Tibial Component Subsidence in a Total Ankle System Comparing Standard Technique Versus a Hybrid Technique.

Total ankle arthroplasty (TAA) is a viable treatment option for end-stage ankle arthritis. However, implant survivorship remains an important consideration. Concerns regarding early component loosening with the low-profile tibial tray utilized by fourth-generation TAA systems have been raised in the literature. We have previously described our preliminary outcomes of a hybrid technique combining a stemmed intramedullary tibial component with a chamfer-cut talar component for TAA. A retrospective study comparing short-term outcomes of the tibial component between a standard fourth-generation TAA system versus our hybrid technique was performed. 46 patients with a minimum of 1-year follow up were included in the analyses. There were 25 subjects in the standard implant cohort utilizing a low-profile tibial tray, and 21 subjects in the hybrid group utilizing a stemmed intramedullary tibial component. No statistically significant difference between the demographics of each group was found. The rate of tibial component subsidence was 8% (n = 2) in the standard implant group, and 0% (n = 0) in the hybrid group, though this did not meet statistical significance (p = .49). Mean time to subsidence was 6 months, and revision rate due to tibial component subsidence was 2.1% (n = 1). Periprosthetic lucency was present on most recent follow-up radiographs in 32% and 9.5% of ankles in the standard and hybrid groups, respectively (p = .08). Despite prior concerns for tibial component subsidence with the standard fourth-generation system, we demonstrated low rates in both implant groups. Additional studies are needed to further explore factors that may predispose patients to early tibial component subsidence and resulting implant failure.

Time to Revision After Periprosthetic Joint Infection in Total Ankle Arthroplasty: A Systematic Review.

While not a common complication after total ankle arthroplasty (TAA), periprosthetic joint infection (PJI) presents a significant risk of implant failure. The primary aim of this systematic review was to evaluate time to revision after PJI in patients who had undergone TAA. An extensive search strategy via electronic databases initially captured 11,608 citations that were evaluated for relevance. Ultimately, 12 unique articles studying 3040 implants met inclusion criteria. The time to revision surgery due to PJI was recorded for each study and a weighted average obtained. The prevalence of PJI was 1.12% (n = 34). We found that the average time to revision due to PJI was 30.7 months, or approximately 2.6 years after the index TAA procedure. By literature definitions, the majority of cases (91.2%, n = 31) were beyond the "acute" PJI phase. The population was divided into 2 groups for further analysis of chronic infections. PJIs before the median were classified as "early" and those after as "late" chronic. The majority of cases (61.8%) were late chronic with an average time to revision of 44.3 months. A smaller number were early chronic (29.4%) with revision within 10.8 months. After summarizing the rates of infection and times to revision reported in the literature, we suggest modifying the current PJI classification to include early chronic and late chronic subgroups so that the total ankle surgeon is better prepared to prudently diagnose and treat PJIs.

Preliminary Report of a Hybrid Total Ankle Arthroplasty Combining a Stemmed Intramedullary Tibial Component With Chamfer-Cut Talar Dome.

Total ankle arthroplasty (TAA) is a viable treatment for end-stage ankle arthritis. In our experience, a stemmed intramedullary tibial component combined with a chamfer-cut talar component provides the most stable construct for TAA. We present our technique for placement of this hybrid prosthesis utilizing the INBONE tibial component in combination with the INFINITY talar component. This technique differs from the standard protocol by minimizing use of both patient-specific and standard intraoperative guides. The primary aim of this study is to report our preliminary outcomes with our novel technique. Secondarily, we aim to demonstrate that placement of this hybrid prosthesis is radiographically reproducible and accurate. The first 10 patients undergoing this technique with at least 1 year of follow-up were retrospectively reviewed. Average visual analog pain scale decreased from 7.4 preoperatively to 0.5 at 1 year postoperatively. The average time to weightbearing was 6.4 weeks. Complications were minimal, and no implant-related complications were encountered. First weightbearing ankle radiographs postoperatively were evaluated by 3 reviewers to determine accuracy of the tibial intramedullary stem in relation to the anatomical axis of the tibia. We found that the deviation of the tibial implant from the anatomic axis was on average 0.9°± 0.5° in the coronal plane, and 2.2°± 2.7° in the sagittal plane. Inter-rater reliability was 83%. We conclude that this hybrid technique utilizing a stemmed intramedullary tibial component in combination with a chamfer-cut talar component for TAA is reproducible, accurate, and safe.

Total Ankle Arthroplasty Survivorship: A Meta-analysis.

The gold standard for management of end-stage ankle arthritis was previously ankle arthrodesis; however, improvements in total ankle replacements are making this a more viable treatment option. The primary aim of this meta-analysis was to evaluate the survivorship of total ankle replacement implants currently in use. An extensive search strategy initially captured 20,842 citations that were evaluated for relevance. Abstract screening produced 97 articles to be read in entirety, of which 10 articles studying 1963 implants met all prospective inclusion criteria for analysis. Overall survivorship of all implants was 93.0% (95% confidence interval, 85.2-96.9) using a random effect model. There was significant heterogeneity between the studies (Q = 131.504). Meta-regression identified an inverse relationship between survivorship and study follow-up duration (p < .0001). Furthermore, age (p = .36) and implant type (fixed-bearing [95.6%, 95% confidence interval, 85.9-98.7] versus mobile-bearing ]89.4%, 95% confidence interval, 79.6%-94.8%]) did not have a statistically significant impact on survivorship, p = .213. However, patients with higher preoperative functional scores had improved survivorship (p = .001). Complications were inconsistently reported with varied definitions. In order of reported frequency, complications were classified into technical error (28.15%), subsidence (16.89%), implant failure (13.28%), aseptic loosening (6.3%), intraoperative fracture (5.67%), wound problems (4.3%), deep infection (1%), and postoperative fracture (0.0001%). Overall study quality was low, with only 10% being prospective and 90% from nonregistry data. The results from this meta-analysis revealed a promising overall survivorship of current implants in use for total ankle replacement; however higher quality studies with standardized outcomes measures are needed.

Quantitative activation suppression assay to evaluate human bone marrow-derived mesenchymal stromal cell potency.

BACKGROUND AIMS: With the increasing use of cell therapies involving immune modulatory cells, there is a need for a simple standardized method to evaluate and compare the suppressive potency of different cell products. We used the Karpas 299 (K299) cell line as the reference suppressor cell to develop a standardized suppression assay to quantify the immune-modulatory capacity of bone marrow-derived mesenchymal stromal cells (BM-MSCs). METHODS: Healthy donor CD4 T cells were co-cultured with the K299 cell line or with third-party BM-MSCs. After stimulation with anti-CD3/CD28 beads, CD154 activation and proliferation of CD4 T cells were measured to calculate suppression. RESULTS: The K299 cell line reproducibly suppressed both the activation and proliferation of healthy donor CD4 T cells in a dose-dependent manner. A rapid (16-h) assay that was based on activation-suppression was selected for development. In replicate testing, there was an inherent variability of suppression of 11% coefficient of variation between different responder T cells. Suppression by BM-MSCs on different responders correlated with suppression by K299. We therefore used K299 suppression as the reference to define suppression potency of BM-MSCs in K299 Suppression Units. We found that inter-donor variability, passage number, method of manufacture and exposure of BM-MSCs to steroids or interferon-γ all affected BM-MSC potency of suppression. CONCLUSIONS: This method provides a platform for standardizing suppressor function to facilitate comparisons between laboratories and for use as a cell product release assay.

Genetically engineered fixed K562 cells: potent "off-the-shelf" antigen-presenting cells for generating virus-specific T cells.

BACKGROUND AIMS: The human leukemia cell line K562 represents an attractive platform for creating artificial antigen-presenting cells (aAPC). It is readily expandable, does not express human leukocyte antigen (HLA) class I and II and can be stably transduced with various genes. METHODS: In order to generate cytomegalovirus (CMV) antigen-specific T cells for adoptive immunotherapy, we transduced K562 with HLA-A∗0201 in combination with co-stimulatory molecules. RESULTS: In preliminary experiments, irradiated K562 expressing HLA-A∗0201 and 4-1BBL pulsed with CMV pp65 and IE-1 peptide libraries failed to elicit antigen-specific CD8⁺ T cells in HLA-A∗0201⁺ peripheral blood mononuclear cells (PBMC) or isolated T cells. Both wild-type K562 and aAPC strongly inhibited T cell proliferation to the bacterial superantigen staphylococcal enterotoxin B (SEB) and OKT3 and in mixed lymphocyte reaction (MLR). Transwell experiments suggested that suppression was mediated by a soluble factor; however, MLR inhibition was not reversed using transforming growth factor-ß blocking antibody or prostaglandin E2 inhibitors. Full abrogation of the suppressive activity of K562 on MLR, SEB and OKT3 stimulation was only achieved by brief fixation with 0.1% formaldehyde. Fixed, pp65 and IE-1 peptide-loaded aAPC induced robust expansion of CMV-specific T cells. CONCLUSIONS: Fixed gene-modified K562 can serve as effective aAPC to expand CMV-specific cytotoxic T lymphocytes for therapeutic use in patients after stem cell transplantation. Our findings have implications for broader understanding of the immune evasion mechanisms used by leukemia and other tumors.

The Role of Arthroscopy After Total Ankle Replacement.

Alongside advances and trends in foot and ankle surgery, arthroscopy provides a minimally invasive option in exploring and addressing pain after total ankle replacement (TAR). It is not uncommon for patients to develop pain months or even years after TAR implantation for both fixed and mobile-bearing designs. Arthroscopic debridement of gutter pain can provide successful outcomes in the hands of the experienced arthroscopist. Surgeon preference and experience will dictate the threshold for intervention, approach, and tool selection. This article provides a brief look into the background, indications, technique, limitations, and outcomes for arthroscopy after TAR.

The effect of a silver hydrogel sheet dressing on postsurgical incision healing after foot and ankle surgery.

Introduction: Silver hydrogel dressings are antimicrobial dressings with the potential to aid post-surgical healing. The purpose of this study is to evaluate the effects of a silver hydrogel dressing on postoperative scarring and complications. Methods: 40 foot and ankle patients (48.43 ± 16.82 years) were included in the study with 20 patients in each group. Postoperatively, the treatment group was treated with a silver hydrogel sheet dressing, and the control group was treated with a standard petroleum-based dressing. Follow-up was performed at two, six, and 12 weeks. Postoperative scarring and complications were evaluated and compared between groups. Scarring was evaluated using the Patient and Observer Scar Assessment Scale (POSAS). Scar length and width were measured using digital calipers and used to compute scar area. Results: The treatment group demonstrated statistically significant improvements in the POSAS observer score and observer opinion at six and 12 weeks (p < 0.001). Additionally, patient reported pain was significantly lower for the treatment group than the control group at 12 weeks (p < 0.001). Patient reported itch declined across time for both groups (p < 0.001) with significantly less itching reported by the treatment group (p = 0.027). Scar area was also significantly lower for the treatment group than the control group at six weeks and 12 weeks (p ≤ 0.002). Neither group experienced any postoperative complications. Conclusion: These results suggest that the inherent properties of the silver hydrogel dressing may improve postsurgical scarring. Lay Summary: Surgical incisions result in scar, which can present both cosmetic and rehabilitation concerns after foot or ankle surgery. It is standard to use a petroleum-based dressing on incisions after surgery, however, advancements in incisional dressings have been made over the past 20 years. One such advancement is silver-impregnated hydrogel sheet dressings which have been shown to maintain a moist wound environment conducive to healing, while decreasing the chance of infection through its antimicrobial properties. This paper evaluates scar healing after foot or ankle surgery in patients treated with either the standard petroleum-based dressing, or the silver hydrogel sheet dressing. Patients who were treated with the silver hydrogel dressing had less itching and pain, as well as a smaller scar area than patients in the standard dressing group. Therefore, our results suggest that the silver hydrogel dressing may improve scarring after surgery.

Perceptions of the Podiatric Medicine Profession: A Survey of Medical Students in Philadelphia, Pennsylvania.

BACKGROUND: Medical students (MSs) in allopathic and osteopathic medical programs may not be adequately exposed to the role of podiatric physicians and surgeons in health care. We explored perceptions of the specialty field of podiatric medicine from the perspective of MSs in the Philadelphia, Pennsylvania, area. METHODS: In this cross-sectional survey study, responses regarding podiatric education and scope of practice were collected via a 16-question, self-reported, anonymous online survey distributed to MSs at one osteopathic and three allopathic medical schools in the Philadelphia area. Inferences and conclusions were drawn from the percentages of respondents. Statistical analyses for school of attendance, year of study, and physician relative subgroups were performed. RESULTS: The 129 survey responses obtained revealed misunderstandings regarding podiatric education and training. Only 45.7% correctly answered that podiatric medical students do not take the United States Medical Licensing Examination. The results also showed the perception of podiatry in a positive light, with approximately 80% of respondents agreeing that the term doctor is applicable when referring to a podiatrist. Respondents with a physician relative were more likely to rate podiatry's role in health care higher on a scale from 0 (inessential) to 5 (equivalent to MDs/DOs) than those without a physician relative. CONCLUSIONS: The results of this preliminary survey were generally positive and optimistic while also identifying some misconceptions regarding MS perceptions of podiatric medical training and scope of practice. Further studies are needed to evaluate perceptions of podiatry from the perspective of other members of the health-care team to improve interprofessional relations and understanding.

Long term maintenance of myeloid leukemic stem cells cultured with unrelated human mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs) support the growth and differentiation of normal hematopoietic stem cells (HSCs). Here we studied the ability of MSCs to support the growth and survival of leukemic stem cells (LSCs) in vitro. Primary leukemic blasts isolated from the peripheral blood of 8 patients with acute myeloid leukemia (AML) were co-cultured with equal numbers of irradiated MSCs derived from unrelated donor bone marrow, with or without cytokines for up to 6weeks. Four samples showed CD34(+)CD38(-) predominance, and four were predominantly CD34(+)CD38(+). CD34(+) CD38(-) predominant leukemia cells maintained the CD34(+) CD38(-) phenotype and were viable for 6weeks when co-cultured with MSCs compared to co-cultures with cytokines or medium only, which showed rapid differentiation and loss of the LSC phenotype. In contrast, CD34(+) CD38(+) predominant leukemic cells maintained the CD34(+)CD38(+) phenotype when co-cultured with MSCs alone, but no culture conditions supported survival beyond 4weeks. Cell cycle analysis showed that MSCs maintained a higher proportion of CD34(+) blasts in G0 than leukemic cells cultured with cytokines. AML blasts maintained in culture with MSCs for up to 6weeks engrafted NSG mice with the same efficiency as their non-cultured counterparts, and the original karyotype persisted after co-culture. Chemosensitivity and transwell assays suggest that MSCs provide pro-survival benefits to leukemic blasts through cell-cell contact. We conclude that MSCs support long-term maintenance of LSCs in vitro. This simple and inexpensive approach will facilitate basic investigation of LSCs and enable screening of novel therapeutic agents targeting LSCs.

Oral Immunoglobulin Levels are Not a Good Surrogate for Cervical Immunoglobulin Levels.

BACKGROUND: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig) levels. To do so, we examined (1) whether oral IgG and IgA levels correlated with those observed at the cervix, and (2) whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. METHODS: We obtained oral samples from a group of 85 Costa Rican woman 25-35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. RESULTS: We did not observe an association between oral and cervical IgG [linear regression coefficient (LRC) 0.01; 95% CI, -0.05 to 0.07] and IgA levels (LRC 0.02; 95% CI, -0.04 to 0.08). Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. CONCLUSION: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites.