcome was pain relief. Secondary outcomes included functional disability, composite and health-related outcomes. All outcomes were assessed (1) in the short term (up to 2 months), (2) the intermediate term (2-6 months) and (3) the medium term (more than 6 months to 2 years). Quality assessment was performed using the Cochrane risk of bias tool. RESULTS: We included 22 trials comprising 1216 patients. Dehydrated amniotic membrane injections were significantly superior to corticosteroids in the short term in achieving the primary and composite outcomes (mean difference (MD) in visual analogue scale (VAS) was -7.32, 95% CIs -11.2 to -3.38; and MD in the foot health status questionnaire was 31.2, 95% CIs 13.9 to 48.6, respectively). For pain relief, botulinum toxin-A provided a significant short-term advantage over placebo, which was still present at 6 months (MD in VAS was -2.9, 95% CIs -4.44 to -1.39; and MD -4.34, 95% CIs -7.18 to -1.54, respectively). SUMMARY: Although the dehydrated amniotic membrane provided significant clinical relief at 0-2 months, there were no data about this treatment at 2 months and beyond. Botulinum toxin-A injections significantly reduced pain intensity at 0-6 months. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42015017353.

'The effect of inulin addition on structural and textural properties of extruded products under several extrusion conditions': The effect of inulin addition on structural and textural properties of rice flour extrudates.

The growing consumer demand for healthy snacks has turned the interest of industry and research in the development of new ready-to-eat products, enriched with dietary fibers. Inulin is a soluble fiber with a neutral taste that promotes the good function of the intestine. Rice flour extrudates were produced under various extrusion temperatures, screw speeds, feed moisture concentrations and inulin replacement levels. The objective of this study was to investigate the effect of the material characteristics and the extrusion conditions on the structural and textural properties of the extrudates. Simple mathematical models were used for properties correlation with process conditions and through regression analysis it was revealed that there is a significant effect of extrusion temperature, screw speed, feed moisture content and inulin concentration on the final properties. Both density and maximum stress increased when moisture content and inulin concentration increased, while they decreased when extrusion temperature and screw speed increased. These results were also strengthened by scanning electron microscopy. The highest expansion ratio was presented when decreasing all process conditions apart from screw speed.

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.