Can ChatGPT-4 Diagnose and Treat Like an Orthopaedic Surgeon? Testing Clinical Decision Making and Diagnostic Ability in Soft-Tissue Pathologies of the Foot and Ankle.

INTRODUCTION: ChatGPT-4, a chatbot with an ability to carry human-like conversation, has attracted attention after demonstrating aptitude to pass professional licensure examinations. The purpose of this study was to explore the diagnostic and decision-making capacities of ChatGPT-4 in clinical management specifically assessing for accuracy in the identification and treatment of soft-tissue foot and ankle pathologies. METHODS: This study presented eight soft-tissue-related foot and ankle cases to ChatGPT-4, with each case assessed by three fellowship-trained foot and ankle orthopaedic surgeons. The evaluation system included five criteria within a Likert scale, scoring from 5 (lowest) to 25 (highest possible). RESULTS: The average sum score of all cases was 22.0. The Morton neuroma case received the highest score (24.7), and the peroneal tendon tear case received the lowest score (16.3). Subgroup analyses of each of the 5 criterion using showed no notable differences in surgeon grading. Criteria 3 (provide alternative treatments) and 4 (provide comprehensive information) were graded markedly lower than criteria 1 (diagnose), 2 (treat), and 5 (provide accurate information) (for both criteria 3 and 4: P = 0.007; P = 0.032; P < 0.0001). Criteria 5 was graded markedly higher than criteria 2, 3, and 4 (P = 0.02; P < 0.0001; P < 0.0001). CONCLUSION: This study demonstrates that ChatGPT-4 effectively diagnosed and provided reliable treatment options for most soft-tissue foot and ankle cases presented, noting consistency among surgeon evaluators. Individual criterion assessment revealed that ChatGPT-4 was most effective in diagnosing and suggesting appropriate treatment, but limitations were seen in the chatbot's ability to provide comprehensive information and alternative treatment options. In addition, the chatbot successfully did not suggest fabricated treatment options, a common concern in prior literature. This resource could be useful for clinicians seeking reliable patient education materials without the fear of inconsistencies, although comprehensive information beyond treatment may be limited.

Platelet-Rich Plasma vs Extracorporeal Shock Wave Therapy in the Treatment of Plantar Fasciitis at 3-6 Months: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Plantar fasciitis (PF) is a common foot disorder with variability in treatment strategy. Two effective management techniques include platelet-rich plasma (PRP) injections and extracorporeal shock wave therapy (ESWT). The purpose of this meta-analysis is to compare the effectiveness of PRP vs ESWT in the management of PF. METHODS: A systematic search was performed of PubMed, Cochrane, and Google Scholar for randomized controlled trials comparing PRP to ESWT. Studies met inclusion criteria if mean and SDs for visual analog scale (VAS) pain scores and plantar fascia thickness (PFT) were reported. Mean differences were used to compare VAS pain score and PFT between PRP and ESWT. RESULTS: Six randomized controlled trials, comparing a total of 214 subjects in the PRP group and 218 subjects in the ESWT group, were analyzed. A significantly greater statistical improvement was seen in the PRP group in VAS pain (mean difference = -0.67 [95% CI -1.16, -0.18], P = .007) and plantar fascia thickness (PFT) (mean difference = -0.56 [95% CI -0.77, -0.35], P < .001). CONCLUSION: PRP had a statistically higher pain reduction than ESWT, but the difference does not reach clinical significance in this meta-analysis.

Biomechanical Effects of Subtalar Joint Fusion and Medial Ligament Reconstruction in Simulated Progressive Collapsing Foot Deformity.

