Citations

Background : Diabetic-foot osteomyelitis (DFO) is a severe complication of diabetic-foot ulcers associated with delayed healing, amputation, and increased mortality. Machine learning (ML) has increasingly been explored for diagnosis and clinical decision-making in diabetic-foot care; however, the current evidence specific to DFO has not been systematically synthesized. Methods : We performed systematic searches of MEDLINE, Embase, Scopus, and Web of Science for studies published between January 2000 and May 2026. Studies that developed or evaluated ML models for DFO diagnosis, prediction, or outcomes were included. Data extraction was performed using the CHARMS framework, reporting followed PRISMA 2020 and TRIPOD-SRMA recommendations, and methodological quality was evaluated using PROBAST + AI. Due to considerable heterogeneity, narrative synthesis was performed. Results : A total of 10 studies published from 2022 to 2026 met the inclusion criteria. Five studies developed or evaluated ML models with a direct DFO diagnostic endpoint, one additional study evaluated model explainability, and four evaluated complementary DFO-relevant diabetic-foot applications. Reported discrimination ranged from 0.879 to 0.998, but comparisons were limited by differences in clinical endpoints, reference standards, input modalities and validation strategies. Only one direct DFO model was externally validated, and no study developed a multimodal model combining clinical and imaging data. Conclusion : Current evidence is limited by heterogeneous methodologies, limited external validation, and inconsistent reporting despite promising discrimination reported by several models. Future studies should evaluate whether multimodal models integrating clinical and imaging data provide incremental value over unimodal approaches, with external validation, calibration, and clinical utility assessment before clinical implementation.

Abstract Fungal periprosthetic joint infection (PJI) is a rare but serious complication of joint arthroplasty, with variable management and poorly defined outcomes. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching Ovid MEDLINE, Embase, Scopus, and Ovid Cochrane Central. Cohort studies were included in the quantitative synthesis, while case reports and series were reviewed qualitatively. Outcomes were treatment success, failure, reinfection, and mortality. We included 160 studies: 42 cohort studies and 118 case reports or case series, with 1,025 fungal PJI cases. Pooled rates were 66.5% for treatment success, 36.5% for failure, 16.6% for reinfection, and 9.6% for mortality. Success and failure were extracted independently using study-specific definitions and are not necessarily complementary. Treatment-strategy estimates were descriptive; studies reporting DAIR had lower pooled success, but findings should be interpreted cautiously because of differences in patient selection, study design, and outcome definitions. These findings cannot establish comparative effectiveness.

Abstract: Kimura disease typically presents with painless head and neck swelling in young adults of Asian descent, accompanied by peripheral eosinophilia and elevated serum IgE. We report a case of Kimura disease in a woman in her early 30s presenting with a slowly enlarging epitrochlear mass, diffuse encasement of the median and medial brachial cutaneous nerves, and a concurrent prurigo nodularis-like papular rash affecting all 4 extremities. The diagnosis required over 1 year of investigation and 5 tissue specimens, including 2 nondiagnostic core-needle biopsies, before near total excision was performed. The excision revealed characteristic histopathologic features, including hyperplastic reactive secondary lymphoid follicles with preserved architecture, a marked eosinophilic infiltrate with eosinophilic microabscesses, postcapillary venule proliferation, and patternless stromal fibrosis. Immunohistochemistry demonstrated a raised IgG4:IgG plasma cell ratio of approximately 1:1, with 150–200 IgG4-positive plasma cells per high-power field, raising the differential of IgG4-related disease; however, the absence of storiform fibrosis and obliterative phlebitis, combined with the clinical and serologic profile, favored Kimura disease. This case is notable for its rare epitrochlear location, extensive neural involvement, concurrent diffuse cutaneous eruption, and histopathologic overlap with IgG4-related disease, highlighting the diagnostic challenges posed by atypical presentations of Kimura disease.

Abstract Background Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Methods Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. Results The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events–related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. Conclusions A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.

Abstract Background Prosthetic joint infection (PJI) represents an important complication of total joint arthroplasty, affecting approximately 2% of patients. However, considerable heterogeneity in outcome definitions renders cross-study and clinical comparisons challenging. Methods We performed a meta-epidemiological study and systematic review of cohort studies and randomized controlled trial (RCTs) reporting clear definitions of PJI outcomes. Relevant data regarding outcome definitions of treatment success or failure were extracted and categorized into 7 outcome domains: clinical signs and symptoms, imaging, microbiology, mortality, antibiotics-related, surgical-related, and histology. A network plot was generated to visualize domains combinations. Data on patient-reported outcome measures (PROMs) were also collected. Based on these results, we finally proposed a working definition of PJI core outcome set. Results The literature search identified 7585 references, leading to 461 studies. The majority were retrospective (416/461, 90.2%), with limited representation of prospective studies (37/461, 8.0%) and RCTs (8/461, 1.7%). Outcome reporting was highly heterogeneous, with the clinical criterion being the most frequently used domain, combined with microbiological, surgical, and mortality-related outcomes. In contrast, histopathological, imaging, and antibiotic-related criteria were rarely reported. Thirty-six PROMs were included in only 111 (24.1%) studies, most commonly the Knee Society Score (26%) and Harris Hip Score (23%). Conclusions We showed substantial heterogeneity in PJI outcome definitions, with inconsistent reporting across key domains, limiting comparability and evidence synthesis. Standardized, consensus-based outcomes incorporating patient-reported and antibiotic-related measures are needed, and the proposed core outcome set may support harmonized research and clinical practice aligned with the new PJI definition.

Abstract Background Postoperative spinal implant infections (PSIIs) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. Methods We conducted a multicenter retrospective cohort study across 10 US academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤ 12 weeks versus >12 weeks. Results A total of 116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free 6 weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71; 95% CI .48–1.07; P = .10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations > 12 weeks did not significantly reduce the risk of failure (aHR 1.01; 95% CI .62–1.64; P = .99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85; 95% CI .62–1.16; P = .30). Conclusions Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

Abstract Background The number of arthroplasty procedures and infection-related complications, including prosthetic joint infections (PJIs) and surgical site infections (SSIs), continues to rise. Although current guidelines recommend cefazolin or cefuroxime as the first-line perioperative prophylactic antibiotic, substitutions with non-cephalosporins remain common, especially among patients with reported β-lactam allergies. These substitutions may increase infection risk and healthcare costs. Evidence comparing outcomes across antibiotic classes remains variable. Methods We conducted a systematic review and meta-analysis of studies comparing single-agent cephalosporin versus single-agent non-cephalosporin prophylaxis in adults undergoing primary arthroplasty. Cochrane, Embase, Medline, Scopus, and Web of Science were searched from database inception through January 2025. Random-effect or fixed-effect models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses stratified results by cephalosporin type, study era, and risk of bias. Results Twenty-three studies (7 randomized controlled trials and 16 observational studies) were included, encompassing 191 527 arthroplasties in the cephalosporin arm and 20 058 in the non-cephalosporin arm. The odds of PJI were lower with cephalosporins (OR 0.59; 95% CI, .46–.75). No overall difference was observed for SSI (OR 0.70; 95% CI, .36–1.36), though post-2013 studies and the cefazolin subgroup demonstrated a significant protective effect. Randomized trial estimates were limited and heterogeneous and did not reach statistical significance. Certainty of evidence was graded as moderate. Conclusions Cephalosporins, particularly cefazolin or cefuroxime, remain the preferred prophylactic agents for primary arthroplasty. This quantitative synthesis reinforces their protective association against prosthetic joint infection and supports adherence to guideline-endorsed prophylaxis.

Abstract Objective: Suppressive antibiotic therapy (SAT) is used to prevent recurrent prosthetic joint infections (PJI) among patients who undergo debridement, antibiotics, and implant retention (DAIR). We aimed to assess SAT outcomes among younger, immunocompetent patients. Design: Retrospective cohort study. Patients: Immunocompetent patients <65 years of age who received DAIR for PJI of the hip, knee, or shoulder. Setting: Veterans Affairs hospitals. Methods: SAT was divided into short-term (oral antibiotics given for <3 months after guideline concordant therapy) and long-term SAT (>3 months to 5 years of oral antibiotics). The primary outcome was treatment failure (TF) and mortality combined. SAT was a time-dependent covariate in Cox proportional hazards models. Results: Of the 938 patients, 15% received short-term SAT, 20% received long-term SAT, and 65% did not receive SAT. Short- and long-term SAT were significantly associated with decreased hazards of TF or mortality (short-term SAT adjusted hazard ratio (aHR) = 0.27; 95% confidence interval (CI): 0.11, 0.67; Long-term SAT aHR = 0.52; 95% CI: 0.30, 0.89). Short-term SAT was significantly associated with C. difficile infection (aHR: 3.47; 95% CI: 1.38, 8.74). Short-term SAT (aHR: 7.83; 95% CI: 4.80, 12.77) and long-term SAT (aHR: 1.68; 95% CI: 1.19, 2.38) were significantly associated with antibiotic-associated diarrhea. Long-term SAT was not significantly associated with TF alone (aHR = 0.61; 95% CI: 0.32, 1.16). Conclusions: SAT was significantly associated with decreased death or TF and increased side effects. Benefits and risks must be weighed before prescribing SAT to younger, immunocompetent patients.

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.