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.

The infected diabetic foot: Analysis of diabetic and non-diabetic foot infections.

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year.

MRSA infection, re-infection and clinical outcomes in diabetic foot infections.

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.

Near-infrared spectroscopy data for foot skin oxygen saturation in healthy subjects.

Our objective was to evaluate normative data for near-infrared spectroscopy (NIRS) in 110 healthy volunteers by Fitzpatrick skin type (FST) and region of the foot. We obtained measurements of the dorsum and plantar foot using a commercially available device (SnapshotNIR, Kent Imaging, Calgary Canada). On the dorsum of the foot, people with FST6 had significantly lower oxygen saturation compared to FST1-5 (p < 0.001), lower oxyhaemoglobin compared to FST2-5 (p = 0.001), but there was no difference in deoxyhaemoglobin. No differences were found on the plantar foot. When comparing dorsal and plantar foot, there was higher oxyhaemoglobin (0.40 ± 0.09 vs. 0.51 ± 0.12, p < 0.001) and deoxyhaemoglobin (0.16 ± 0.05 vs. 0.21 ± 0.05, p < 0.001) on the plantar foot, but no differences in oxygen saturation (dorsal 70.7 ± 10.8, plantar 70.0 ± 9.5, p = 0.414). In 6.4% of feet, there were black areas, for which no NIRS measurements could be generated. All areas with no data were on the dorsal foot and only found in FST 5-6. People with FST6 had significantly larger areas with no data compared to FST 5 (22.2 cm2 ± 20.4 vs. 1.9 cm2 ± 0.90, p = 0.007). These findings should be considered when using NIRS technology. Skin pigmentation should be evaluated in future NIRS studies.

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.

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.

Medical mythology, misconceptions, and misinformation: does iodine impede wound healing?

INTRODUCTION: PI has been shown to be effective against a broad spectrum of bacteria and to be cytotoxic to a variety of cell types. Such findings led to the widespread belief that PI interferes with wound healing. OBJECTIVE: This article reviews laboratory studies, animal wound studies, and clinical studies that examine the efficacy and safety of iodine-based wound products in wound healing. METHODS: The authors searched PubMed and Scopus databases without time restrictions, and 62 articles were selected for complete evaluation. Fourteen RCTs and 5 comparative studies that evaluated PI and 15 RCTs that evaluated CI were included. RESULTS: In 63% (n = 12) of the PI studies, there was no difference between PI and controls and in 5% (n = 1) PI performed significantly better than the comparator. In 31% (n = 6), outcomes were better with controls than with PI. In the RCTs on CI, 64% (n = 9) of the studies found no difference between CI and controls. Thirty-five percent (n = 5) showed significantly positive influence of CI compared with controls. CONCLUSIONS: Both CI and PI appear to be safe, with no evidence that these products impede wound healing, are associated with more infections, or require more amputations compared with other modalities. PI can effectively be used for short periods of time, and CI is an effective wound care modality for chronic wounds.

Mönckeberg's Medial Calcific Sclerosis Makes Traditional Arterial Doppler's Unreliable in High-Risk Patients with Diabetes.

OBJECTIVE: To assess Mönckeberg's medial calcific sclerosis (MMCS) severity in patients with a diabetic foot infection. METHODS: This was an analysis of 2 randomized clinical trials in which we evaluated the treatment of 233 patients admitted to the hospital for moderate and severe foot infections. Arterial calcification was defined as visible radiopaque arteries on foot and ankle radiographs, recorded as the most distal visible artery involved (toes, metatarsals, and ankle/hindfoot). RESULTS: Most subjects (57.1%, n = 133) had MMCS, with extension to toes in 79 (59.4%), to metatarsals in 32 (24.1%), and to ankle/hindfoot in 22 patients (16.5%). In 7 patients (5.2%) MMCS was solely seen in dorsalis pedis (DP) artery, in 13 patients (9.8%) in posterior tibialis (PT) artery, and in 113 patients (85.0%) MMCS was seen in both arteries. Only 29.2% (n = 68) of DP arteries and 34.8% (n = 81) of PT arteries were not compressible by Doppler. DP and PT arteries were not compressible more often in MMCS (DP 34.3% vs 20.4%, P = .02 and PT 43.1% vs 21.4%, P < .01), toe-brachial indices of ≥0.7 were significantly more common in people without MMCS (46.0% vs 67.4%, P < .01). In contrast, there were no differences in skin perfusion pressure measurements (>50 mmHg; 67.7% vs 68.0%, P = .96), waveforms (biphasic/triphasic 83.5% vs 77.0%, P = .22), and pulse volume recording (9.6 ± 3.3 vs 13.7 ± 36.0) between patients with and without MMCS. CONCLUSION: MMCS is common in patients with diabetic foot infections. MMCS is associated with noncompressible arterial Doppler studies and likely interferes with the accuracy of arterial Doppler studies.

