Update of biomarkers to diagnose diabetic foot osteomyelitis: A meta-analysis and systematic review.

The aim of this study was to evaluate the diagnostic characteristics of biomarker for diabetic foot osteomyelitis (DFO). We searched PubMed, Scopus, Embase and Medline for studies who report serological markers and DFO before December 2022. Studies must include at least one of the following diagnostic parameters for biomarkers: area under the curve, sensitivities, specificities, positive predictive value, negative predictive value. Two authors evaluated quality using the Quality Assessment of Diagnostic Accuracy Studies tool. We included 19 papers. In this systematic review, there were 2854 subjects with 2134 (74.8%) of those patients being included in the meta-analysis. The most common biomarkers were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and procalcitonin (PCT). A meta-analysis was then performed where data were evaluated with Forrest plots and receiver operating characteristic curves. The pooled sensitivity and specificity were 0.72 and 0.75 for PCT, 0.72 and 0.76 for CRP and 0.70 and 0.77 for ESR. Pooled area under the curves for ESR, CRP and PCT were 0.83, 0.77 and 0.71, respectfully. Average diagnostic odds ratios were 16.1 (range 3.6-55.4), 14.3 (range 2.7-48.7) and 6.7 (range 3.6-10.4) for ESR, CRP and PCT, respectfully. None of the biomarkers we evaluated could be rated as 'outstanding' to diagnose osteomyelitis. Based on the areas under the curve, ESR is an 'excellent' biomarker to detect osteomyelitis, and CRP and PCT are 'acceptable' biomarkers to diagnose osteomyelitis. Diagnostic odds ratios indicate that ESR, CRP and PCT are 'good' or 'very good' tools to identify osteomyelitis.

The infected diabetic foot: Modulation of traditional biomarkers for osteomyelitis diagnosis in the setting of diabetic foot infection and renal impairment.

The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM-NSRI), and patients with diabetes and SRI (DM-SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM-NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM-SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM-NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM-SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient-specific factors when interpreting ESR results in the context of OM diagnosis.

Healing rates and outcomes following closed transmetatarsal amputations: A systematic review and random effects meta-analysis of proportions.

Transmetatarsal amputation (TMA) is a common surgical procedure for addressing severe forefoot pathologies, such as peripheral vascular disease and diabetic foot infections. Variability in research methodologies and findings within the existing literature has hindered a comprehensive understanding of healing rates and complications following TMA. This meta-analysis and systematic review aims to consolidate available evidence, synthesising data from multiple studies to assess healing rates and complications associated with closed TMA procedures. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search of Medline, Embase, and Cochrane databases was conducted for articles published from January 1st, 1988, to June 1st, 2023. Inclusion criteria comprised studies reporting healing rates in non-traumatic transmetatarsal amputation patients with more than 10 participants, excluding open TMAs. Two independent reviewers selected relevant studies, with disagreements resolved through discussion. Data extracted from eligible studies included patient demographics, healing rates, complications, and study quality. Among 22 studies encompassing 1569 transmetatarsal amputations, the pooled healing rate was 67.3%. Major amputation rates ranged from 0% to 55.6%, with a random-effects pooled rate of 23.9%. Revision rates varied from 0% to 36.4%, resulting in a pooled rate of 14.8%. 30-day mortality ranged from 0% to 9%, with a fixed-effects pooled rate of 2.6%. Post-operative infection rates ranged from 3.0% to 30.7%, yielding a random-effects pooled rate of 16.7%. Dehiscence rates ranged from 1.7% to 60.0%, resulting in a random-effects pooled rate of 28.8%. Future studies should aim for standardised reporting and assess the physiological and treatment factors influencing healing and complications.

Limited Clinical Utility of Routine Mycobacterial Cultures for the Management of Diabetic Foot Infections.

Mycobacterial infections of the foot and ankle are uncommon. In a cohort of 2340 patients with diabetic foot infection (DFI) in a region with increased prevalence of mycobacterial disease, we identified no clinically significant positive cultures over a 3-year period. Routine mycobacterial culture of DFIs is of limited clinical utility.

The infected diabetes-related foot: Comparison of erythrocyte sedementation rate/albumin and C-reactive protein/albumin ratios with erythrocyte sedimentation rate and C-reactive protein to differentiate bone and soft tissue infections.

The objective of this study was to evaluate the effectiveness of C-reactive protein (CRP)/albumin, erythrocyte sedimentation rate (ESR)/albumin ratio, ESR, CRP and albumin to differentiate bone and soft tissue infection in persons with diabetes. We retrospectively evaluated 242 individuals admitted to hospital with diabetes-related foot infections (DFI). We categorised DFI cases as either bone (OM) or soft tissue infection based on bone culture and/or histology. We evaluated the diagnostic accuracy of CRP, ESR, albumin, CRP/albumin and ESR/albumin as biomarkers to diagnose OM in persons with diabetes. The median age was 53 years (74% male). There were 224 diabetes-related patients of which 125 had been diagnosed with osteomyelitis. The ESR/albumin and CRP/albumin ratios cut-points were >17.84 and >1.83, respectively. ESR/albumin and CRP/albumin ratios had similar diagnostic parameters: AUC (0.71, 0.71), sensitivity (70.0%, 57.0%), specificity (62.0%, 75.0%), positive predictive value (67.0%, 71.0%) and negative predictive value (66.0% and 71.0%). In contrast diagnostic efficiency of CRP and ESR were AUC 0.71 and 0.71, sensitivity (45.6%, 71.2%), specificity (85.5%, 60.7%), positive predictive value (70.0%, 65.9%) and negative predictive value (59.5%, 66.4%), respectively. When comparing area under the curves, the results showed that ESR/albumin was not significantly different to ESR alone (Delong test pvs ESR >0.1). Similarly, CRP/albumin was not significantly different to CRP alone (Delong test pvs CRP >0.1). In conclusion, ESR/albumin and CRP/albumin ratios provided comparable results as using ESR and CRP alone.

Predictive Value of MRSA Nares Colonization in Diabetic Foot Infections: A Systematic Review and Bivariate Random Effects Meta-Analysis.

The primary objective of this study was to assess the negative predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs in MRSA diabetic foot infections. MEDLINE and Cochrane Library were searched from inception to May 1, 2020. The following search string was used: (methicillin-resistant S. aureus OR MRSA) AND (nasal OR nares) AND (diabetic OR foot OR diabetic foot infections). All studies that contained data comparing MRSA nasal swab positivity to wound cultures from diabetic foot infections and met the inclusion criteria were included. Among the 86 relevant studies, 6 studies with 8706 diabetic patients were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline extension for Diagnostic Test Accuracy reviews was followed. The primary meta-analysis outcomes were the negative and positive predictive values of MRSA nasal swabs for MRSA diabetic foot infections. The pooled specificity and pooled sensitivity were determined by generating hierarchical summary receiver characteristic operating curves. In the bivariate meta-analysis, involving the 6 studies, pooled sensitivity and specificity was 41.7% (95% confidence interval = 32.9, 51) and 94.1% (95% confidence interval = 89.5, 96.8), respectively. In low-moderate MRSA prevalence levels (<15%), negative predictive value of MRSA nasal swab was >90% and positive predictive value was <55%. This meta-analysis suggests that in patients with diabetic foot infections, the nasal swab MRSA screen has a poor positive predictive value but an excellent negative predictive value in regions of low to moderate prevalence of MRSA diabetic foot infections.

An Umbrella Systematic Review and Meta-Analysis of Systematic Reviews on the Topic of Foot and Ankle Arthrodesis Nonunion Rates.

The purpose of this systematic review and meta-analysis was to appraise and combine the available systematic reviews reporting nonunion incidence and prevalence in foot and ankle arthrodesis procedures. The Cochrane Library and MEDLINE were searched for relevant systematic reviews from inception to January 2022. Two independent reviewers selected and reviewed eligible studies. Studies were included if they were systematic reviews or meta-analyses reporting nonunion incidence and prevalence in foot or ankle arthrodesis procedures. Fourteen systematic reviews of 8 types of joint arthrodesis procedures were included for meta-analysis. These reviews comprised 138 studies with 5793 joint arthrodesis procedures. Quality of the included reviews were assessed using the AMSTAR2 checklist. Overall and subgroup meta-analysis of prevalence were performed using random effects model. Publication bias was determined by evaluation of a DOI plot with the Luis Furuya-Kanamori index of asymmetry. The pooled prevalence for foot and ankle nonunion rate was 8.1% (95% confidence interval [CI] 6.5%-9.9%). Overall prevalence of nonunion for single joint foot and ankle joint arthrodesis was 6.1% (95% CI 4.8%-7.6%). Subgroup analysis found that the highest rate of nonunion occurred during tibiotalocalcaneal arthrodesis with 27.1% (95% CI 19.4%-35.2%). We have reported the first meta-analysis of systematic reviews on nonunion rates in foot and ankle arthrodesis procedures. The overall nonunion rate for foot and ankle arthrodesis procedures was 8.1%. For single joint fusion procedures, the nonunion prevalence was 6.1%. Our reported nonunion rates are lower than previously published numbers.