Comparison of Minimally Invasive Chevron Akin and Open Lapidus Surgery in Older Patients at a Minimum 1-Year Follow-Up.

Background: Hallux valgus deformity affects more than 35% of people aged ≥65 years. Surgical correction in this population can be more complicated because of poor bone quality, worse deformity, and postoperative recovery challenges. The purpose of this study was to compare the radiographic and clinical outcomes of patients aged ≥65 years who underwent either open Lapidus or minimally invasive chevron Akin osteotomy for bunion correction. Methods: A retrospective review identified 62 patients aged ≥65 years who were treated surgically for hallux valgus with at least 1-year postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores (physical function and pain interference). Preoperative and at least 6-month postoperative radiographs were measured for the hallux valgus angle and intermetatarsal angle. PROMIS scores were obtained preoperatively and at 1 and/or 2 years postoperatively. Differences in demographic, clinical, and radiographic outcomes were assessed using the Mann Whitney U test and P values were adjusted for a false discovery rate of 5%. Results: There was no difference between the MIS and open cohorts in pre- or postoperative radiographic measurements or clinical outcomes at any time point. At 1 year postoperatively, both groups had statistically significant improvements in the PROMIS pain interference domain but only the MIS group had a statistically significant improvement in the PROMIS physical function domain. Clinical significance was equivocal. At 2 years postoperatively, there were clinically and statistically significant improvements in the PROMIS pain interference and physical function domains for the open and MIS groups. Conclusion: Patients in both surgical groups had improvement in radiographic measurements and 2-year PROMIS scores, although there was no clinical or statistical difference found between groups. MIS and open surgical techniques appear to be safe and effective in correcting hallux valgus in older patients; however, patients may need to be counseled that maximum improvement after surgery may take more than 1 year. Level of Evidence: Level III, retrospective cohort study.

Bile Acids in Pancreatic Carcinogenesis.

Pancreatic cancer (PC) is a dangerous digestive tract tumor that is becoming increasingly common and fatal. The most common form of PC is pancreatic ductal adenocarcinoma (PDAC). Bile acids (BAs) are closely linked to the growth and progression of PC. They can change the intestinal flora, increasing intestinal permeability and allowing gut microbes to enter the bloodstream, leading to chronic inflammation. High dietary lipids can increase BA secretion into the duodenum and fecal BA levels. BAs can cause genetic mutations, mitochondrial dysfunction, abnormal activation of intracellular trypsin, cytoskeletal damage, activation of NF-κB, acute pancreatitis, cell injury, and cell necrosis. They can act on different types of pancreatic cells and receptors, altering Ca2+ and iron levels, and related signals. Elevated levels of Ca2+ and iron are associated with cell necrosis and ferroptosis. Bile reflux into the pancreatic ducts can speed up the kinetics of epithelial cells, promoting the development of pancreatic intraductal papillary carcinoma. BAs can cause the enormous secretion of Glucagon-like peptide-1 (GLP-1), leading to the proliferation of pancreatic ß-cells. Using Glucagon-like peptide-1 receptor agonist (GLP-1RA) increases the risk of pancreatitis and PC. Therefore, our objective was to explore various studies and thoroughly examine the role of BAs in PC.

Correlation of Clinical Outcomes and Relative Position of the First Metatarsal After the Modified Lapidus Procedure.