BACKGROUND: The purpose of this study is to investigate the biomechanical effect of medial displacement calcaneal osteotomy (MDCO), subtalar joint fusion (SF), and medial ligament reconstruction (MLR: deltoid-spring ligament) in a severe flatfoot model. We hypothesized that (1) combination of MDCO and SF improves the tibiotalar and foot alignment in severe progressive collapsing foot deformity (PCFD) cadaver model. (2) However, if a residual valgus heel alignment remains after MCDO and SF, it can lead to increased medial ligament strain, foot malalignment, and tibiotalar valgus tilt, which will be mitigated by the addition of MLR. METHODS: Ten fresh-frozen cadaveric foot specimens were used to create a severe flatfoot model. The foot alignment changes, including the talo-first metatarsal angle in the axial and sagittal planes, subtalar angle, and tibiotalar angle in the coronal plane, were measured. The angles were measured at the initial condition, after creating the severe flatfoot model, and after each successive reconstructive procedure in the following order: (1) MDCO, (2) SF, and (3) MLR. RESULTS: Tibiotalar valgus tilt was decreased with the MDCO procedure: 4.4 vs 1.0 degrees (P = .04). Adding in situ SF to the MDCO led to increased tibiotalar tilt to 2.5 degrees was different from the initial condition (P = .01). Although the tibiotalar valgus tilt was significantly decreased after adding the MLR to the MDCO/SF procedure compared with the severe flatfoot model (0.8 vs 4.4 degrees, P = .03), no significant difference in the tibiotalar valgus tilt was observed between MDCO/SF and MDCO/SF with MLR. CONCLUSION: Our results demonstrated that MDCO significantly improved forefoot abduction and medial arch alignment, with no significant additional improvement observed with addition of SF. Following SF, a residual valgus heel alignment can contribute to subsequent tibiotalar valgus tilt. The addition of MLR did not show significantly decreased tibiotalar valgus tilt following SF. CLINICAL RELEVANCE: Residual valgus heel alignment after subtalar joint fusion in the surgical treatment of PCFD can lead to increased medial ligament strain. Although MLR might be considered for providing medial stability, it may not necessarily prevent the development of tibiotalar valgus tilt.

Utilization of PROMIS Neuropathic Pain Quality for Detection and Monitoring Neuropathic Pain in Heel Pain Patients.

Background: Diagnosis and management of neuropathic pain (NP) in foot and ankle patients remain challenging. We investigated the plausibility of using Patient-Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Quality (PQ-Neuro) as an initial screening tool to detect NP and track the treatment effects. Methods: Patients with heel pain were prospectively recruited and grouped to no-NP, mild-NP, and severe-NP based on the initial PROMIS PQ-Neuro t scores. Pain Interference (PI), Physical Function (PF), and Self-Efficacy (SE) scores were evaluated at baseline, 30-day, and 90-day follow-up. Other factors such as age, smoking, body mass index (BMI), low back/neck pain, anxiety/depression, and medications were analyzed. Linear mixed modeling was used to assess the main effects of time and NP on PROMIS t scores, comparing minimal clinically important difference (MCID). Results: Forty-eight patients with mean age of 52.4 years were recruited. Using the PROMIS PQ-Neuro as the assessment tool, 33 patients (69%) were detected to have NP at baseline-23 (48%) mild and 10 (21%) severe. BMI was the only independent factor associated with NP (P = .011). Higher baseline PQ-Neuro t score was significantly associated with higher follow-up PQ-Neuro (P < .001), PI (P = .005), and lower SE (P = .04) across time points. Patients with NP showed lower PF at baseline with significantly less improvement in PF (3 vs 9.9, P = .035) and did not meet MCID. Conclusion: Baseline PROMIS PQ-Neuro ≥46 was significantly associated with worse PI and SE across all time points, with less clinically significant improvements in PF. Prevalence of NP in heel pain patients was high. The PROMIS PQ-Neuro may serve as a valuable tool for detection of NP and guiding clinical treatment decision pathways for heel pain patients. Level of Evidence: Level III, prospective cohort study.

The Burden of Revision Total Ankle Replacement Has Increased From 2010 to 2020.

