The Effect of Limb Salvage Efforts in Different Age Groups: Relationships Between Major and Minor Amputations.

"Limb salvage" efforts, such as performing minor amputations before infections spread proximally from the foot to decrease major lower extremity amputation, are an important part of healthcare today. It is unclear whether these efforts are preventing the number of major amputations and improving patients' quality of life and the cost-effectiveness of the U.S. healthcare system. Rates of non-traumatic lower extremity amputation (NLEA) among patients with diabetes decreased in the early 2000s but rebounded in the 2010s. We analyzed the proportion of major amputations and differences in amputation rates between age groups in Texas. Patient data was extracted from the Texas Hospital Discharge Data Public Use Data File. Population estimates were obtained from the Texas Population Estimates Program from 2011 to 2015 and from intercensal estimates provided by the U.S. Census Bureau from 2006 to 2010. Raw numbers of minor, major, and all NLEA surgeries and the ratio of major amputations to total amputations per year were reported for each age group. Poisson regression and Joinpoint analyses were performed to capture these changes in trends. Rates of amputations increased, with significant decreasing relative prevalence of major amputations. Patients aged 45 to 64 with diabetes are likely driving these increases. Rates of lower extremity amputation in patients with diabetes increased from 2009 to 2015. This holds for all and minor amputations. In contrast, the ratio of major to all amputations decreased from 2010. Utilization of major and minor amputation differs between age groups, remaining stable in the youngest subjects, with minor amputation rates increasing in those aged 45 to 64.

A Model Study to Evaluate Osseointegration and Fracture Healing Following Open Reduction and Internal Fixation (ORIF) in Diabetic Lewis Rats.

There is a higher risk of implant osseointegration failure after open reduction and internal fixation (ORIF) in patients with diabetes due to increased inflammatory conditions, associated metallic corrosion and infection. While it is possible to avoid elective osseous surgery in patients with diabetes, it may not be the case in nonelective cases, such as ORIF ankle fractures. A total of 30 male Lewis rats (12-15 weeks old) were distributed into diabetic (D) and nondiabetic (ND) groups. Fracture healing and osseointegration were evaluated at 2-, 10-, and 21-day time points. Microtomographic and histological analysis depicted distinct differences in fracture healing and osseointegration between D and ND animals. Immunohistochemical analysis exhibited elevated proliferation (PCNA) and osteogenic (Runx2) cells for ND animals, while HMGB1 (inflammatory marker) was elevated for D animals during healing. Bone resorption marker CTX-1 was elevated in the plasma of D animals at 2 days, while bone formation marker P1NP was higher for ND animals at 10 days. Overall, this model resulted in delayed implant osseointegration and fracture healing in diabetic animals, highlighting the importance of developing new biomaterials or implant coatings that can improve bone healing outcomes in this patient population.

The Impact of Hospitalization for Diabetic Foot Infection on Health-Related Quality of Life: Utilizing PROMIS.

Diabetic foot infections (DFI) are an increasingly common cause of hospitalizations. Once hospitalized with DFI, many patients require some level of amputation, often undergoing multiple operations. With increasing importance on patient-centered metrics, self-reported health-related quality of life (HRQOL) tools have been developed. This prospective cohort study aimed assessed the impact of DFI on HRQOL. Two hundred twenty-four patients completed the 29-item Patient-Reported Outcome Measurement Information System (PROMIS) and 12-Item Short Form (SF-12) survey. Secondary outcomes using the Foot and Ankle Ability Measures survey were obtained and included in the analysis. The study group was comprised of hospitalized patients with DFIs (n = 120), and the control group was comprised of patients with diabetes who were evaluated for routine outpatient foot care (n = 104); diabetic foot screening, wound care, onychomycosis, and/or callosities. Using this cohort, a propensity score-matched sample of hospitalized patients with DFI (n = 35) and control group patients (n = 35) was created for comparative analysis. The 2-independent sample t test was used to test for group differences on each of the PROMIS subscale outcomes. Using PROMIS, we found that hospitalized patients with DFI reported significantly worse HRQOL in 6 of 7 subscales (physical function, anxiety, depression, fatigue, social role, pain intensity; p value range: .0001-.02) compared to outpatients with diabetes evaluated for routine foot care. There was no significant difference between the 2 groups on sleep disturbance (p = .22). Patients hospitalized for DFI report lower HRQOL compared to patients with diabetes receiving routine outpatient foot care.

Are the Sanders-Frykberg and Brodsky-Trepman Classifications Reliable in Diabetic Charcot Neuroarthropathy?

The purpose of this study was to assess the intra- and inter-reader reliability of the 2 Charcot neuroarthropathy classifications (Sanders-Frykberg and Brodsky-Trepman), as well as Eichenholtz staging. We hypothesized that the inter-reader reliability, with respect to these 3 classification systems, would be moderate at best. Digital radiographic images were organized in a digital slide presentation without clinical information. All 5 reviewers underwent a standard training session administered by the principal investigator, reviewing 5 cases of Charcot neuroarthropathy. Images of 55 cases of Charcot neuroarthropathy and 5 normal cases were distributed to each of the 5 physicians electronically, who independently rated all 60 cases according to the 3 classification systems. The 95% confidence interval of the intraclass correlation coefficient estimate for Sanders-Frykberg was 0.9601 to 0.9833 at week 0 and 0.9579 to 0.9814 at week 8, which can be regarded as "excellent" reliability. For Trepman-Brodsky, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.8463 to 0.9327 at week 0 and 0.8129 to 0.9226 at week 8, which can be regarded as "good" to "excellent" reliability. For Eichenholtz, the 95% confidence interval of the intraclass correlation coefficient estimate was 0.6841 to 0.8640 and 0.6931 to 0.8730 at weeks 0 and 8, respectively, which can be regarded as "moderate" to "good" reliability. The classification systems of Charcot neuroarthropathy are an important tool for communication among physicians. Based on the results at our institution, the Sanders-Frykberg classification exhibited the best inter-reader performance. The Trepman-Brodsky classification exhibited good to excellent reliability as well. The intraclass correlation coefficient of the Eichenholtz classification was moderate to good.

Magnetic Resonance Imaging of Diabetic Foot Osteomyelitis: Imaging Accuracy in Biopsy-Proven Disease.

Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO). The gold standard to diagnose osteomyelitis is bone biopsy with a positive culture and/or histopathology finding consistent with osteomyelitis. The purpose of this study is to assess the accuracy of MRI readings in biopsy-proven diabetic foot osteomyelitis with a second read done by a blinded, expert musculoskeletal radiologist. A retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large county hospital between 2010 and 2014. A second, blinded musculoskeletal radiologist reviewed the images for accuracy, once the official reading was recorded. Imaging results were correlated with the final diagnosis of osteomyelitis determined by bone biopsy. In 17 of 58 patients (29.3%), the diagnosis of DFO by MRI was not confirmed by bone biopsy. There were 12 false positives and 5 false negatives. After the second expert read, there were 5 false positives and 4 false negatives. The overall accuracy was 84% for the second read. Our study demonstrated results comparable to the previously reported meta-analysis findings. There is a clear variation on the read of MRI that could lead to an incorrect diagnosis of DFO. An integrated approach with evaluation of clinical findings, communication with radiologist about the MRI results when indicated, and bone biopsy is warranted for accurate diagnosis management of DFO.

Are Surrogate Markers for Diabetic Foot Osteomyelitis Remission Reliable?

BACKGROUND: We aimed to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections (DFIs). METHODS: Thirty-five patients with DFIs were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histologic analysis initially and for recurrence. Fisher exact and χ2 tests were used for dichotomous variables and Student t and Mann-Whitney U tests for continuous variables (α = .05). RESULTS: Twenty-four patients were diagnosed as having osteomyelitis and 11 as having soft-tissue infections. Four patients (16.7%) with osteomyelitis had reinfection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed as having osteomyelitis versus soft-tissue infections. There were no differences in osteomyelitis reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for DFIs at the same site (16.7% versus 36.4%; P = .20), amputation at the same site after discharge (12.5% versus 36.4%; P = .10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate of 8.3% to 20.8%. CONCLUSIONS: Most osteomyelitis markers were similar to markers in soft-tissue infection. Commonly reported surrogate markers were not shown to be specific to identify patients who failed osteomyelitis treatment compared with patients with soft-tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

Increased Risk of Nonunion and Charcot Arthropathy After Ankle Fracture in People With Diabetes.

The aim of this study was to evaluate the frequency of complications after an ankle fracture in patients with and without diabetes and to evaluate risk factors for nonunion. We conducted a retrospective study of 439 patients with ankle fractures (31.7% had diabetes) and followed them for 1 year or until the fracture healed. The fracture severity and determination of nonunion and Charcot arthropathy were determined from independent evaluation of radiographs by 2 members of the research team. Nonunion was defined as a fracture that did not heal within 6 months of the fracture. The majority of patients were women (67% in each group). The risk of complications was significantly higher in patients with diabetes compared with those without diabetes. The odds ratio (OR) and 95% confidence interval (CI) for nonunion was 6.5 (3.4 to 12.8); for Charcot arthropathy, 7.6 (2.3 to 21.0); for wounds, 1.8 (1.1 to 2.9); for infection, 2.8 (1.4 to 5.7); and for amputation, 6.6 (0.98 to 80.0). In the logistical regression analysis, 6 factors were associated with fracture nonunion: dialysis (7.7; 1.7 to 35.2), diabetes (3.3; 1.5 to 7.4), fracture severity (bi- and trimalleolar fractures) (4.9; 1.4 to 18.0), beta blockers (2.5; 1.1 to 5.4), steroids (3.1; 1.2 to 7.7), and infection (3.7; 1.2 to 11.3). The results of the study demonstrate the increased risk of complications after an ankle fracture among patients with diabetes, dialysis, or open fractures and those using steroids and beta blockers. Further work is needed to identify areas for risk reduction.

Does negative pressure wound therapy with irrigation improve clinical outcomes? A randomized clinical trial in patients with diabetic foot infections.

AIM: To compare the efficacy of Negative Pressure Wound Therapy (NPWT) with and without irrigation with 0.1% polyhexanide-betaine. METHODS: We randomized 150 subjects in a 16-week RCT to compare healing in patients with diabetic foot infections. NPWT delivered at 125 mm Hg continuous pressure. NPWT-I were administered at 30 cc per hour. RESULTS: There were no differences clinical treatment or outcomes: wound area after surgery (18.5 ± 19.0 vs. 13.4 ± 11.1 cm2, p = 0.50), duration of antibiotics (39.7 ± 21.0 vs. 38.0 ± 24.6 days, p = 0.40), number of surgeries (2.3 ± 0.67 vs. 2.2 ± 0.59, p = 0.85), duration of NPWT (148.1 ± 170.4 vs. 114.5 ± 135.1 h, p = 0.06), healed wounds (58.7% vs. 60.0%, p = 0.86), time to healing (56.3 ± 31.7 vs. 50.7 ± 27.8, p = 0.53), length of stay (13.8 ± 6.4 vs. 14.5 ± 11.2 days, p = 0.42), re-infection (20.0% vs. 22.7%, p = 0.69, and re-hospitalization (17.3% vs. 18.7, p = 0.83). CONCLUSIONS: The addition of irrigation to NPWT did not change clinical outcomes in patients with diabetic foot infections. CLINICAL TRIAL NUMBER: NCT02463487, ClinicalTrials.gov.

Clinical Outcomes of Foot Infections in Patients Without Diabetes.

The aim of this study was to report clinical outcomes of moderate and severe foot infections in patients without diabetes. Medical records of 88 nondiabetic patients with foot infections treated at a safety net hospital were retrospectively reviewed. Patients were grouped by the presence of soft-tissue infection (STI) or osteomyelitis (OM). The diagnosis of OM was determined by positive bone culture or histopathology. STIs were defined by negative bone biopsy or negative imaging with magnetic resonance imaging or computed tomography/dual-modality radiolabeled white blood cell single-photon emission computed tomography. Patient outcomes were recorded ≤1 year after admission. Eighty-eight nondiabetic patients admitted to our institution for moderate or severe foot infections were included, 45 OM and 43 STI. No differences were noted in patient characteristics except that OM patients had a higher prevalence of neuropathy (66.7% versus 39.5%, p = .02). OM patients required surgery more often (97.8% versus 67.4%, p < .01), a greater number of surgeries (2.0 ± 1.2 versus 1.4 ± 1.3, p = .02), and more amputations (75.6% versus 11.6%, p < .01) than STI patients. OM patients had a higher proportion of wounds that healed (82.2% versus 62.8%, p = .04). There were no significant differences in reinfection (35.6% versus 25.6%, p = .36), foot-related readmission to hospital (35.6% versus 23.3%, p = .25), or total duration of antibiotics (13.9 ± 10.2 versus 13.5 ± 12.9, p = .87) between OM and STI patients. In conclusion, OM patients required more surgeries and amputations than patients with STIs; however, they had similar rates of reinfection and readmission within a year after the index hospitalization.

Randomized clinical study to compare negative pressure wound therapy with simultaneous saline irrigation and traditional negative pressure wound therapy for complex foot infections.

The aim of this study was to compare the efficacy of different negative pressure wound therapy (NPWT) devices and NPWT with and without simultaneous irrigation in patients admitted to hospital with moderate and severe foot infections. Ninety patients were randomized in a 12-week prospective, randomized noninferiority trial to compare wound healing in patients with moderate and severe infected foot wounds treated with NPWT after surgery. Inclusion criteria included ABI > 0.5 or toe pressures >30 PVR/mmHg, >18 years of age and exclusion included active Charcot arthropathy, collagen vascular disease, HIV, and hypercoagulable state. We compared two different traditional devices, NPWT-K (KCI, VAC Ulta) and NPWT-C (Cardinal, PRO), and NPWT-I with saline irrigation (Cardinal, PRO). All patients had therapy delivered at 125 mmHg continuous pressure. In patients who received simultaneous saline irrigation (NPWT-I), the administration rate was 15 ml per hour. The primary outcome was the proportion of healed wounds in 12 weeks. Secondary outcomes included surgical wound closure, number of surgeries, length of stay, and time to wound healing. Continuous data was presented as mean ± standard deviation. Analysis of variance was used to compare continuous variables and chi-square to compare dichotomous variables with an alpha of 0.05. There were no differences in outcomes among NPWT-I, NPWT-C, and NPWT-K groups in proportion of healed wounds (63.3%, 50.0%, 46.7% p = 0.39), surgical wound closure (83.3%, 80.0%, 63.3%, p = 0.15), number of surgeries (2.0 ± 0.49, 2.4 ± 0.77, 2.4 ± 0.68, p = 0.06), length of stay (16.3 ± 15.7, 14.7 ± 7.4, 15.3 ± 10.5 days, p = 0.87), time to wound healing (46.2 ± 22.8, 40.9 ± 18.8, 45.9 ± 28.3 days, p = 0.78). We did not identify any significant differences in clinical outcomes or adverse events between patients treated with different NPWT devices or NPWT with and without irrigation.

The Infected Diabetic Foot: Re-evaluating the Infectious Diseases Society of America Diabetic Foot Infection Classification.

BACKGROUND: We provide evidence to revise the Infectious Diseases Society of America (IDSA) diabetic foot infection classification by adding a separate tier for osteomyelitis and evaluating if moderate and severe infection criteria improve the classification's ability to direct therapy and determine outcomes. METHODS: We retrospectively evaluated 294 patients with moderate and severe infections. Osteomyelitis was confirmed by bone culture or histopathology. Soft tissue infection (STI) was based on negative bone culture, magnetic resonance imaging, or single-photon emission computed tomography. We stratified STI and osteomyelitis using IDSA criteria for moderate and severe infections and compared outcomes and complications. RESULTS: Osteomyelitis patients had greater antibiotic duration (32.5 ± 46.8 vs 63.8 ± 55.1 days; P < .01), surgery frequency (55.5% vs 99.4%; P < .01), number of surgeries (2.1 ± 1.3 vs 3.3 ± 2.3; P < .01), amputations (26.3% vs 83.4%; P < .01), reinfection (38.0% vs 56.7%; P < .01), and length of stay (14.5 ± 14.9 vs 22.6 ± 19.0 days; P < .01). There were no differences in moderate and severe STI outcomes except for infection readmissions (46.2% vs 25.0%; P = .02), and acute kidney injury (31.2% vs 50.0%; P = .03). There were no differences in moderate and severe osteomyelitis except the number of surgeries (2.8 ± 2.1 vs 4.1 ± 2.5; P < .01) and length of stay (18.6 ± 17.5 vs 28.2 ± 17.7; P < .01). CONCLUSIONS: The IDSA classification better reflects outcomes if risk categories are stratified by STI or osteomyelitis and moderate and severe infections are not categorized separately.

Do SIRS Criteria Predict Clinical Outcomes in Diabetic Skin and Soft Tissue Infections?

The aim of this study was to assess whether systemic inflammatory response syndrome (SIRS) is correlated with outcomes in diabetic foot infections (DFIs). We retrospectively reviewed 137 diabetic patients admitted to the hospital with Infectious Diseases Society of America moderate and severe DFIs. We used SIRS criteria to define severe infection based on the presence of at least 2 of the following: heart rate >90 bpm, temperature >38°C or <36°C, respiratory rate >20 breaths per minute, and white blood cell count >12,000/mm3 or <4,000/mm3. Patients with severe DFI were significantly younger (median 49.6 versus 53.6 years, p = .04), less often had type 2 diabetes (88.6% versus 98.9%, p = .01), and less often had a history of previous amputation (15.9% versus 40.9%, p < .01). There were no differences in patients with severe infections defined by SIRS versus moderate infections in the need for surgery (47.7% versus 59.1%, p = .27), any amputation (20.5% versus 29.0%, p = .29), leg amputations (6.8% versus 7.5%, p = .88), duration of antibiotics (median ± standard deviation 34.1 ± 46.5 versus 31.9 ± 47.2 days, p = .47), or healing within 1 year (68.2% versus 66.7%, p = 1.00). Length of hospital stay was the only outcome variable that was significantly different in severe infections (median 12.7 ± 11.9 versus 7.8 ± 5.8 days, p = .02). Foot-related readmission was more common in moderate infections (46.2% versus 25.0%, p = .02). In conclusion, SIRS criteria for severe infections in diabetic patients with skin and soft tissue infections were not associated with a difference in outcomes other than longer hospital stay.

Outcomes of Foot Infections Secondary to Puncture Injuries in Patients With and Without Diabetes.

It is difficult to compare foot infections in patients with diabetes to those without diabetes because foot infections are uncommon in people without diabetes. The aim of this study is to compare clinical outcomes in people with and without diabetes admitted to the hospital for an infected puncture wound. We evaluated 114 consecutive patients from June 2011 to March 2019 with foot infection resulting from a puncture injury; 83 had diabetes and 31 did not have diabetes. We evaluated peripheral arterial disease (PAD), sensory neuropathy, the need for surgery and amputation, length of hospitalization, and presence of osteomyelitis. Patients with diabetes were 31 times more likely to have neuropathy (91.6% versus 25.8%, p < .001, confidence interval [CI] 10.2 to 95.3), 8 times more likely to have PAD (34.9% versus 6.5%, p = .002, CI 1.7 to 35), and 7 times more likely to have kidney disease (19.3% versus 3.2%, p < .05, CI 0.9 to 56.5). They also took longer before presenting to the hospital (mean 20.1 ± 36.3 versus 18.8 ± 34.8 days, p = .09, CI 13 to 26.5); however, this result was not statistically significant. Patients with diabetes were 9 times more likely to have osteomyelitis (37.3% versus 6.5%, p = .001, CI 1.9 to 38.8). In addition, they were more likely to require surgery (95% versus 77%, p < .001, CI 1.6 to 21.4), required more surgeries (2.7 ± 1.3 versus 1.3 ± 0.8, p < .00001, CI 2.1 to 2.5), were 14 times more likely to have amputations (48.2% versus 6.5%, p < .0001, CI 3.0 to 60.2), and had 2 times longer hospital stays (16.2 ± 10.6 versus 7.5 ± 9 days, p = .0001, CI 11.9 to 15.9. Infected puncture wounds in patients with diabetes often fair much worse with more detrimental outcomes than those in patients without diabetes.

Erbium: Yttrium Aluminum Garnet Laser Accelerates Healing in Indolent Diabetic Foot Ulcers.

The objective of the study was to evaluate the effect of the erbium:yttrium aluminum garnet (YAG) laser on diabetic foot ulcers (DFUs) that had not responded to standard care. We retrospectively evaluated 22 nonhealing DFUs that received at least 4 weeks of standard wound care, demonstrated poor healing response, and subsequently were treated with an erbium:YAG laser. We measured the percent wound area reduction (PWAR) for the 4 weeks before initiating laser therapy and the PWAR for 4 weeks after the initiation of laser therapy. Erbium:YAG laser treatment consisted of 2 components: debridement and resurfacing. The laser settings were the same for all treatments. We used the paired t test to compare pretreatment with posttreatment wound area reduction. During the 4-week period before the initiation of laser therapy, the average PWAR was -33.6%. Four weeks after initiating treatment with the erbium:YAG laser, the average PWAR was 63.4% (p = .002) and 72.7% of wounds had ≥50% PWAR. By 12 weeks, 50% of wounds had healed. Erbium:YAG laser therapy accelerated DFU healing in a cohort of patients with ulcers that had been unresponsive to standard of care therapy.

What are the Optimal Cutoff Values for ESR and CRP to Diagnose Osteomyelitis in Patients with Diabetes-related Foot Infections?

BACKGROUND: Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined. QUESTIONS/PURPOSES: (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection? METHODS: The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations. RESULTS: An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67-80) and specificity of 56% (95% CI, 48-63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41-57) and specificity of 80% (95% CI, 74-86). If the ESR is < 30 mm/h, the likelihood of osteomyelitis is low. However, if ESR is > 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered. CONCLUSIONS: While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging. LEVEL OF EVIDENCE: Level III, diagnostic study.

The Effect of Withholding Antibiotics Prior to Bone Biopsy in Patients With Suspected Osteomyelitis: A Meta-analysis of the Literature.

OBJECTIVE: The aim of this meta-analysis is to evaluate the effect of withholding antibiotics prior to obtaining a bone biopsy in the diagnosis of osteomyelitis. METHODS: Literature searches on Scopus, PubMed, and Google Scholar were performed with the input antibiotic, bone, biopsy, osteomyelitis, and prior both separately and together, though initially as a combination, as key words for all study types in the English language published up until July 2018. The initial combination search (and subsequent additional search of the references) yielded 924 related articles, which ultimately resulted in 12 articles with adequate data for analysis. Data were analyzed using an inverse variance method to determine the weight of the studies in a random effects model, pooling the data for odds ratios (OR) and heterogeneity. Bias risk was determined with the Quality Assessment of Diagnostic Accuracy Studies 2 system. RESULTS: Of the 12 studies, 8 failed to demonstrate that antibiotics administered prior to bone biopsy have an effect on culture yield, while 4 reported a significant effect on culture yield. The total weighted OR for all studies was 2.02 (95% confidence interval [CI], 0.94-4.36; P = .04) and the prediction interval was 0.17-23.63. When vertebral osteomyelitis (VO) and nonvertebral osteomyelitis (NVO) articles were evaluated separately, the VO OR was 2.95 (95% CI, 1.40-6.24) and the prediction interval was 0.40-21.53. The OR for NVO was 0.66 (95% CI, 0.04-12.03) and the prediction interval was 0-114.53. CONCLUSIONS: When all studies as well as when NVO studies only were evaluated, there was no significant difference in bacterial pathogen yield based on antibiotic exposure. When VO studies were evaluated separately, there were fewer pathogens recovered than when antibiotics were administered prior to obtaining bone cultures.

Are We Misdiagnosing Diabetic Foot Osteomyelitis? Is the Gold Standard Gold?

To compare the incidence of osteomyelitis based on different operational definitions using the gold standard of bone biopsy, we prospectively enrolled 35 consecutive patients who met the criteria of ≥21 years of age and a moderate or severe infection based on the Infectious Diseases Society of America classification. Bone samples were obtained from all patients by percutaneous bone biopsy or intraoperative culture if the patient required surgery. Bone samples were analyzed for conventional culture, histology, and 16S ribosomal RNA genetic sequencing. We evaluated 5 definitions for osteomyelitis: 1) traditional culture, 2) histology, 3) genetic sequencing, 4) traditional culture and histology, and 5) genetic sequencing and histology. There was variability in the incidence of osteomyelitis based on the diagnostic criteria. Traditional cultures identified more cases of osteomyelitis than histology (68.6% versus 45.7%, p = .06, odds ratio [OR] 2.59, 95% confidence interval [CI] 0.98 to 6.87), but the difference was not significant. In every case that histology reported osteomyelitis, bone culture was positive using traditional culture or genetic sequencing. The 16S ribosomal RNA testing identified significantly more cases of osteomyelitis compared with histology (82.9% versus 45.7%, p = .002, OR 5.74, 95% CI 1.91 to 17.28) and compared with traditional cultures but not significantly (82.9% versus 68.6%, p = .17, OR 2.22, 95% CI 0.71 to 6.87). When both histology and traditional culture (68.6%) or histology and genetic sequencing cultures (82.9%) were used to define osteomyelitis, the incidence of osteomyelitis did not change. There is variability in the incidence of osteomyelitis based on how the gold standard of bone biopsy is defined in diabetic foot infections.

Lower Extremity Necrotizing Fasciitis in Diabetic and Nondiabetic Patients: Mortality and Amputation.

Lower extremity necrotizing fasciitis (NF) is a severe infection requiring immediate surgery. The aim of this study was to assess patient factors predictive of amputation and mortality in diabetes mellitus (DM) and non-DM patients with lower extremity NF. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was reviewed retrospectively. Out of 674 patients with lower extremity NF, 387 had DM (57.4%). Patients with DM had lower mortality (P = .004). Increased mortality was independently associated with age >60 years (adjusted odds ratio [aOR] = 3.96, 95% confidence interval [CI] = 1.69-9.77), partial thromboplastin time >38 seconds (aOR = 2.66, 95% CI = 1.09-6.62), albumin <2.0 mg/dL (aOR = 2.84, 95% CI = 1.13-7.37), coagulopathy (aOR = 3.29, 95% CI = 1.24-9.19), higher anesthesia risk category (aOR = 3.08, 95% CI = 1.18, 8.59), chronic obstructive pulmonary disease (aOR = 3.46, 95% CI = 1.13-10.9), postoperative acute respiratory distress syndrome (aOR = 5.24, 95% CI = 2.04-14.4), and postoperative septic shock (aOR = 5.14, 95% CI = 1.94-14.1). Amputation was independently associated with DM (aOR = 4.35, 95% CI = 2.63-7.35) but not mortality. Although DM was associated with more amputations for lower extremity NF, patients with DM had lower mortality than non-DM patients in the bivariate analysis. Further research is needed to investigate outcomes among DM and non-DM patients in the context of lower extremity NF.

Percutaneous CT guided bone biopsy for suspected osteomyelitis: Diagnostic yield and impact on patient's treatment change and recovery.

AIM: To evaluate the utility of percutaneous CT guided bone biopsy (PCBB) for suspected osteomyelitis (OM) and its eventual impact on patient management and recovery. MATERIAL AND METHODS: Patients who received a PCBB for suspected osteomyelitis from years 2012-2018. Patient demographics, lesion location, ulcer grade, signs of toxemia, serology, wound and blood cultures, bone biopsy and cross-sectional imaging results were recorded. Diagnostic yield of the bone biopsy and its role in influencing the final treatment plan and patient recovery were evaluated. Chi-square test was used. P-value less than 0.05 was considered statistically significant. RESULTS: 115 patients with mean age 50.86 ± 14.49 years were included. The common locations were sacrum/ischium (49/115, 43%) and spine (35/115, 30%). Clinically, 40/115 (35%) had toxemia and 67/115 (58%) had ulcers. Per serology, 17/111 (15%), 95/106 (90%), and 86/98 (88%) had an elevated WBC, CRP, and sedimentation rate, respectively. 22/91 (24%) had a positive blood culture and all 23/23 had a positive wound culture. On imaging, definitive and possible OM were reported in 84.1% and 14.2%, respectively, with 1.8% as no OM. Only 24/115 (21%) had a positive bone biopsy culture and only 10/24 (42%) total positive bone cultures impacted the treatment plan. There was no significant effect of antibiotics on the diagnostic yield of culture (p = 0.08). No statistical significance was found when comparing treatment change based on bone culture results versus all other factors combined (p = 0.33), or when comparing clinical improvement with and without positive bone cultures (p = 0.12). CONCLUSION: Despite positive cross-sectional imaging findings of OM, bone biopsy yield of positive culture is low, and it leads to a small impact in changing the treatment plan or altering the course of patient recovery.

Diagnostic Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein in Osteomyelitis of the Foot in Persons Without Diabetes.

The aim of the study was to assess the diagnostic value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in differentiating foot osteomyelitis (OM) from soft tissue infection (STI) in persons without diabetes. We evaluated 102 patients in a retrospective cohort study of nondiabetic patients admitted to our institution with OM (n = 51) and with STI (n = 51). Patient diagnosis was determined through bone culture and/or histopathology for OM and magnetic resonance scan and/or single-photon emission computed tomography for STI. Cutoffs for ESR and CRP to predict OM as identified by receiver operating characteristic were 45.5 mm/h and 3.45 mg/dL, respectively. The ESR cutoff demonstrated a sensitivity and specificity of 49% and 79%, while the values for CRP were 45% and 71%, respectively. The combined sensitivity and specificity for ESR and CRP were 33% and 84%. The positive and negative predictive values were 68% and 60% for ESR and 61% and 56% for CRP, respectively. In conclusion, ESR and CRP demonstrate poor sensitivity and specificity for detecting OM in the nondiabetic foot. These markers have little diagnostic utility in the nondiabetic foot.