BACKGROUND: Hallux valgus is a complex 3-dimensional deformity, and the modified Lapidus is a commonly used procedure to correct moderate to severe cases. Shortening and elevation of the first ray can occur with this procedure, which may result in increased pressure on the lesser metatarsal heads. However, there is currently no consensus regarding an accepted length and elevation of the first ray following the modified Lapidus. Therefore, the purpose of this study is to evaluate the impact of the position of the first ray on patient-reported outcome measures. METHODS: This retrospective study identified 68 patients (72 feet) who underwent the modified Lapidus bunionectomy over a 4-year period at a single institution with a median follow-up of 24 months (range, 11-35.6 months). Patients were included if they were over 18 years of age, had pre- and postoperative weightbearing computed tomography (WBCT) scans, and preoperative and minimum 1-year postoperative Patient-Reported Outcome Measurement Information System (PROMIS) scores. PROMIS scores from 6 domains including physical function, pain interference, pain intensity, global physical health, global mental health, and depression were evaluated and compared pre- and postoperatively. Radiographic parameters were measured and compared before and after surgery. Paired t tests were used to evaluate the significance of pre- to postoperative changes. Differences between cohorts were compared using Mann-Whitney U test for continuous variables or Fisher exact test for categorical variables. Correlation between radiographic measurements and patient-reported outcomes were assessed using the Spearman rank rho estimate and visualized with scatterplots with a linear regression. RESULTS: PROMIS physical function, pain interference, pain intensity, and global physical health improved significantly following the modified Lapidus (all P < .001); however, scores did not show any significant correlation with shortening of the first ray up to a maximum shortening of 4.8 mm. The length of the first metatarsal relative to the second decreased by an average of 2.7 mm following the procedure when measured on WBCT (P < .001), and 2.6 mm when measured on plain radiographs (P < .001). No significant elevation of the first ray was observed postoperatively. CONCLUSION: This study revealed that the Lapidus bunionectomy resulted in significantly improved pain and physical function at short-term follow-up. The amount of first ray shortening and elevation that occurred in this cohort did not adversely affect patient-reported outcomes.

Preoperative Degenerative Changes at the Tibial Sesamoid-Metatarsal Joint in Hallux Valgus: Association With Postoperative Patient-Reported Outcomes After Modified Lapidus Procedure.

Background: Degenerative changes at the sesamoid-metatarsal joints (SMJs) may be a source of pain following hallux valgus surgery. The aims of this study were to describe degenerative changes at the SMJs on weightbearing computed tomography (WBCT) scans and, secondarily, investigate their association with 1-year patient-reported outcome scores following a modified Lapidus procedure for hallux valgus. We hypothesized that reduced joint space in the SMJs would correlate with worse patient-reported outcomes. Methods: Fifty-seven hallux valgus patients who underwent a modified Lapidus procedure had preoperative and minimum 5-month postoperative WBCT scans, and preoperative and at least 1-year postoperative PROMIS physical function (PF), pain interference, and pain intensity scores were included. Degenerative changes at the SMJs were measured using distance mapping between the sesamoids and first metatarsal head on preoperative and postoperative WBCT scans. The minimum and average distances between the first metatarsal head and tibial sesamoid (tibial-SMJ) for each patient preoperatively and postoperatively were measured. Sesamoid station was measured on WBCT scans using a 0 to 3 grading system. Linear regression was used to investigate the correlations between minimum preoperative and postoperative tibial-SMJ distances and 1-year postoperative PROMIS scores. Results: The median minimum and average tibial-SMJ distances increased from 0.82 mm (interquartile range [IQR] 0.40-1.03 mm) and 1.62 mm (IQR 1.37-1.75 mm) preoperative to 1.09 mm (IQR 0.96-1.23 mm) and 1.73 mm (IQR 1.60-1.91 mm) postoperative (P < .001 and P < .001), respectively. In a subset of patients with complete sesamoid reduction, we found an association between preoperative minimum tibial-SMJ distance and 1-year postoperative PROMIS PF scores (coefficient 7.2, P = .02). Conclusion: Following the modified Lapidus procedure, there was a statistically significant increase in the tibial-SMJ distance. Additionally, in patients with reduced sesamoids postoperatively, reduced preoperative tibial-SMJ distance correlated with worse PROMIS PF scores. Level of Evidence: Level IV, case series.

Defining the Patient Acceptable Symptom State (PASS) for PROMIS After Total Ankle Replacement.

BACKGROUND: Although patient-reported outcomes (PROs), such as the Patient-Reported Outcomes Measurement Information System (PROMIS), are a key element of evaluating success after total ankle replacement (TAR), many do not explicitly state a key factor of postoperative success: is the patient satisfied with their outcome after TAR? The patient acceptable symptom state (PASS) represents the symptom threshold beyond which patients consider themselves well. This study aimed to establish the PROMIS thresholds for the PASS in a primary cohort of TAR patients. METHODS: This single-institution study included 127 primary TAR patients with preoperative and 2-year postoperative PROMIS scores. At 2 years postoperatively, patients answered 2 PASS anchor questions (Satisfaction, Delighted-Terrible scale) with Likert-scale responses. PASS thresholds with 95% confidence intervals (CIs) were calculated from PROMIS scores using an anchor-based method. Using a bootstrapping technique with 1,000 iterations, the Youden index was calculated to determine the best specificity and sensitivity coordinates to maximize their combination. Finally, preoperative variables associated with the likelihood of achieving the PASS were assessed. RESULTS: There was a strong association between PASS thresholds and PROMIS domains, especially Pain Interference (PASS threshold of <56.0, area under the receiver operating characteristic curve [AUC] = 0.940), Pain Intensity (<48.4, AUC = 0.936), and Physical Function (>44.7, AUC = 0.883). The likelihood of achieving the PASS was not affected by age, race, gender, American Society of Anesthesiologists (ASA) class, body mass index, or severity of ankle deformity. Patients with worse preoperative Physical Function and Global Mental Health scores were less likely to meet the PASS threshold for Physical Function postoperatively (p = 0.028 and 0.041). CONCLUSIONS: The ability to reach the PASS after TAR was most strongly associated with postoperative PROMIS pain scores. However, PASS thresholds were generally poorer than population means. This demonstrates that patients do not need to reach normal pain or physical function levels to have an acceptable symptom state after TAR. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Defining the patient acceptable symptom state using PROMIS following reconstruction of the progressive collapsing foot deformity.

BACKGROUND: The patient acceptable symptom state (PASS) represents the threshold beyond which patients are satisfied with their outcome. This study aimed to define PASS thresholds for progressive collapsing foot deformity (PCFD) reconstruction using Patient-Reported Outcomes Measurement Information System (PROMIS) scores and anchor question responses. METHODS: This retrospective study consisted of 109 patients who underwent flexible PCFD reconstruction, had preoperative and 2-year postoperative PROMIS scores, and 2-year postoperative anchor question responses. ROC curve analyses were performed to quantify PASS thresholds. RESULTS: PASS thresholds for the PROMIS Physical Function (PF) and Pain Interference (PI) domains were found to be lower and higher, respectively, than population norms. Furthermore, patients with higher preoperative PROMIS PF scores or lower preoperative PROMIS PI scores had a significantly higher likelihood of achieving the PASS thresholds. CONCLUSION: In addition to guiding future outcomes research, these results may help surgeons optimize treatment for PCFD and better manage patient expectations. LEVEL OF EVIDENCE: III, retrospective cohort study.

Passive Eversion Assessment for Progressive Collapsing Foot Deformity After Lateral Column Lengthening: A Cadaveric Biomechanical Study.

BACKGROUND: Reduced hindfoot eversion motion has been proposed as a cause of increased lateral foot pressure following lateral column lengthening (LCL) for progressive collapsing foot deformity (PCFD). A subjective intraoperative assessment of passive eversion has been suggested to help evaluate correction; however, it is unclear how passive eversion correlates with objective measurements of foot stiffness. Our objectives were to quantify the relationship between the maximum passive eversion in hindfoot joints following LCL with plantar pressure during stance and to determine the influence of wedge size on these outcomes. METHODS: Ten cadaveric specimens extending from the mid-tibia distally were tested on a 6-degrees-of-freedom robot to simulate the stance phase of level walking. Five conditions were tested: intact, simulated PCFD, and 3 LCL wedge conditions (4, 6, and 8 mm). Outcomes included the lateral-to-medial forefoot plantar pressure (LM) ratio during stance and the maximum passive eversion measured in the hindfoot joints. Simple linear regressions were performed to evaluate relationships between outcomes and wedge sizes. RESULTS: A strong negative relationship was found between passive subtalar eversion and the LM ratio during stance (r[38] = -0.46; p = 0.0007), but not between passive talonavicular eversion and the LM ratio (r[38] = -0.02; p = 0.37). Wedge size was strongly related to subtalar eversion (r[38] = -0.77; p < 0.0001), talonavicular eversion (r[38] = -0.55; p = 0.0003), and the LM ratio (r[38] = 0.70; p < 0.0001). Increased wedge size resulted in average decreases in subtalar and talonavicular eversion of 1.0° (95% confidence interval [CI]: 0.8° to 1.3°) and 1.2° (95% CI: 0.6° to 1.6°), respectively. Increased wedge size also increased the LM ratio by 0.38 (95% CI: 0.25 to 0.50), indicating a lateral shift in plantar pressure. CONCLUSIONS: Decreased hindfoot eversion following LCL was related to increased lateral plantar pressure during stance. Increasing wedge size correlated with decreasing passive hindfoot eversion and increasing lateral plantar pressure, suggesting that intraoperative preservation of eversion motion may be important for preventing excessive lateral loading. CLINICAL RELEVANCE: To avoid overcorrection or undercorrection of the deformity, hindfoot eversion assessment in addition to radiographic evaluation may be important for optimizing the amount of lengthening to achieve successful LCL.

Implant Choice May Reduce the Risk of Early Mechanical Failure in Total Ankle Replacement.

BACKGROUND: Total ankle replacements (TARs) have rapidly advanced in terms of volume, technique, design, and indications. However, TARs are still at risk for early mechanical failure and revision. Prior studies have investigated potential risk factors for failure, but have been limited to smaller series or older implants. This study sought to identify risk factors for early mechanical failure in modern TAR. METHODS: This is a retrospective study of a single-institution registry. Five surgeons contributed cases involving patients who underwent a primary TAR with any implant. Implants were grouped on the basis of the type of fixation. The primary outcome was early mechanical failure (revision with component removal for a non-infectious etiology, that is, subsidence, aseptic loosening, and/or malalignment). Logistic regression determined the effects of age, weight, hindfoot arthrodesis, implant type, and radiographic deformity on failure. RESULTS: The 731 included patients had a mean follow-up of 2.7 years. Ten percent (71 patients) had hindfoot arthrodesis. There were 33 mechanical failures (4.5%) at a mean of 1.7 years after the index surgical procedure. Our model demonstrated that hindfoot arthrodesis was associated with 2.7 times greater odds of failure (p = 0.045), every 10 kg of body weight increased the odds of tibial-sided failure by 1.29 times (p = 0.039), and implants with more extensive tibial fixation (stems or keels) lowered the odds of tibial failure by 95% (p = 0.031). CONCLUSIONS: In patients with uncontrollable risk factors (hindfoot arthrodesis) or risk factors that may or may not be modifiable by the patient (weight), implants with more robust tibial fixation may be able to reduce the risk of early mechanical failure. Further research is warranted to support efforts to decrease early failure in TAR. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Discrepancies Between Intraoperative and Postoperative Ankle Motion Measured for Anterior-Approach Total Ankle Arthroplasty.

BACKGROUND: Although intraoperative ankle motion serves as a foundational reference for anticipated motion after surgery and guides the addition of procedures to enhance ankle motion in total ankle arthroplasty (TAA), the relationship between intraoperative and postoperative ankle motion remains unclear. This study aimed to investigate the discrepancy between intraoperative and postoperative ankle range of motion (ROM) following TAAs using the anterior-approach, fixed-bearing systems. METHODS: This study retrospectively reviewed 67 patients (67 ankles) who underwent primary TAA at a single institution. Three different types of anterior-approach, fixed-bearing TAA systems were included. Intraoperative fluoroscopy was used to document the maximal dorsiflexion and plantar flexion at the end of the case. Standardized weightbearing maximum dorsiflexion and plantar flexion sagittal radiographs were obtained pre- and postoperatively, following a previously described method. The motion between 3 different time points (preoperative, intraoperative, and postoperative [mean 11.4 months]) was compared using pairwise t tests, and their differences were quantified. RESULTS: The mean total tibiotalar ROM was 38.1 degrees (SD 7.8) intraoperatively, and the postoperative total tibiotalar ROM was 24.2 degrees (SD 9.7) (P < .001), indicating that a mean of 65.3% (SD 26.7) of the intraoperative motion was maintained postoperatively. Intraoperative dorsiflexion (mean 11.6 [SD 4.5] degrees) showed no evidence of difference from postoperative dorsiflexion (mean 11.4 [SD 5.8] degrees, P > .99), indicating that a median of 95.6% (interquartile range: 66.2-112) of the intraoperative maximum dorsiflexion was maintained postoperatively. However, there was a significant difference between intraoperative plantarflexion (mean 26.4 [SD 6.3]) and postoperative plantarflexion (12.8 [SD 6.9] degrees, P < .001), indicating a mean 50.6% (SD 29.6) of intraoperative motion maintained in the postoperative assessment. There was an improvement of 2.5 degrees in the total tibiotalar ROM following TAA with statistical significance (P < .043). CONCLUSION: This study revealed a significant difference between intraoperative ankle ROM and ankle ROM approximately 1 year after anterior-approach, fixed-bearing TAA, mainly due to plantarflexion motion restriction. Minimal difference in dorsiflexion suggests the importance of achieving the desired postoperative dorsiflexion motion during the surgery using the best possible adjunct procedures. LEVEL OF EVIDENCE: Level IV, case series.

Effects of Travel Distance on Complications and Outcomes in Total Ankle Arthroplasty.

Owing to the last decade's increase in the number of total ankle arthroplasty (TAA) procedures performed annually, there is a concern that the disproportionate distribution of orthopaedic surgeons who regularly perform TAA may impact complications and/or patient satisfaction. This study examines patient-reported outcomes and complications in TAA patients who had to travel for surgery compared to those treated locally. This is a single-center retrospective review of 160 patients undergoing primary TAA between January 2016 and December 2018, with mean age 65 (range: 59-71) years, mean body mass index (BMI) 28.7 kg/m2, 69 (43.1%) females, and mean 1.5 (SD = 0.51) years follow-up. Patients were grouped by distance traveled (<50 miles [n = 89] versus >50 miles traveled [n = 71]). There were no significant differences in rate or type of postoperative complications between the <50 mile group (16.9%) and the >50 mile group (22.5%) (P = .277). Similarly, there were no significant difference in postoperative PROMIS scores between the groups (P = .858). Given uneven distribution of high-volume surgeons performing TAA, this is important for patients who are deciding where to have their TAA surgery and for surgeons on how to counsel patients regarding risks when traveling longer distances for TAA care.Levels of Evidence: Level III: Retrospective Cohort Study.

AAV2 vector optimization for retinal ganglion cell-targeted delivery of therapeutic genes.

Recombinant adeno-associated virus (AAV)-2 has significant potential as a delivery vehicle of therapeutic genes to retinal ganglion cells (RGCs), which are key interventional targets in optic neuropathies. Here we show that when injected intravitreally, AAV2 engineered with a reporter gene driven by cytomegalovirus (CMV) enhancer and chicken ß-actin (CBA) promoters, displays ubiquitous and high RGC expression, similar to its synthetic derivative AAV8BP2. A novel AAV2 vector combining the promoter of the human RGC-selective γ-synuclein (hSNCG) gene and woodchuck hepatitis post-transcriptional regulatory element (WPRE) inserted upstream and downstream of a reporter gene, respectively, induces widespread transduction and strong transgene expression in RGCs. High transduction efficiency and selectivity to RGCs is further achieved by incorporating in the vector backbone a leading CMV enhancer and an SV40 intron at the 5' and 3' ends, respectively, of the reporter gene. As a delivery vehicle of hSIRT1, a 2.2-kb therapeutic gene with anti-apoptotic, anti-inflammatory and anti-oxidative stress properties, this recombinant vector displayed improved transduction efficiency, a strong, widespread and selective RGC expression of hSIRT1, and increased RGC survival following optic nerve crush. Thus, AAV2 vector carrying hSNCG promoter with additional regulatory sequences may offer strong potential for enhanced effects of candidate gene therapies targeting RGCs.

Early Survivorship, Clinical and Radiographic Outcomes of a Modular Augmented Revision Total Ankle Arthroplasty System.

BACKGROUND: As the number of total ankle arthroplasties (TAAs) performed annually increases, there is increased demand for modular revision implants. There is limited early survivorship and clinical outcome data for the INVISION Total Ankle Arthroplasty System (Wright Medical Technology/Stryker). This study aims to determine early implant survivorship, complications, and radiographic and patient-reported outcomes (PROs) of the INVISION implant in the revision setting. METHODS: This is a single-institution retrospective review of adult patients who underwent revision TAA with the INVISION implant with minimum 2-year follow-up. Demographics, complications, radiographic data, and PROs (PROMIS) were collected. The primary outcome was implant survivorship. Secondary outcomes were reoperation, radiographic complications, and PROs. RESULTS: Nineteen patients underwent revision INVISION TAA with mean follow-up of 3.5 years. INVISION revision TAA was used for tibial (n = 6) or talar (n = 7) component subsidence, recurrent tibiotalar malalignment (valgus = 1, varus = 3), and postinfection bone loss (n = 2). Two-year implant survivorship was 100%. There were no reoperations. One patient had lucency of the talar component at 6 months post TAA revision with INVISION. One patient had talar subsidence at final follow-up. Two-year postoperative follow-up PROMIS domains improved significantly (P < .05). CONCLUSION: There was excellent short-term survivorship of the INVISION TAA implant, with no failures. There were significant improvements in PROs and low rates of subsidence and lucencies. The results of this study support using the INVISION implant in the revision TAA setting. LEVEL OF EVIDENCE: Level III, retrospective cohort.

Phase I Safety and Feasibility Pilot of Hepatic Artery Infusion Chemotherapy in a Rural Catchment Area Using The Codman Vascular Catheter with The Medtronic SynchroMed II Pump for Intrahepatic Cancers.

BACKGROUND: Discontinuation of the Codman 3000 pump in 2018 left no Food and Drug Administration (FDA)-approved hepatic artery infusion (HAI) device for unresectable colorectal liver metastases (uCLM) and intrahepatic cholangiocarcinoma (uIHC). Historically, HAI has been performed at academic medical centers in large metropolitan areas, which are often inaccessible to rural patients. Consequently, feasibility of dissemination of HAI to rural populations is unknown. PATIENTS AND METHODS: Under an FDA investigational device exemption, we opened the only HAI program in Kentucky and enrolled patients with uCLM and uIHC in a phase I clinical trial. The trial examined the safety of the hybrid Codman catheter/Medtronic SynchroMed II pump (hCMP) combination, defined as successful completion of one cycle of HAI chemotherapy. Rural feasibility was assessed by number of missed pump fills appointments. RESULTS: A total of 21 patients (n = 17 uCLM, n = 4 uIHC) underwent hCMP implantation before accrual was stopped early owing to FDA approval of the Intera 3000 pump. 20/21 (95%) patients met the primary safety endpoint. Serious adverse events (AEs) included a grade 5 coronavirus disease 2019 (COVID-19) infection (n = 1) and a grade 3 catheter erosion into the bowel (n = 1). Biliary sclerosis developed in two patients (9.5%). Median distance to infusion center was 47.6 miles (2-138 miles), and 62% were from Appalachia, yet there were no missed pump fill appointments. The 2-year overall survival was 82.4% (uCLM) and 50% (uIHC). CONCLUSIONS: The hCMP device had an acceptable safety profile. Despite the complexity of starting a new HAI program, early results showed feasibility for HAI delivery in a rural catchment area and comparable outcomes to larger urban-based HAI centers.

Midterm Clinical Outcomes, Radiographic Outcomes, and Survivorship of the Infinity Total Ankle Arthroplasty.

BACKGROUND: The Infinity Total Ankle Arthroplasty (Stryker, Mahwah, NJ) is a low-profile fixed-bearing implant first introduced in 2014. Although the short-term survivorship (2-4 years follow-up) and complication rates of the Infinity TAA have been reported, there are limited midterm outcome reports. The aim of this study was to describe the survivorship and clinical outcomes of a single-center experience with the Infinity implant at minimum 5-year follow-up. METHODS: Retrospective review of 65 ankles that underwent primary total ankle arthroplasty (TAA) with the Infinity implant was conducted. Mean clinical follow-up was 6.5 years (range, 5.0-8.0). Preoperative and postoperative radiographs were measured to assess tibiotalar alignment, periprosthetic lucencies, and cysts. Preoperative, 2-year, and 5-year postoperative Foot and Ankle Outcome Score (FAOS) subscores were compared to assess midterm clinical outcomes. Survivorship assessment was determined by removal of 1 or both metallic implant components. RESULTS: Survivorship of the implant was 93.8% at final follow-up. There were 4 revisions: 2 for tibial implant loosening, 1 for talar loosening, and 1 for loosening of both components. Three of the 4 revisions occurred within the first 2 years following implantation, and the last failure occurred at 7 years postoperatively. There were 11 reoperations in 10 (15%) ankles and 3 wound complications. There were 17 ankles (26.2%) with radiographic abnormalities around the implants, including 14 cases with tibial component lucencies and 4 cases of periimplant cysts. FAOS outcome measurement showed general stability between 2 and 5 years and substantial improvement from preoperative status. CONCLUSION: To date this study is the largest midterm report on the Infinity total ankle prosthesis, with 65 implants at a mean follow-up of 6.5 years. We found good midterm implant survivorship, and patients experienced significant improvements in FAOS outcome scores and radiographic alignment at final follow-up. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Pharmacokinetics, safety, and tolerability of inhaled remdesivir in healthy participants.

Intravenous remdesivir (RDV) is US Food and Drug Administration-approved for hospitalized and nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS-443902, and other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure and maximize exposure at the site of action. This study evaluated the pharmacokinetics (PK) and safety of inhaled RDV in healthy adults. This phase Ia, randomized, placebo-controlled study evaluated inhaled RDV in healthy participants randomized 4:1 to receive RDV or placebo as single doses (4 cohorts) or multiple once-daily doses (3 cohorts). Doses in cohorts 1-6 were administered as an aerosolized solution for inhalation through a sealed facemask; doses in cohort 7 were administered as an aerosolized solution for inhalation through a mouthpiece. Safety was assessed throughout the study. Seventy-two participants were enrolled (inhaled RDV, n = 58 and placebo, n = 14). Following single RDV doses, RDV, GS-704277, and GS-441524 plasma PK parameters indicated dose-proportional increases in area under the concentration-time curve (AUC) extrapolated to infinite time, AUC from time zero to last quantifiable concentration, and maximum observed concentration. Analyte plasma concentrations after multiple RDV doses were consistent with those for single-dose RDV. Analyte plasma exposures were lower when RDV was administered with a mouthpiece versus a sealed facemask. The most common adverse events included nausea, dizziness, and cough. Single- and multiple-dose inhaled RDV exhibited linear and dose-proportional plasma PK. Administration of RDV via inhalation was generally safe and well-tolerated.

Outcomes of Total Ankle Arthroplasty in Postfracture Ankle Arthritis.

BACKGROUND: Ankle arthritis that develops after fracture accounts for a significant portion of ankle arthritis necessitating total ankle arthroplasty (TAA). It remains unknown whether TAA in postfracture patients produces equivalent outcomes to those without fracture history. The purpose of this study was to evaluate the medium-term outcomes of TAA in postfracture ankle arthritis compared to those without fracture history. METHODS: This study reviewed 178 ankles from 171 consecutive patients who underwent TAA in our institution between 2007 and 2017 and completed a minimum 5-year follow-up. Four different TAA systems were utilized by 6 surgeons. Based on fracture history, patients were divided into 2 groups: the postfracture group (n = 63; median age 65.7 years; median follow-up 5.9 years) and the nonfracture group (n = 115; median age 64.4 years; median follow-up 6.2 years). Types and rates of complications including revision and reoperation were compared. Minimum 5-year Foot and Ankle Outcome Score (FAOS) and postoperative improvement were investigated. A subgroup analysis was performed to determine whether outcomes differ between intraarticular fracture patients (n = 43) and extraarticular fracture patients (n = 20). RESULTS: Both groups exhibited comparable postoperative improvement and final FAOS scores. The postfracture group had a significantly higher reoperation rate than the nonfracture group (20 of 63, 31.7%, vs 17 of 115, 14.8%; P = .011), with gutter impingement being the most common cause. There were 3 revisions in each group. In the subgroup analysis, we found no evidence of statistical difference between the intraarticular fracture group and the extraarticular fracture group in terms of FAOS scores, revision, and reoperation rates. CONCLUSION: In this single-center, retrospective comparative study, we found total ankle arthroplasty in patients with a history of fractures around the ankle joint had no evidence of statistical difference in patient-reported outcomes and implant survivorship but led to a higher rate of nonrevision reoperation following surgery. In the much smaller subset of patients with previous fracture, we did not find that those with a history of intraarticular fracture had inferior outcomes after TAA when compared to those with a history of extraarticular fracture. LEVEL OF EVIDENCE: Level III, case-control study.

Outpatient Total Ankle Arthroplasty (TAA) as a Rising Alternative to Inpatient TAA: A Database Analysis.

BACKGROUND: There is growing evidence that total ankle arthroplasty (TAA) can safely be performed as an outpatient procedure, with the benefit of decreased health care expenses and improved patient satisfaction. The purpose of our study was to compare readmissions, arthroplasty failures, infections, and annual trends between outpatient and inpatient TAA using a large publicly available for-fee database. METHODS: The PearlDiver Database was queried to identify outpatient and inpatient TAA-associated claims for several payer types from January 2010 to October 2021. Preoperative patient characteristics and annual trends were compared for inpatient and outpatient TAA. International Classification of Diseases, Ninth and Tenth Revision, diagnosis codes were used to identify infections and arthroplasty failures. Complications rates were compared after matching patients by age, gender, and the following comorbidities: diabetes, smoking, congestive heart failure (CHF), hypertension (HTN), obesity, and chronic kidney disease (CKD). RESULTS: A total of 12 274 patients were included in the final exact-matched analysis for complications, with 6137 patients in each group. Outpatients had a significantly lower rate of readmission within 90 days (2.6% vs 4.0%, P < .001), arthroplasty failure (4.1% vs 6.9%, P < .001), and infection (2.4% vs 3.1%, P = .015). Among database enrollees, outpatient TAA has risen in proportion to inpatient TAA from 2019 to 2021. CONCLUSION: Outpatient TAA had lower rates of risk-adjusted readmission, arthroplasty failure, and infection compared to inpatient TAA. LEVEL OF EVIDENCE: Level III, retrospective comparative database study.

Early outcomes of the Exactech Vantage fixed-bearing total ankle replacement.

Aims: The Vantage Total Ankle System is a fourth-generation low-profile fixed-bearing implant that has been available since 2016. We aimed to describe our early experience with this implant. Methods: This is a single-centre retrospective review of patients who underwent primary total ankle arthroplasty (TAA) with a Vantage implant between November 2017 and February 2020, with a minimum of two years' follow-up. Four surgeons contributed patients. The primary outcome was reoperation and revision rate of the Vantage implant at two years. Secondary outcomes included radiological alignment, peri-implant complications, and pre- and postoperative patient-reported outcomes. Results: There were 168 patients (171 ankles) included with a mean follow-up of 2.81 years (2 to 4.6) and mean age of 63.0 years (SD 9.4). Of the ten ankles with implant failure (5.8%), six had loosening of the tibial component. In the remaining four failed implants, one was due to periprosthetic joint infection (PJI), one was due to loosening of the talar component, and two were due to loosening of both the tibial and talar components. Seven patients underwent reoperation: irrigation and debridement for superficial infection (n = 4); bone grafting for cysts (n = 2); and open reduction internal fixation (n = 1). Asymptomatic peri-implant lucency/subsidence occurred in 20.1% of ankles, with the majority involving the tibial component (n = 25). There were statistically significant improvements in PROMs in all domains. Conclusion: Short-term results of this implant demonstrate early survival comparable to the reported survivorship of similar low-profile, non-stemmed implants. Radiological lucency occurred more commonly at the tibial component, and revisions occurred primarily due to loosening of the tibial component. Further research is needed to evaluate longer-term survivorship.