Background: Total ankle replacement (TAR) surgery has increased in recent decades. The aim of this study was to investigate the evolving burden of revision surgery and risk factors and timing of revision or explant. Methods: Using the 2010 to 2020 PearlDiver M151Ortho data set, this retrospective cohort study identified primary TAR, TAR revision, and TAR explant patients via Current Procedural Terminology (CPT) and International Classification of Disease Procedural (ICD-P) codes. This database contains billing claims information across all payers and sites of care in the United States. Patient factors investigated included age, sex, and Elixhauser Comorbidity Index (ECI). Annual incidence for primary TAR was normalized per 100 000 covered lives in the data set for each year of study and recorded. Annual incidence of revision TAR and explant were normalized per 100 TARs performed for each year of study. Multivariate logistic regression analyses were performed to determine independent risk factors for revision TAR or explant. For explants, the eventual intervention by 2 years was analyzed. Ten-year timing and survival to revision or explant surgery following unilateral TAR were characterized. Results: A total of 10 531 primary, 1218 revision, and 1735 explant TARs were identified. After normalization, TAR utilization increased by 284% from 2010 to 2020, annual TAR revisions rose 28%, and annual TAR explants decreased 65%. Independent predictors of revision TAR were younger age (odds ratio [OR] 1.29 per decade decrease) and higher ECI (OR 1.23 per 2-point increase). Independent predictors of explant included younger age (OR 1.80 per decade decrease), female sex (OR 1.17), and higher ECI (OR 1.35 per 2-point increase). The 10-year implant survival rate was 91.8%, of which 73% of revisions and 83% of explants occurred in the first 3 years following index TAR. Conclusion: TAR utilization has grown substantially over the past decade, with minimal increases in the annual rate of revision surgery with respect to index procedures performed. Level of Evidence: Level III, retrospective cohort study.

Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection.

Introduction: Infection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. Staphylococcus aureus is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies against S. aureus for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and may suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of S. aureus- infected DFU. Methods: This study compared the transcriptome profile of 21 patients with S. aureus- infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotic therapy. Blood samples were collected at the recruitment (0 weeks) and 8 weeks after therapy to isolate peripheral blood mononuclear cells (PBMCs). We analyzed the PBMC expression of transcriptomes at two different time points (0 versus 8 weeks). Subjects were further divided into two groups at 8 weeks: healed (n = 17, 80.95%) versus non-healed (n = 4, 19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed. Results and discussion: An increased expression of IGHG1, IGHG2, IGHG3, IGLV3-21, and IGLV6-57 was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (HIST1H2AJ, HIST1H2AL, HIST1H2BM, HIST1H3B, and HIST1H3G) were upregulated at the initial phase of active infection at 0 weeks. CD177 and RRM2 were also upregulated at the initial phase of active infection (0 weeks) compared with that at 8 weeks of follow-up. Genes of heat shock protein members (HSPA1A, HSPE1, and HSP90B1) were high in not healed patients compared with that in healed patients 8 weeks after therapy. The outcome of our study suggests that the identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection and assessing severity and host immune response to therapies.

Clinical presentation of group B Streptococcus-infected diabetic foot ulcers.

OBJECTIVE: Group B Streptococcus (GBS) is a common pathogen in diabetic foot ulcers (DFUs), where it has been found to result in higher rates of soft tissue infection and amputation despite appropriate treatment. In this study, we aim to investigate clinical characteristics and prognosis of GBS DFU infections, especially those with tenosynovial involvement. We hypothesise that GBS-infected DFUs with tenosynovial involvement leads to an increased number of recurrent infections and unexpected returns to the operating room. METHOD: Data were retrospectively collected from GBS-infected DFU patients surgically treated by an orthopaedic foot and ankle surgeon over a four-year period. Demographics, comorbidities, initial laboratory values and culture results from infected bone samples were recorded. Clinical outcome was assessed by recurrent infection and unplanned reoperation(s) within 3 months following the initial surgery. RESULTS: In total, 72 patients were treated for GBS-infected DFUs. Intra-operative culture of infected bone identified GBS in 16 patients (22.2%). Significantly more black patients (p=0.017) were afflicted by GBS DFUs. Patients with GBS DFUs had higher initial haemoglobin A1C levels (p=0.019), and those with tenosynovial involvement were likely to require reoperation (p=0.036) and had a greater total number of surgeries (p=0.015) than those without. CONCLUSION: GBS-infected DFUs are more common in black patients and those with elevated haemoglobin A1Cs. GBS infections with tenosynovial involvement are particularly destructive and require aggressive treatment by surgeons.

Clinical Improvement Following Operative Management of Ankle Fractures Among Patients With and Without Moderate to High Depressive Symptoms: An Analysis Using PROMIS.

