Effects of brain microRNAs in cognitive trajectory and Alzheimer's disease.

microRNAs (miRNAs) have a broad influence on gene expression; however, we have limited insights into their contribution to rate of cognitive decline over time or Alzheimer's disease (AD). Given this, we tested associations of 528 miRNAs with cognitive trajectory, AD hallmark pathologies, and AD clinical diagnosis using small RNA sequencing from the dorsolateral prefrontal cortex of 641 community-based donors. We found 311 miRNAs differentially expressed in AD or its endophenotypes after adjusting for technical and sociodemographic variables. Among these, 137 miRNAs remained differentially expressed after additionally adjusting for several co-occurring age-related cerebral pathologies, suggesting that some miRNAs are associated with the traits through co-occurring pathologies while others through mechanisms independent from pathologies. Pathway enrichment analysis of downstream targets of these differentially expressed miRNAs found enrichment in transcription, postsynaptic signalling, cellular senescence, and lipoproteins. In sex-stratified analyses, five miRNAs showed sex-biased differential expression for one or more AD endophenotypes, highlighting the role that sex has in AD. Lastly, we used Mendelian randomization to test whether the identified differentially expressed miRNAs contribute to the cause or are the consequence of the traits. Remarkably, 15 differentially expressed miRNAs had evidence consistent with a causal role, laying the groundwork for future mechanistic studies of miRNAs in AD and its endophenotypes.

Genetic regulation of microRNAs in the older adult brain and their contribution to neuropsychiatric conditions.

MicroRNAs are essential post-transcriptional regulators of gene expression and involved in many biological processes; however, our understanding of their genetic regulation and role in brain illnesses is limited. Here, we mapped brain microRNA expression quantitative trait loci (miR-QTLs) using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex (dlPFC) samples of 604 older adult donors of European ancestry. miR-QTLs were identified for 224 miRNAs (48% of 470 tested miRNAs) at false discovery rate < 1%. We found that miR-QTLs were enriched in brain promoters and enhancers, and that intragenic miRNAs often did not share QTLs with their host gene. Additionally, we integrated the brain miR-QTLs with results from 16 GWAS of psychiatric and neurodegenerative diseases using multiple independent integration approaches and identified four miRNAs that contribute to the pathogenesis of bipolar disorder, major depression, post-traumatic stress disorder, schizophrenia, and Parkinson's disease. This study provides novel insights into the contribution of miRNAs to the complex biological networks that link genetic variation to disease.

Reconstitution of human tissue barrier function for precision and personalized medicine.

Tissue barriers in a body, well known as tissue-to-tissue interfaces represented by endothelium of the blood vessels or epithelium of organs, are essential for maintaining physiological homeostasis by regulating molecular and cellular transports. It is crucial for predicting drug response to understand physiology of tissue barriers through which drugs are absorbed, distributed, metabolized and excreted. Since the FDA Modernization Act 2.0, which prompts the inception of alternative technologies for animal models, tissue barrier chips, one of the applications of organ-on-a-chip or microphysiological system (MPS), have only recently been utilized in the context of drug development. Recent advancements in stem cell technology have brightened the prospects for the application of tissue barrier chips in personalized medicine. In past decade, designing and engineering these microfluidic devices, and demonstrating the ability to reconstitute tissue functions were main focus of this field. However, the field is now advancing to the next level of challenges: validating their utility in drug evaluation and creating personalized models using patient-derived cells. In this review, we briefly introduce key design parameters to develop functional tissue barrier chip, explore the remarkable recent progress in the field of tissue barrier chips and discuss future perspectives on realizing personalized medicine through the utilization of tissue barrier chips.

Synergistic clinical application of synthetic electrospun fiber wound matrix in the management of a complex traumatic wound: degloving left groin and thigh auger injury.

BACKGROUND: Managing complex traumatic soft tissue wounds involving a large surface area while attempting to optimize healing, avoid infection, and promote favorable cosmetic outcomes is challenging. Regenerative materials such as ECMs are typically used in wound care to enhance the wound healing response and proliferative phase of tissue formation. CASE REPORT: The case reported herein is an example of the efficacious use of an SEFM in the surgical management of a large complex traumatic wound involving the left lower extremity and lower abdominal region. The wound bed was successfully prepared for skin grafting over an area of 1200 cm2, making this among the largest applications of the SEFM reported in the literature. CONCLUSION: This case report demonstrates the clinical versatility of the SEFM and a synergistic approach to complex traumatic wound care. The SEFM was successfully used to achieve tissue granulation for a successful skin graft across a large surface in an anatomic region with complex topography.

Multidisciplinary expert consensus statements and recommendations for use of hypochlorous acid as a solution for negative pressure wound therapy with instillation.

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.

Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double-blind, placebo-controlled trial.

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

Navigating Institutional Review Boards.

Obtaining institutional review board (IRB) approval can be an overwhelming task, especially for new researchers. IRB approval can require many documents and steps. It is important to start the submission early, have patience throughout the process, and determine what can help expedite the process. Research cannot begin without IRB approval, which is necessary when working with human subjects. Ultimately, the researchers and IRB have the same goal of enabling good research with minimal subject risk. The goal of this article is to give an overview of the IRB for practitioners performing research in podiatric medicine and surgery.

Incidence of Acute Rejection Compared With Endomyocardial Biopsy Complications for Heart Transplant Patients in the Contemporary Era.

BACKGROUND: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the incidence of treated AR compared with EMB complications has not been compared in the contemporary era (2010-current). METHODS: The authors retrospectively analyzed 2769 EMBs obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for-cause indication, recipient and donor characteristics, EMB procedural data and pathological grades, treatment for AR, and clinical outcomes. RESULTS: The overall EMB complications rate was 1.6%. EMBs performed within 1 mo after HTx compared with after 1 mo from HTx showed significantly increased complications (OR, 12.74, P < 0.001). The treated AR rate was 14.2% in the for-cause EMBs and 1.2% in the surveillance EMBs. We found the incidence of AR versus EMB complications was significantly lower in the surveillance compared with the for-cause EMB group (OR, 0.05, P < 0.001). We also found the incidence of EMB complications was higher than treated AR in surveillance EMBs. CONCLUSIONS: The yield of surveillance EMBs has declined in the contemporary era, with a higher incidence of EMB complications compared with detected AR. The risk of EMB complications was highest within 1 mo after HTx. Surveillance EMB protocols in the contemporary era may need to be reevaluated.

Donor-Specific Antibody Testing is an Effective Surveillance Strategy for High-Risk Antibody Mediated Rejection in Heart Transplant Patients in the Contemporary Era.

Background: Pathologic antibody mediated rejection (pAMR) evaluation and donor specific antibody (DSA) testing are recommended in the first year after heart transplantation (HTx) in adult patients. Whether DSA testing adds prognostic information to contemporary pAMR surveillance has not been fully studied. Methods: This was a single center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether DSA testing contributes additional information to pAMR surveillance to better predict overall survival. Secondary endpoints included cardiac allograft dysfunction and loss. Results: A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ group had significantly lower overall survival versus the pAMR-/DSA- group (hazard ratio [HR] = 2.63; 95% confidence interval [CI], 1.35-5.11; pc = 0.013). In the pAMR+/DSA+ group, patients with cardiac allograft dysfunction, compared to those without allograft dysfunction, had significantly lower overall and cardiac survival (pc < 0.001 for both). In contrast, pAMR+/DSA+ and pAMR-/DSA- patients without cardiac allograft dysfunction showed no difference in overall and cardiac survival. Primary graft dysfunction (PGD) was a novel risk factor for development of de novo DSAs (dnDSA) three weeks post-HTx (p = 0.007). Conclusions: DSA testing as the primary surveillance method can identify high-risk pAMR+/DSA+ patients. Surveillance pAMR testing in the contemporary era may need to be reevaluated. Earlier DSA testing at 10-14 days post-HTx should be considered in PGD patients.

Clinical application of a synthetic hybrid-scale fiber matrix in a pediatric trauma patient.

INTRODUCTION: Large soft tissue defects resulting from trauma in the pediatric population are common. MLLs are a rare subset of these injuries with no standard treatment regimen. Thorough surgical debridement of these lesions is often warranted to remove necrotic tissue and contamination, which results in a large, open soft tissue defect. STSGs may be used to provide tissue coverage; however, they have limitations, including donor site morbidity and additional surgical time and cost. CASE REPORT: A 12-year-old female with a cutaneous thermal contact burn and an MLL of the right lower medial thigh declined STSG to avoid additional operations. The wound was treated with an SHSFM that is engineered to mimic the structure and architecture of human extracellular matrix and supports cellular infiltration and proliferation with minimal inflammatory response. Over a 4-month period, the SHSFM was applied 6 times at 2- to 3-week intervals, resulting in complete regranulation and wound closure with no further surgical procedures required. CONCLUSIONS: This case demonstrates the utility of the SHSFM in the management of pediatric surgical wounds and highlights the flexibility of the SHSFM in achieving the goals of both patient and physician alike.

Benefit versus Risk of Endomyocardial Biopsy for Heart Transplant Patients in the Contemporary Era.

Background: The reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the benefit of diagnosing and treating AR compared to the risk of EMB complications has not been compared in the contemporary era (2010-current). Methods: The authors retrospectively analyzed 2,769 EMB obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for cause indication, recipient and donor characteristics, EMB procedural data and pathologic grades, treatment for AR, and clinical outcomes. Results: The overall EMB complication rate was 1.6%. EMBs performed within 1 month after HTx compared to after 1 month from HTx showed significantly increased complications (OR = 12.74, p < 0.001). The treated AR rate was 14.2% in the for cause EMBs and 1.2% in the surveillance EMBs. We found the benefit/risk ratio was significantly lower in the surveillance compared to the for cause EMB group (OR = 0.05, p < 0.001). We also found the benefit to be lower than risk in surveillance EMBs. Conclusions: The yield of surveillance EMBs has declined, while for cause EMBs continued to demonstrate a high benefit/risk ratio. The risk of EMB complications was highest within 1 month after HTx. Surveillance EMB protocols in the contemporary era may need to be re-evaluated.

A synthetic hybrid-scale fiber matrix for complex surgical wounds: consensus guidelines.

Based on their own clinical experience and review of the available peer-reviewed data, the authors developed a consensus opinion on the use of an SHSFM for open wounds. The matrix has features such as varying pore sizes and fibers (ie, hybrid-scale) and is indicated for the treatment of open wounds. This report describes the design and utility of the SHSFM, its mechanism of action, and the methods of application, as well as clinical outcomes. The authors discuss their own experience and review of the published literature, then describe their protocols and rationale for the use of the SHSFM. These consensus statements include recommendations regarding appropriate wounds for use of the SHSFM, use of other wound therapies in conjunction with the SHSFM, reapplication rates, preparation methods, and additional discussions of appropriate use. This report is not a literature review, but rather is a statement of preliminary clinical experience. The consensus statements indicate that the SHSFM may be used to treat a variety of wounds and can be used to stage wounds to closure via skin grafts or by secondary intention.

Comparison of two donor-derived cell-free DNA tests and a blood gene-expression profile test in heart transplantation.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd-cfDNA and gene-expression profiling (GEP) testing in heart transplant (HTx) recipients. METHODS: This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd-cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. RESULTS: A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd-cfDNA. CONCLUSION: We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd-cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd-cfDNA testing into clinical practice are needed.

Early experience and recommendations for the use of an automated estimator of solution volume for negative pressure wound therapy with instillation.

INTRODUCTION: NPWTi is a device that combines the benefits of traditional NPWT with periodic irrigation. This automated device allows for preprogrammed cycles of dwelling of a solution and negative pressure onto the wound surface. Its adoption has been hampered by the perceived difficulty of estimating the volume of solution needed per dwell cycle. A new software update includes an AESV that makes this determination for the clinician. OBJECTIVE: This case series of 23 patients presents the observations of 3 experienced users at 3 institutions who employed NPWTi with the AESV. MATERIALS AND METHODS: The authors subjectively assessed the wounds to determine whether the expected clinical result was achieved utilizing AESV on a variety of anatomical locations and wound types. RESULTS: The AESV demonstrated the ability to reliably estimate adequate solution amount in 65% (15/23) of cases. In wounds greater than 120 cm3, the AESV underestimated the amount of solution needed. CONCLUSION: To the authors' knowledge, this is the first publication describing the use of AESV for NPWTi. The benefits and limitations of this software upgrade are reported and recommendations for optimal use are provided.

Neither Antiplatelet nor Anticoagulant Therapy Increases Graft Failure after Split-thickness Skin Grafting.

Split-thickness skin grafts (STSG) are an effective modality for lower extremity wound coverage. Many patients in the highly comorbid chronic wound population present with cardiovascular disease requiring chronic antiplatelet or anticoagulant therapy, theoretically increasing risk for bleeding complications, donor site morbidity, and poor graft take. Some surgeons advocate temporary cessation of antithrombotic therapy, which may increase cardiovascular risk. The objective of this study was to examine the effects of anticoagulation use on STSG outcomes. Methods: All patients receiving STSGs for lower extremity wounds from 2014 to 2016 at a single institution were retrospectively reviewed. Successful grafts were defined as greater than 99.5% wound coverage. Patients were divided into two groups: anticoagulation/antiplatelet or no anticoagulation/antiplatelet. Continuous variables were described by means and SDs and analyzed using student's t-test. Categorical variables were described by frequencies and percentages and analyzed using Chi-square or Fisher exact tests as appropriate. Results: In total, 231 wounds were identified among 189 patients; 124 patients were receiving at least one antiplatelet/anticoagulant at time of grafting. Three hematomas were reported during 30 days of follow-up; there was no significant difference between groups (P > 0.05). Anticoagulation/antiplatelet therapy in the perioperative period had no significant impact on STSG take and overall healing. Conclusions: The findings from this study demonstrate that administration of anticoagulant/antiplatelet agents in the perioperative period does not increase the risk of skin graft failure. Based on these findings, STSG can be performed without cessation of anticoagulation or antiplatelet therapy.

Sex dependent differences of temporomandibular condylar bone mineral density distribution.

OBJECTIVE: The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. METHODS: CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. RESULTS: The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. CONCLUSION: Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

Immunodominant MHC-II (Major Histocompatibility Complex II) Restricted Epitopes in Human Apolipoprotein B.

BACKGROUND: CD (cluster of differentiation) 4+ T-cell responses to APOB (apolipoprotein B) are well characterized in atherosclerotic mice and detectable in humans. CD4+ T cells recognize antigenic peptides displayed on highly polymorphic HLA (human leukocyte antigen)-II. Immunogenicity of individual APOB peptides is largely unknown in humans. Only 1 HLA-II-restricted epitope was validated using the DRB1*07:01-APOB3036-3050 tetramer. We hypothesized that human APOB may contain discrete immunodominant CD4+ T-cell epitopes that trigger atherosclerosis-related autoimmune responses in donors with diverse HLA alleles. METHODS: We selected 20 APOB-derived peptides (APOB20) from an in silico screen and experimentally validated binding to the most commonly occurring human HLA-II alleles. We optimized a restimulation-based workflow to evaluate antigenicity of multiple candidate peptides in HLA-typed donors. This included activation-induced marker assay, intracellular cytokine staining, IFNγ (interferon gamma) enzyme-linked immunospot and cytometric bead array. High-throughput sequencing revealed TCR (T-cell receptor) clonalities of APOB-reactive CD4+ T cells. RESULTS: Using stringent positive, negative, and crossover stimulation controls, we confirmed specificity of expansion-based protocols to detect CD4+ T cytokine responses to the APOB20 pool. Ex vivo assessment of AIM+CD4+ T cells revealed a statistically significant autoimmune response to APOB20 but not to a ubiquitously expressed negative control protein, actin. Resolution of CD4+ T responses to the level of individual peptides using IFNγ enzyme-linked immunospot led to the discovery of 6 immunodominant epitopes (APOB6) that triggered robust CD4+ T activation in most donors. APOB6-specific responding CD4+ T cells were enriched in unique expanded TCR clonotypes and preferentially expressed memory markers. Cytometric bead array analysis detected APOB6-induced secretion of both proinflammatory and regulatory cytokines. In clinical samples from patients with angiographically verified coronary artery disease, APOB6 stimulation induced higher activation and memory phenotypes and augmented secretion of proinflammatory cytokines TNF (tumor necrosis factor) and IFNγ, compared with patients with low coronary artery disease. CONCLUSIONS: Using 3 cohorts, each with ≈20 donors, we discovered and validated 6 immunodominant, HLA-II-restricted APOB epitopes. The immune response to these APOB epitopes correlated with coronary artery disease severity.

A novel donor-derived cell-free DNA assay for the detection of acute rejection in heart transplantation.

BACKGROUND: Endomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients. METHODS: Plasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures. RESULTS: A total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pc < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction ≥0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples. CONCLUSIONS: This novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients.

Risks Factors Associated With Major Lower Extremity Amputation After Vertical Contour Calcanectomy.

The primary aim of the study is to determine risks for major lower extremity amputation after undergoing Vertical Contour Calcanectomy. Subanalysis was performed comparing patients who underwent Vertical Contour Calcanectomy who were fully ambulatory to those who were partially or nonambulatory postoperatively. Within the cohort of 63 patients included in the Vertical Contour Calcanectomy 85.71% (54/63) of patients had diabetes mellitus, 53.97% (34/63) had peripheral arterial disease, and 19.05% (12/63) had Charcot Neuroarthropathy. Multivariate logistic regression, found that (1) patients that underwent primary closure at the time of the Vertical Contour Calcanectomy, were 79.9% more likely (odds ratio [OR] 0.20; 95% confidence interval [CI] 0.04-0.96) to have limb salvage and that (2) female patients were 85.4% less likely compared to male patients (OR 0.15; 95% CI 0.02-0.99) to undergo major lower extremity amputation. Patients with coronary artery disease were 5.2 times more likely (OR 5.18; 95% CI 1.120-23.94) and patients that were nonambulatory preoperatively, were 10.3 times more likely (OR 10.28; 95% CI 1.60-66.26), to be partially or nonambulatory after Vertical Contour Calcanectomy. Primary closure at time of Vertical Contour Calcanectomy significantly decreases the risk of major lower extremity amputation, and diminished preoperative ambulatory status as well as coronary artery disease makes it less likely that patients return to full ambulation after Vertical Contour Calcanectomy.

Double Versus Triple Arthrodesis Fusion Rates: A Systematic Review.

Hindfoot arthrodesis is often required for end-staged deformities, such as posterior tibial tendon dysfunction, osteoarthritis, or rheumatoid arthritis. Although the need for hindfoot arthrodesis is generally accepted in severe deformities, there is a debate whether a double or triple arthrodesis should be performed. The aim of our systematic review is to review the fusion rates and mean time to fusion in double and triple arthrodesis. A total of 184 articles were identified using the keyword search through the database of articles published from 2005 to 2017. After review by 3 physicians, a total of 13 articles met the eligibility criteria. The reason for double or triple arthrodesis within the studies were posterior tibial tendon dysfunction, tarsal coalition, degenerative joint disease, osteoarthritis, rheumatoid arthritis, Charcot Marie Tooth, Multiple Sclerosis, Polio, neuromuscular disorder, cerebral palsy, acrodystrophic neuropathy, clubfoot, post-traumatic, and seronegative arthropathy (spondyloarthritis). Within these 13 studies, there were a total of 343 (6-95) subjects extremities operated on. The overall fusion rate for double arthrodesis was 91.75% (289/315) compared to 92.86% (26/28) triple arthrodesis fusion rate, p value .8370. The mean time to fusion for double arthrodesis was 17.96 ± 7.96 weeks compared to 16.70 ± 8.18 weeks for triple arthrodesis, p value = .8133. There are risks associated with triple arthrodesis including increased surgical times, lateral wound complications, residual deformity, surgical costs and peri-articular arthritis. Given the benefits of double arthrodesis over triple arthrodesis and the nearly equivalent fusion rates and time to fusion, double arthrodesis is an effective alternative to triple arthrodesis. The authors of this systematic review recommend double arthrodesis as the hindfoot fusion procedure of choice.