Mönckeberg's medial calcific sclerosis in diabetic and non-diabetic foot infections.

The aim of this study was to evaluate the prevalence and extent of lower extremity Mönckeberg's Medial Calcific Sclerosis (MMCS) in patients with and without diabetes in patients admitted to the hospital for foot infections. This study retrospectively reviewed 446 patients admitted to the hospital with a moderate or severe foot infection. We defined diabetes based on ADA criteria and reviewed electronic medical records for demographics, medical history and physical examination data. Anterior-posterior and lateral foot radiographs were examined to identify the presence and extent of vascular calcification. We categorised MMCS based on anatomical location: ankle joint to the navicular-cuneiform joint, Lis Franc joint to metatarsophalangeal joints and distal to the metatarsophalangeal joints. The prevalence of MMCS was 40.6%. The anatomic extent of MMCS was 19.3% in the toes, 34.3% in the metatarsals and 40.6% in the hindfoot/ankle. Calcification was not common solely in the dorsalis pedis artery (DP) (3.8%) or solely in the posterior tibial artery (PT) (7.0%). Usually, both DP and PT arteries were affected by MMCS (29.8%). The prevalence of MMCS was higher in people with diabetes (in hindfoot and ankle [50.1% vs. 9.9%, p ≤ 0.01]; metatarsals [42.6% vs. 5.9%, p ≤ 0.01]; and toes [23.8% vs. 4.0%, p ≤ 0.01]). People with diabetes were 8.9 (CI: 4.5-17.8) times more likely to have MMCS than those without diabetes. This is a group that often has poor perfusion and needs vascular assessment. The high prevalence of MMCS raises questions about the reliability of the conventional segmental arterial Doppler studies to diagnose PAD.

Supra- and Infra-Renal Aortic Neck Diameter Increase after Endovascular Repair of a Ruptured Abdominal Aortic Aneurysm.

Hypovolemia-induced hypotension may lead to an aortic diameter decrease in patients with a ruptured abdominal aortic aneurysm (rAAA). This study investigates the changes in supra- and infra-renal aortic neck diameters before and after endovascular aortic aneurysm repair (EVAR) for rAAA and the possible association with endograft apposition. A retrospective cohort study was conducted including 74 patients treated between 2010 and 2019 in two large European vascular centers. Outer-to-outer wall diameters were measured at +40, +10, 0, −10, and −20 mm relative to the lowest renal artery baseline on the last pre- and first post-EVAR computed tomography angiography (CTA) scan in a vascular workstation. Endograft apposition was determined on the first post-EVAR CTA scan. The post-operative diameter was significantly (p < 0.001) larger than the preoperative diameter at all aortic levels. The aortic diameter at +40 mm (supra-renal) and −10 mm (infra-renal) increased by 6.2 ± 7.3% and 12.6 ± 9.8%, respectively. The aortic diameter at +40 mm increased significantly more in patients with low preoperative systolic blood pressure (<90 mmHg; p = 0.005). A shorter apposition length was associated with a higher aortic diameter increase (R = −0.255; p = 0.032). Hypovolemic-induced hypotension results in a significant decrease in the aortic diameter in patients with an rAAA, which should be taken into account when oversizing the endograft.