Background: Understanding the recovery trajectory following operative management of ankle fractures can help surgeons guide patient expectations. Further, it is beneficial to consider the impact of mental health on the recovery trajectory. Our study aimed to address the paucity of literature focused on understanding the recovery trajectory following surgery for ankle fractures, including in patients with depressive symptoms. Methods: From February 2015 to March 2020, patients with isolated ankle fractures were asked to complete Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression questionnaires as part of routine care at presentation and follow-up time points. Linear mixed effects regression models were used to evaluate the patient recovery pattern, comparing the preoperative time point to <3 months, 3-6 months, and >6 months across all patients. Additional models that included the presence of depression symptoms as a covariate were then used. Results: A total of 153 patients met inclusion criteria. By 3-6 months, PROMIS PF (ß: 9.95, 95% CI: 7.97-11.94, P < .001), PI (ß: -10.30, 95% CI: -11.87 to -8.72, P < .001), and Depression (ß: -5.60, 95% CI: -7.01 to -4.20, P < .001) improved relative to the preoperative time point. This level of recovery was sustained thereafter. When incorporating depressive symptoms into our model as a covariate, the moderate to high depressive symptoms were associated with significantly and clinically important worse PROMIS PF (ß: -4.00, 95% CI: -7.00 to -1.00, P = .01) and PI (ß: 3.16, 95% CI: -0.55 to 5.76, P = .02) scores. Conclusion: Following ankle fracture surgery, all patients tend to clinically improve by 3-6 months postoperatively and then continue to appreciate this clinical improvement. Although patients with moderate to high depressive symptoms also clinically improve following the same trajectory, they tend to do so to a lesser level than those who have low depressive symptoms. Level of Evidence: Level III, case-control study.

Home and Outpatient Physical Therapy Utilization Following Total Ankle Replacement.

Background: Physical therapy (PT) following total ankle replacement (TAR) is often considered, but guidelines for its use are not standardized. Although patient factors may dictate recommendations, this retrospective cohort study aims to characterize baseline utilization practices to set the stage for establishing generalizable recommendations. Methods: TAR patients were identified from the 2010-2019 M91 Ortho PearlDiver data set based on administrative coding. Patient factors were extracted, including age, sex, Elixhauser Comorbidity Index (ECI), region of the country in which patients' surgery was performed (Midwest, Northeast, South, West), and insurance plan (commercial, Medicaid, Medicare). The incidence, timing, and frequency of home or outpatient PT utilization in the 90 days following TAR were identified. Inpatient PT was not captured. Univariate and multivariate logistic regression analyses allowed identification of predictive factors for PT utilization. Results: Of 5412 TAR patients identified, postoperative PT services were used by 2453 (45.3%). Most PT was outpatient (38.3% of the study population) compared to home (4.1% of the study population). Weekly utilization of PT was greatest in the first week following surgery (17.7% of PT visits) and thereafter followed a roughly bell-shaped curve, with utilization greatest at 7 weeks following surgery (14.9% of PT visits).Independent predictors of PT utilization following TAR included having surgery performed in the Midwest (relative to the South, OR 1.37, P < .0001), Northeast (OR 1.20, P = .0217), or West (OR 1.26, P < .0021) and having commercial (relative to Medicare, OR 1.87, P < .0001) or Medicaid insurance (OR 1.46, P = .0239). Conclusion: Of 5412 TAR patients, 42.5% used PT within 90 days of surgery. PT utilization was highest in the first and seventh weeks following surgery, and demographic predictors of PT use were defined. Through identification of timing and predictors of PT utilization following TAR, PT care pathways may be better defined. Level of Evidence: Level III, retrospective cohort study.

Emergency Department Visits Within 90 Days of Total Ankle Replacement.

Background: Total ankle replacement (TAR) utilization in the United States has steeply increased in recent decades. Emergency department (ED) visits following TAR impacts patient satisfaction and health care costs and warrant exploration. Methods: This retrospective cohort study utilized the 2010 to 2019 M91Ortho PearlDiver data set to identify TAR patients with at least 90 days of follow-up. PearlDiver contains billing claims data across all sites of care throughout the United States for all indications for care. Patient factors extracted included age, sex, Elixhauser Comorbidity Index (ECI), region of the country in which surgery was performed, insurance plan, and postoperative hospital length of stay. Ninety-day postoperative ED visit incidence, timing, frequency, and primary diagnoses were identified and compared to 1-year postoperative ED visit baseline data. Univariate and multivariate logistic regression analyses were used to determine risk factors for ED visits. Results: Of 5930 TAR patients identified, ED visits within 90 days were noted for 497 (8.4%) patients. Of all ED visits, 32.0% occurred within 2 weeks following surgery. Multivariate analysis revealed several predictors of ED utilization: younger age (odds ratio [OR] 1.35 per decade decrease), female sex (OR 1.20), higher ECI (OR 1.32 per 2-point increase), TAR performed in the western US (OR 1.34), and Medicaid coverage (OR 2.70; 1.71-4.22 relative to Medicare) (P < .05 each). Surgical site issues comprised 78.0% of ED visits, with surgical site pain (57.0%) as the most common problem. Conclusion: Of 5930 TAR patients, 8.4% returned to the ED within 90 days of surgery, with predisposing demographic factors identified. The highest incidence of ED visits was in the first 2 postoperative weeks, and surgical site pain was the most common reason. Pain management pathways following TAR should be able to be adjusted to minimize the occurrence of postoperative ED visits, thereby improving patient experiences and decreasing health care utilization/costs. Level of Evidence: Level III, retrospective cohort study.

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis.

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection-associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin-resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re-emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis.

Treating 'Septic' With Enhanced Antibiotics and 'Arthritis' by Mitigation of Excessive Inflammation.

Bacterial infection within the synovial joint, commonly known as septic arthritis, remains a clinical challenge as it presents two concurrent therapeutic goals of reducing bacterial burden and preservation of articular cartilage from destructive host inflammation. We hypothesized that mitigation of MRSA-induced inflammatory signaling could diminish destruction of articular cartilage in the setting of septic arthritis when used in conjunction with antibiotics. Herein, we provide evidence which supports a new therapeutic notion that concurrent antimicrobial therapy to address the 'septic' component of the disease with inflammation mitigation to manage the destructive 'arthritis' component. We established a murine model to mimic septic knee arthritis, as well as a variety of other inflammatory joint conditions. This murine septic arthritis model, in conjunction with in vitro and ex-vivo models, was utilized to characterize the inflammatory profile seen in active septic arthritis, as well as post-antibiotic treatment, via transcriptomic and histologic studies. Finally, we provided the clinical rationale for a novel therapeutic strategy combining enhanced antibiotic treatment with rifampin and adjuvant immunomodulation to inhibit post-infectious, excess chondrolysis and osteolysis. We identified that septic arthritis secondary to MRSA infection in our murine model led to increased articular cartilage damage compared to various types of inflammatory arthritis. The activation of the pERK1/2 signaling pathway, which is implicated with the mounting of an immune response and generation of inflammation, was increased in intracellular MRSA-infected synovial tissue and persisted despite antibiotic treatment. Trametinib, an inhibitor of ERK signaling through suppression of MEK1/2, alleviated the inflammation produced by the addition of intra-articular, heat-killed MRSA. Further, when combined with vancomycin and rifampin, mitigation of inflammation by pERK1/2 targeting improved outcomes for MRSA septic arthritis by conferring chondroprotection to articular cartilage and diminishing inflammatory osteolysis within bone. Our results support a new therapeutic notion that cell/biofilm-penetrating antibiotics alongside adjuvant mitigation of excessive intra-articular inflammation accomplish distinct therapeutic goals: reduction of bacterial burden and preservation of articular cartilage integrity.

Physical Function and Pain Interference Levels of Hallux Rigidus Patients Before and After Synthetic Cartilage Implant vs Arthrodesis Surgery.

BACKGROUND: Hallux rigidus is a common and painful degenerative condition of the great toe limiting a patient's physical function and quality of life. The purpose of this study was to investigate pre- and postoperative physical function (PF) and pain interference (PI) levels of patients undergoing synthetic cartilage implant hemiarthroplasty (SCI) vs arthrodesis (AD) for treatment of hallux rigidus using the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: PROMIS PF and PI t scores were analyzed for patients who underwent either SCI or AD. Postoperative final PROMIS t scores were obtained via phone survey. Linear mixed model analysis was used to assess differences in PF and PI at each follow-up point. Final follow-up scores were analyzed using independent sample t tests. RESULTS: Total 181 (59 SCI, 122 AD) operatively managed patients were included for analysis of PROMIS scores. Final phone survey was performed at a minimum of 14 (mean 33, range, 14-59) months postoperatively, with 101 patients (40 SCI, 61 AD) successfully contacted. The mean final follow-up was significantly different for SCI and AD: 27 vs 38 months, respectively (P < .01). The mean age of the SCI cohort was lower than the AD cohort (57.5 vs 61.5 years old, P = .01). Average PF t scores were higher in the SCI cohort at baseline (47.1 and 43.9, respectively, P = .01) and at final follow-up (51.4 vs 45.9, respectively, P < .01). A main effect of superior improvement in PF was noted in the SCI group (+4.3) vs the AD group (+2) across time intervals (P < .01). PI t scores were similar between the 2 procedures across time points. CONCLUSION: The SCI cohort reported slightly superior PF t scores preoperatively and at most follow-up time points compared with the arthrodesis group. No differences were found for PI or complication rates between the 2 treatment groups during this study time frame. LEVEL OF EVIDENCE: Level IV, case series.

Comparative study of culture, next-generation sequencing, and immunoassay for identification of pathogen in diabetic foot ulcer.

Treatment of deep musculoskeletal infection (MSKI) begins with accurate identification of the offending pathogen, surgical excision/debridement, and a course of culture-directed antibiotics. Despite this, the incidence of recurrent infection continues to rise. A major contributor to this is inaccurate or negative initial cultures. Accurate identification of the main pathogen is paramount to treatment success. This is especially important in treating diabetic foot infections (DFIs) with limb salvage efforts. This study seeks to utilize standard culture, next-generation sequencing (NGS), and immunoassay for newly synthesized antibodies (NSA) to Staphylococcus aureus and Streptococcus agalactiae for diagnosis. This is a level II prospective observational study approved by our IRB. Thirty patients > 18 years of age who presented with a DFI and underwent surgical debridement or amputation by a single academic orthopedic surgeon from October 2018 to September 2019 were enrolled. Intraoperative samples were obtained from the base of the wound and sent for culture, NGS, and a peripheral blood sample was obtained at the time of diagnosis. NGS and culture were highly correlated for S. aureus (κ = 0.86) and S. agalactiae (κ = 1.0), NSA immunoassay and culture demonstrated a fair correlation for S. aureus (κ = 0.18) and S. agalactiae (κ = 0.67), and NGS and NSA immunoassay demonstrated fair correlation for S. aureus (κ = 0.1667) and S. agalactiae (κ = 0.67). Our study demonstrates a high concordance between culture and NGS in identifying the dominant pathogen in DFU. NGS may be a useful adjunct in DFI diagnosis.

Arthroscopically Assisted Internal Fixation of Foot and Ankle Fractures: A Systematic Review.

BACKGROUND: Patients undergoing fixation for foot and ankle fractures may experience poor outcomes despite achieving apparent anatomic reduction. Adjunct arthroscopy to identify missed concomitant injuries and subtle displacements has been proposed as a vehicle to enhance functional results for these patients. The purpose of this review is to provide an overview of the literature regarding arthroscopically assisted open reduction and internal fixation (AAORIF) methods for commonly encountered foot and ankle injuries including pilon, ankle, and calcaneus fractures published to date. METHODS: A systematic review of the literature was performed using the PubMed database to access all studies reporting on arthroscopically assisted internal fixation methods for pilon, ankle, and calcaneus fractures. Relevant publications were analyzed for details on their respective study designs, the operative technique used, clinical outcomes, outcome instruments used, and reported complications. RESULTS: A total of 32 studies were included in this review. Two studies on pilon fractures, a randomized controlled trial (RCT) and case series with a total of 243 patients, met inclusion criteria. Postoperative articular reductions, bone union, and Mazur scores were found to be significantly better for those using adjunct arthroscopy when compared to those with no arthroscopy use. Patient-reported outcomes were overall reported as excellent for most patients, with no difference in patient-reported outcomes reported in the RCT. For ankle fractures, a total of 17 studies comprising of 2 systematic reviews, 1 meta-analysis, 2 RCTs, 5 retrospective comparative studies, 6 case series, and 1 case-control study met inclusion criteria for this review. Results were mixed, though the overall consensus was that arthroscopy use may help to better visualize concomitant intra-articular injuries and is generally considered safe with at least comparable outcomes to conventional methods. For the calcaneus, 13 studies met the criteria. Two studies were review papers, 8 were case series, and 3 were retrospective comparative studies. A total of 308 patients with 316 fractures formed the basis of analysis. In general, the studies found comparable functional outcomes between with or without arthroscopy use, but found that anatomical reductions were significantly improved with the use of arthroscopy. CONCLUSIONS: Arthroscopy shows promise as a valuable adjunct tool for internal fixation of foot and ankle fractures, though definitive conclusions as to its clinical significance have yet to be drawn because of limited evidence. Potential advantages related to the direct visualization of the fracture site and minimally invasive nature of arthroscopy were suggested throughout studies examined in this review. The presence of intra-articular pathology may lead to unexpectedly poor outcomes seen in some patients who undergo surgical fixation of ankle fractures with an otherwise anatomic reduction on postoperative radiographs; the ability to diagnose and address these lesions with arthroscopy, therefore, has the potential to improve patient outcomes. To date, however, available literature has not shown that significant improvements in anatomical reductions and treatment of these intra-articular injuries provide any improvement in outcomes over standard fixation methods. Few prospective randomized controlled studies have been performed comparing these 2 operative techniques, rendering any suggestion that AAORIF improves clinical outcomes over traditional open fixation difficult to justify. Further research is indicated for what may be a potentially promising surgical adjunct prior to advocating for its routine use in patients.

Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers.

BACKGROUND: Accurate identification of primary pathogens in foot infections remains challenging due to the diverse microbiome. Conventional culture may show false-positive or false-negative growth, leading to ineffective postoperative antibiotic treatment. Next-generation sequencing (NGS) has been explored as an alternative to standard culture in orthopedic infections. NGS is highly sensitive and can detect an entire bacterial genome along with genes conferring antibiotic resistance in a given sample. We investigated the potential use of NGS for accurate identification and quantification of microbes in infected diabetic foot ulcer (DFU). We hypothesize that NGS will aid identification of dominant pathogen and provide a more complete profile of microorganisms in infected DFUs compared to the standard culture method. METHODS: Data were prospectively collected from 30 infected DFU patients who underwent operative treatment by a fellowship-trained orthopedic foot and ankle surgeon from October 2018 to September 2019. The average age of the patient was 60.4 years. Operative procedures performed were irrigation and debridement (12), toe or ray amputation (13), calcanectomies (4), and below-the-knee amputation (1). Infected bone specimens were obtained intraoperatively and processed for standard culture and NGS. Concordance between the standard culture and NGS was assessed. RESULTS: In 29 of 30 patients, pathogens were identified by both NGS and culture, with a concordance rate of 70%. In standard culture, Staphylococcus aureus (58.6%) was the most common pathogen, followed by coagulase-negative Staphylococcus (24.1%), Corynebacterium striatum (17.2%), and Enterococcus faecalis (17.2%). In NGS, Finegoldia magna (44.8%) was the most common microorganism followed by S. aureus (41.4%), and Anaerococcus vaginalis (24.1%). On average, NGS revealed 5.1 (range, 1-11) pathogens in a given sample, whereas culture revealed 2.6 (range, 1-6) pathogens. CONCLUSION: NGS is an emerging molecular diagnostic method of microbial identification in orthopedic infection. It frequently provides different profiles of microorganisms along with antibiotic-resistant gene information compared to conventional culture in polymicrobial foot infection. Clinical use of NGS for management of foot and ankle infections warrants further investigation. LEVEL OF EVIDENCE: Level II, diagnostic study.

Adjuvant antibiotic-loaded bone cement: Concerns with current use and research to make it work.

Antibiotic-loaded bone cement (ALBC) is broadly used to treat orthopaedic infections based on the rationale that high-dose local delivery is essential to eradicate biofilm-associated bacteria. However, ALBC formulations are empirically based on drug susceptibility from routine laboratory testing, which is known to have limited clinical relevance for biofilms. There are also dosing concerns with nonstandardized, surgeon-directed, hand-mixed formulations, which have unknown release kinetics. On the basis of our knowledge of in vivo biofilms, pathogen virulence, safety issues with nonstandardized ALBC formulations, and questions about the cost-effectiveness of ALBC, there is a need to evaluate the evidence for this clinical practice. To this end, thought leaders in the field of musculoskeletal infection (MSKI) met on 1 August 2019 to review and debate published and anecdotal information, which highlighted four major concerns about current ALBC use: (a) substantial lack of level 1 evidence to demonstrate efficacy; (b) ALBC formulations become subtherapeutic following early release, which risks induction of antibiotic resistance, and exacerbated infection from microbial colonization of the carrier; (c) the absence of standardized formulation protocols, and Food and Drug Administration-approved high-dose ALBC products to use following resection in MSKI treatment; and (d) absence of a validated assay to determine the minimum biofilm eradication concentration to predict ALBC efficacy against patient specific micro-organisms. Here, we describe these concerns in detail, and propose areas in need of research.

Prediction of post-interventional physical function in diabetic foot ulcer patients using patient reported outcome measurement information system (PROMIS).

BACKGROUND: Infected diabetic foot ulcer (DFU) patients present with an impaired baseline physical function (PF) that can be further compromised by surgical intervention to treat the infection. The impact of surgical interventions on Patient Reported Outcomes Measurement Information System (PROMIS) PF within the DFU population has not been investigated. We hypothesize that preoperative PROMIS scores (PF, Pain Interference (PI), Depression) in combination with relevant clinical factors can be utilized to predict postoperative PF in DFU patients. METHODS: DFU patients from a single academic physician's practice between February 2015 and November 2018 were identified (n = 240). Ninety-two patients met inclusion criteria with complete follow-up and PROMIS computer adaptive testing records. Demographic and clinical factors, procedure performed, and wound healing status were collected. Spearman's rank correlation coefficient, Chi-Squared tests and multidimensional modelling were applied to all variables' pre- and postoperative values to assess patients' postoperative PF. RESULTS: The mean age was 60.5 (33-96) years and mean follow-up was 4.7 (3-12) months. Over 70 % of the patients' initial PF were 2-3 standard deviations below the US population (n = 49; 28). Preoperative PF (p < 0.01), PI (p < 0.01), Depression (p < 0.01), CRF (p < 0.02) and amputation level (p < 0.04) showed significant univariate correlation with postoperative PF. Multivariate model (r = 0.55) showed that the initial PF (p = 0.004), amputation level (p = 0.008), and wound healing status (p = 0.001) predicted postoperative PF. CONCLUSIONS: Majority of DFU patients present with poor baseline PF. Preoperative PROMIS scores (PF, PI, Depression) are predictive of postoperative PROMIS PF in DFU patients. Postoperative patient's physical function can be assessed by PFpostoperative = 29.42 + 0.34 (PFinitial) - 5.87 (Not Healed) - 2.63 (Amputation Category). This algorithm can serve as a valuable tool for predicting post-operative physical function and setting expectations.

Distinct vasculotropic versus osteotropic features of S. agalactiae versus S. aureus implant-associated bone infection in mice.

Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus (S. aureus) and Group B Streptococcus (GBS, S. agalactiae). Clinically, S. aureus osteomyelitis is associated with local inflammation, abscesses, aggressive osteolysis, and septic implant loosening. In contrast, S. agalactiae orthopaedic infections generally involve soft tissue, with acute life-threatening vascular spread. While preclinical models that recapitulate the clinical features of S. aureus bone infection have proven useful for research, no animal models of S. agalactiae osteomyelitis exist. Here, we compared the pathology caused by these bacteria in an established murine model of implant-associated osteomyelitis. In vitro scanning electron microscopy and CFU quantification confirmed similar implant inocula for both pathogens (~105 CFU/pin). Assessment of mice at 14 days post-infection demonstrated increased S. aureus virulence, as S. agalactiae infected mice had significantly greater body weight, and fewer CFU on the implant and in bone and adjacent soft tissue (p < 0.05). X-ray, µCT, and histologic analyses showed that S. agalactiae induced significantly less osteolysis and implant loosening, and fewer large TRAP+ osteoclasts than S. aureus without inducing intraosseous abscess formation. Most notably, transmission electron microscopy revealed that although both bacteria are capable of digesting cortical bone, S. agalactiae have a predilection for colonizing blood vessels embedded within cortical bone while S. aureus primarily colonizes the osteocyte lacuno-canalicular network. This study establishes the first quantitative animal model of S. agalactiae osteomyelitis, and demonstrates a vasculotropic mode of S. agalactiae infection, in contrast to the osteotropic behavior of S. aureus osteomyelitis.

Clinical utilization of species-specific immunoassays for identification of Staphylococcus aureus and Streptococcus agalactiae in orthopedic infections.

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture-based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigen-specific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti-S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture-related infection (FRI). Anti-S. aureus and anti-GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species-specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture.