The correlation between serum calcium levels and prognosis in patients with severe acute osteomyelitis.

Objective: To explore the relationship between serum calcium levels and the prognosis of severe acute osteomyelitis, and to assess the effectiveness of calcium levels in prognostic evaluation. Methods: Relevant patient records of individuals diagnosed with severe acute osteomyelitis were obtained for this retrospective study from the Medical Information Mart for Intensive Care (MIMIC-IV). The study aimed to assess the impact of different indicators on prognosis by utilizing COX regression analysis. To enhance prognostic prediction for critically ill patients, a nomogram was developed. The discriminatory capacity of the nomogram was evaluated using the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve, in addition to the calibration curve. Result: The study analyzed a total of 1,133 cases of severe acute osteomyelitis, divided into the survivor group (1,025 cases) and the non-survivor group (108 cases). Significant differences were observed between the two groups in terms of age, hypertension, sepsis, renal injury, and various laboratory indicators, including WBC, PLT, Ca2+, CRP, hemoglobin, albumin, and creatinine (P<0.05). However, no significant differences were found in race, gender, marital status, detection of wound microbiota, blood sugar, lactate, and ALP levels. A multivariate COX proportional hazards model was constructed using age, hypertension, sepsis, Ca2+, creatinine, albumin, and hemoglobin as variables. The results revealed that hypertension and sepsis had a significant impact on survival time (HR=0.514, 95% CI 0.339-0.779, P=0.002; HR=1.696, 95% CI 1.056-2.723, P=0.029). Age, hemoglobin, Ca2+, albumin, and creatinine also showed significant effects on survival time (P<0.05). However, no statistically significant impact on survival time was observed for the other variables (P>0.05). To predict the survival time, a nomogram was developed using the aforementioned indicators and achieved an AUC of 0.841. The accuracy of the nomogram was further confirmed by the ROC curve and calibration curve. Conclusion: According to the findings, this study establishes that a reduction in serum calcium levels serves as a distinct and standalone predictor of mortality among individuals diagnosed with severe acute osteomyelitis during their stay in the Intensive Care Unit (ICU) within a span of two years.

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.

Serum Calcium Level Combined with Platelet Count May Be Useful Indicators for Assisted Diagnosis of Extremity Posttraumatic Osteomyelitis: A Comparative Analysis.

BACKGROUND: A previous study had reported that patients with osteomyelitis (OM) appeared to be more likely to develop hypocalcemia before and after surgery. Calcium sulfate (CS) is frequently used as a local antibiotic vehicle in the treatment of OM, which may also affect serum calcium level. However, whether changes of serum calcium level are caused by OM and/or local use of calcium sulfate remains unclear. Also, platelet (PLT) count plays a crucial predictive role in periprosthetic joint infections (PJIs), but its role in assisted diagnosis of OM is largely unknown. The purpose of this study was to determine whether serum calcium level and PLT count may be helpful in assisted diagnosis of PTOM. METHODS: Between January 2013 and December 2018, we analyzed 468 consecutive patients (392 males and 76 females), including 170 patients with posttraumatic OM (PTOM), 130 patients with aseptic bone nonunion (ABN), and 168 patients recovered from fractures with requirement of implant removal set as controls. Preoperative serological levels of calcium, phosphorus, and PLT were detected, and comparisons were conducted among the above three groups. Additionally, correlations and receiver operating characteristic (ROC) curves were displayed to test whether calcium level and PLT can differentiate patients with ABN and PTOM. RESULTS: Outcomes showed that the incidences of asymptomatic hypocalcemia (PTOM vs. ABN vs. controls = 22.94% vs. 6.92% vs. 8.82%, χ 2 = 21.098, P < 0.001) and thrombocytosis (PTOM vs. ABN vs. controls = 35.3% vs. 13.84% vs. 12.35%, χ 2 = 28.512, P < 0.001) were highest in PTOM patients. Besides, the mean serological levels of phosphorus in PTOM and ABN patients were significantly higher than those in the controls (P = 0.007). The Area Under the Curve (AUC) of the ROC curve outcomes revealed that, with the combination of serum calcium level with PLT count, the predictive role was acceptable (AUC 0.730, P < 0.001, 95% CI 0.681-0.780). Also, serological levels of calcium of 2.225 mmol/L and PLT count of 246.5 × 109/L were identified as the optimal cut-off values to distinguish patients with and without PTOM. However, age- and gender-related differences in serum calcium levels (age, P = 0.056; gender, P = 0.978) and PLT count (age, P = 0.363; gender, P = 0.799) were not found to be statistically significant in any groups. In addition, no significant correlations were identified between serum calcium level and PLT count (R = 0.010, P = 0.839). CONCLUSIONS: Asymptomatic hypocalcemia and thrombocytosis appeared to be more frequent in this cohort with PTOM. Serological levels of calcium and PLT count may be useful biomarkers in screening patients suspected of PTOM.

Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers.

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1ß, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.

Children with Primary Septic Arthritis Have a Markedly Lower Risk of Adverse Outcomes Than Those with Contiguous Osteomyelitis.

BACKGROUND: It is widely believed that septic arthritis poses a risk of joint destruction and long-term adverse outcomes for children if not treated emergently. In the present study, children who had primary confirmed septic arthritis were compared with those who had septic arthritis and adjacent osteomyelitis to evaluate differences that affect the relative risk of adverse outcomes. METHODS: Children who underwent multidisciplinary treatment for septic arthritis with or without contiguous osteomyelitis between 2009 and 2019 were retrospectively studied. Clinical, laboratory, treatment, and outcome data were compared between cohorts of children with primary confirmed septic arthritis and children with septic arthritis and contiguous osteomyelitis. RESULTS: One hundred and thirty-four children had primary confirmed septic arthritis, and 105 children had septic arthritis with contiguous osteomyelitis. Children with osteomyelitis were older (median, 7.4 versus 2.4 years), had higher initial C-reactive protein (median, 15.7 versus 6.4 mg/dL), and had a higher rate of thrombocytopenia (21.0% versus 1.5%). They also had a higher rate of bacteremia (69.5% versus 20.2%) for a longer duration (median, 2.0 versus 1.0 days). Detected pathogens in children with osteomyelitis as compared with those with primary septic arthritis were more likely to be Staphylococcus aureus (77.1% versus 32.1%) and less likely to be Kingella kingae (2.9% versus 32.1%). Children with contiguous osteomyelitis had longer hospitalizations (median, 8.0 versus 4.0 days), a higher rate of intensive care (21.0% versus 1.5%), a higher readmission rate (17.1% versus 5.2%), and a higher complication rate (38.1% versus 0.7%). CONCLUSIONS: Primary septic arthritis in children is dissimilar to septic arthritis associated with osteomyelitis. The present study demonstrates that long-term adverse outcomes in children with septic arthritis are likely due to the contiguous osteomyelitis. Children with primary septic arthritis are sufficiently distinguishable from those who have contiguous osteomyelitis to guide decisions for magnetic resonance imaging acquisition, duration of antibiotic therapy, and length of outpatient follow-up in order to recognize and address adverse outcomes. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cytokine profile in patients with chronic non-bacterial osteomyelitis, juvenile idiopathic arthritis, and insulin-dependent diabetes mellitus.

OBJECTIVES: Our study aimed to evaluate the cytokine levels in pediatric chronic non-bacterial osteomyelitis (CNO) patients and compare these with other immune-mediated diseases and healthy controls. METHODS: In this prospective study, we included 42 children with CNO, 28 patients with non-systemic juvenile idiopathic arthritis (JIA), 17 children with insulin-dependent diabetes mellitus (IDDM), and 30 healthy age-matched controls. In each of the CNO patients and comparison groups, the levels of 14-3-3-η protein, S100A8/A9 protein, interleukin-4 (IL-4), interleukin-17 (IL-17), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) were measured by ELISA assay. RESULTS: All studied cytokines in the CNO patients were significantly higher than controls, and IDDM, 14-3-3-η protein, IL-18, IL-4, IL-17, IL-1ß, and TNF-α were less than in JIA patients. In the discriminant analysis, ESR, 14-3-3 protein, S100A8/A9, IL-18, IL-4, and TNF-α can discriminate CNO from JIA, and 14-3-3 protein, S100A8/A9, IL-18, IL-17, IL-4, and TNF-α can distinguish CNO from other diseases and HC. CONCLUSION: The increased level of pro-inflammatory cytokines confirms the role of monocyte-driven inflammation in CNO patients. Cytokines may prove valuable as biomarkers and potential therapeutic targets for CNO.

Distinct expression trend of signature antigens of Staphylococcus aureus osteomyelitis correlated with clinical outcomes.

The major limitations of clinical outcome predictions of osteomyelitis mediated by Staphylococcus aureus (S. aureus) are not specific and definitive. To this end, current studies aim to investigate host immune responses of trend changes of the iron-regulated surface determinant (Isd) of IsdA, IsdB, IsdH, cell wall-modifying proteins of amidase (Amd) and glucosaminidase (Gmd), and secreted virulence factor of chemotaxis inhibitory protein S. aureus (CHIPS) and staphylococcal complement inhibitor (SCIN) longitudinally to discover their correlationship with clinical outcomes. A total of 55 patients with confirmed S. aureus infection of the long bone by clinical and laboratory methods were recruited for the study. Whole blood was collected at 0, 6, 12 months for the serum that was used to test IsdA, IsdB, IsdH, Gmd, Amd, CHIPS, and SCIN using a customized Luminex assay after clinical standard care parameters were collected. The patients were then divided into two groups: (1) infection controlled versus (2) adverse outcome based on clinical criteria for statistical analysis. We found that standard clinical parameters were unable to distinguish therapeutic outcomes. Significant overexpression of all antigens was confirmed in infection patients at 0-, 6-, and 12-month time points. A distinct expression trend and dynamic changes of IsdB, Amd, Gmd, and CHIPS were observed between infection controlled and adverse outcome patients, while the IsdA, IsdH, SCIN remained demonstrated no statistical significance. We conclude that dynamic changes of specific antigens could predict clinical outcomes of S. aureus osteomyelitis. Clinical Relevance: The trend changes of host immune responses to S. aureus specific antigens of IsdB, Gmd, Amd, and CHIPS could predict clinical outcomes of S. aureus osteomyelitis.

Treatment of Chronic Hematogenous Osteomyelitis in Children With Antibiotic Impregnated Calcium Sulphate.

BACKGROUND: The purpose of this study was to evaluate the clinical and radiologic outcome of chronic hematogenous osteomyelitis (CHOM) in children, treated with single-stage debridement and dead space management using antibiotic impregnated calcium sulphate pellets. METHODS: The authors retrospectively evaluated a consecutive series of 34 patients who presented with CHOM from 2011 to 2017. In each case, CHOM was classified according to the Beit CURE classification. Following thorough surgical debridement, the resulting dead space in the bone was filled with the antibiotic impregnated beads before primary closure. RESULTS: Of the 31 patients available for follow up, effective regeneration of bone was confirmed in all cases, with radiographic bone healing typically observed at around 12 weeks. None of the children required reoperation for infection and none had recurrence of infection at the time of final review. The beads were completely absorbed within 3 months. No systemic adverse reactions to the local delivery of antibiotics were observed in this study. CONCLUSIONS: The authors found that single-stage debridement in conjunction with antibiotic impregnated calcium sulphate was an effective means of treating CHOM in children, with effective eradication of infection in every case. LEVEL OF EVIDENCE: Level IV-Retrospective case series. See instructions for authors for a complete description of levels of evidence.

External Validation of an Algorithm to Predict Adjacent Musculoskeletal Infection in Pediatric Patients With Septic Arthritis.

BACKGROUND: Septic arthritis (SA) remains a potentially morbid disease in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive tool for recognizing associated osteomyelitis and intramuscular abscess, but is a limited resource. The aim of this study is to externally validate a previously developed algorithm (Rosenfeld and colleagues) to predict adjacent infection in pediatric patients diagnosed with SA. METHODS: We identified 120 children under 16 with presumed SA presenting to a tertiary referral center between 2008 and 2018. Patients without confirmed SA, those with insufficient data, and patients who did not receive perioperative MRI were excluded, leaving 53 patients. The previous algorithm suggests that patient age (above 4 y), C-reactive protein (>8.9 mg/L), platelet count (<310×10cells/µL), duration of symptoms (>3 d), and absolute neutrophil count (>7.2×10cells/µL) are risk factors for adjacent infection, with 3 or more variables signifying a "positive" result. Comparing against the gold standard of MRI, the accuracy of the algorithm was validated in terms of sensitivity, specificity, likelihood ratio (LR), and positive and negative predictive value. Discrimination and calibration of this algorithm have been assessed using receiver operating curve analysis and calibration plots. RESULTS: The sensitivity and specificity of criteria from Rosenfeld algorithm were 73% and 44%, respectively. Receiver operating curve showed poor discrimination [area under the curve=0.54, confidence interval (CI): 0.26-0.83]. The positive predictive value was 55.9% and the negative predictive value was 63.1% with LR +1.23 (CI: 0.87-1.98) and LR -0.61 (CI 0.28-1.30). Only 53% of patients with 4 or more criteria had an adjacent infection on MRI. Examining our cohort, children with a positive MRI finding had higher mean C-reactive protein (77 vs. 122 mg/L, P=0.04) and were more likely to have waited >72 hours days between symptom onset and hospital presentation (P=0.03). CONCLUSION: Although treatment algorithms are an attractive tool to guide clinicians and resource allocation, they need to take into account the local population characteristics before routine implementation. LEVEL OF EVIDENCE: Level IV-retrospective cohort study.

Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis.

BACKGROUND: We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO). METHODS: Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1-17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14-42 days total). Primary endpoint: protocol-defined clinical improvement by Day 5 in the modified intention-to-treat (MITT) population (confirmed AHO, ≥1 dose of study treatment); differences between study arms were evaluated using a prespecified 15% noninferiority margin for daptomycin. RESULTS: Seventy-three patients per arm received treatment. Pathogens were isolated from 62% of patients (83% methicillin-susceptible Staphylococcus aureus, 9% methicillin-resistant S. aureus [MRSA]). Clinical improvement by Day 5 was observed in 55/71 (78%) daptomycin- and 58/70 (83%) comparator-treated MITT patients (95% confidence interval [CI]: -19.4, 7.4). This difference was not statistically significant; however, daptomycin did not meet the prespecified 15% noninferiority margin, since the lower bound of the 95% CI extended below 15%. Overall, 82% of daptomycin and 87% of comparator patients achieved clinical cure at the test-of-cure visit (secondary endpoint). More comparator patients had treatment-emergent (63% vs. 46%) and treatment-related (18% vs. 7%) adverse events. CONCLUSIONS: Differences between daptomycin and comparator for the primary endpoint were not statistically significant; however, prespecified noninferiority criteria for daptomycin were not met. With insufficient cases of confirmed MRSA, we could not evaluate daptomycin for MRSA AHO. Our nonvalidated protocol design yields valuable information for implementing future trials in AHO (ClinicalTrials.gov NCT01922011).

Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial.

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.

Detection of extremity chronic traumatic osteomyelitis by machine learning based on computed-tomography images: A retrospective study.

Despite the availability of a series of tests, detection of chronic traumatic osteomyelitis is still exhausting in clinical practice. We hypothesized that machine learning based on computed-tomography (CT) images would provide better diagnostic performance for extremity traumatic chronic osteomyelitis than the serological biomarker alone. A retrospective study was carried out to collect medical data from patients with extremity traumatic osteomyelitis according to the criteria of musculoskeletal infection society. In each patient, serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer were measured and CT scan of the extremity was conducted 7 days after admission preoperatively. A deep residual network (ResNet) machine learning model was established for recognition of bone lesion on the CT image. A total of 28,718 CT images from 163 adult patients were included. Then, we randomly extracted 80% of all CT images from each patient for training, 10% for validation, and 10% for testing. Our results showed that machine learning (83.4%) outperformed CRP (53.2%), ESR (68.8%), and D-dimer (68.1%) separately in accuracy. Meanwhile, machine learning (88.0%) demonstrated highest sensitivity when compared with CRP (50.6%), ESR (73.0%), and D-dimer (51.7%). Considering the specificity, machine learning (77.0%) is better than CRP (59.4%) and ESR (62.2%), but not D-dimer (83.8%). Our findings indicated that machine learning based on CT images is an effective and promising avenue for detection of chronic traumatic osteomyelitis in the extremity.

Change in Bone CT Attenuation and C-reactive Protein Are Predictors of Bone Biopsy Culture Positivity in Patients With Vertebral Discitis/Osteomyelitis.

STUDY DESIGN: Case-control study. OBJECTIVE: The objective of this study was to identify the best laboratory and imaging factors to predict bone biopsy culture positivity in the setting of vertebral discitis/osteomyelitis (VDO). SUMMARY OF BACKGROUND DATA: Good predictors of bone biopsy culture positivity in the setting of VDO are unknown. METHODS: Retrospective review was performed for 46 patients who underwent CT-guided bone biopsy for the evaluation of clinically confirmed VDO. Erythrocyte sedimentation rate, C-reactive protein (CRP), mean CT attenuation of the biopsied bone, and the change in the CT attenuation of the bone compared to unaffected vertebral bone (delta CT attenuation) were measured. Receiver-operator characteristic curve analyses were performed to identify the optimal threshold value for each variable. A multivariable logistic regression model was used to predict the probability of a positive bone culture using delta CT attenuation and CRPx100% fold above normal. RESULTS: For one of the 46 VDO patients, bone cultures were not obtained. Approximately 35.6% (16/45) of bone cultures were positive. The most significant predictors of bone culture positivity were CRP x100% fold above normal (P = 0.011) and delta CT attenuation (P = <0.001). Optimized predictive thresholds were calculated to be CRP 4-fold above normal reference value (90.9% sensitivity, 73.7% specificity), or if the CT attenuation of the affected vertebral body was >25.9 HU lower relative to unaffected bone (93.8% sensitivity, 75.0% specificity). CONCLUSION: Delta CT attenuation, as well as CRP level over four times the upper limits of normal, were the strongest predictors for bone culture positivity in patients with VDO. LEVEL OF EVIDENCE: 3.

Role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics.

OBJECTIVE: To analyse the predictive role of inflammatory markers in the healing time of diabetic foot osteomyelitis treated by surgery or antibiotics. METHODS: An observational study of patients with diabetic foot ulcers (DFU) and clinically suspected osteomyelitis. The patients underwent surgical or antibiotic treatment for bone infection in a specialised diabetic foot unit. Blood samples were taken from each patient to analyse biomarkers. The main outcome was the number of weeks until healing occurred. RESULTS: A total of 116 patients took part in the study. The number of weeks until healing was similar for both groups (surgical n=96 and antiobiotic n=20, treatments). No association was observed among biomarkers as predictors of time-to-healing. CONCLUSION: There is not enough evidence to define the prognostic role of inflammatory markers in the healing time of DFUs complicated with diabetic foot osteomyelitis, regardless of the treatment administered.

Atherogenic Index of Plasma: A Potential Biomarker for Clinical Diagnosis of Diabetic Foot Osteomyelitis.

Background: Osteomyelitis of the diabetic foot is a costly health problem worldwide. Early and accurate diagnosis of the disease in patients with diabetic foot infections is needed urgently and will have an important role in diabetic foot management. Methods: This was a case-control study of subjects with diabetic foot ulcers admitted to Beijing Shijitan Hospital from September 2015 to April 2018. We compared differences in the atherogenic index of plasma (AIP) in patients with or without osteomyelitis. Results: The mean AIP of 165 patients with osteomyelitis was 0.23 ± 0.24, which was significantly higher than the mean AIP of patients without osteomyelitis. Higher AIP values were associated with a considerably higher risk of osteomyelitis with an odds ratio of 1.81 (95% confidence interval [CI] 0.71-4.61), 4.70 (1.88-11.75), 5.03 (2.06-12.25) and 1.74 (1.33-2.28). Moreover, at a cut-off of 0.184, the AIP value showed a sensitivity of 84.3% and a specificity of 83.1% in the discriminatory identification of diabetic foot osteomyelitis. Conclusions: Elevated AIP was significantly associated with diabetic foot osteomyelitis, supporting the use of this index as a biomarker for the diagnosis in clinical practice.

First-4-week erythrocyte sedimentation rate variability predicts erythrocyte sedimentation rate trajectories and clinical course among patients with pyogenic vertebral osteomyelitis.

BACKGROUND: The trajectory pattern of erythrocyte sedimentation rate (ESR) in patients with pyogenic vertebral osteomyelitis (PVO) and its clinical significance is unclear. We further evaluated whether the first-4-week ESR variability can predict the trajectory pattern, treatment duration and recurrence of PVO. METHODS: The longitudinal ESR patterns of adults with PVO within the first 6 months were characterized through group-based trajectory modeling (GBTM). The ESR variability within the first 4 weeks was defined using the absolute difference (AD), coefficient of variation, percent change, and slope change. The first-4-week ESR variabilities were analyzed using ordinal logistic regression to predict the 6-month ESR trajectory and using logistic regression to predict treatment duration and recurrence likelihood. The discrimination and calibration of the prediction models were evaluated. RESULTS: Three ESR trajectory patterns were identified though GBTM among patients with PVO: Group 1, initial moderate high ESR with fast response; Group 2, initial high ESR with fast response; Group 3, initial high ESR with slow response. Group 3 patients (initial high ESR with slow response) were older, received longer antibiotic treatment, and had more comorbidities and higher recurrence rates than patients in the other two groups. The initial ESR value and ESR - AD could predict the 6-month ESR trajectory. By incorporating the first-4-week ESR variabilities and the clinical features of patients, our models exhibited moderate discrimination performance to predict prolonged treatment (≥12 weeks; C statistic, 0.75; 95% confidence interval [CI], 0.70 to 0.81) and recurrence (C statistic, 0.69; 95% CI, 0.61 to 0.78). CONCLUSIONS: The initial ESR value and first-4-week ESR variability are useful markers to predict the treatment duration and recurrence of PVO. Future studies should validate our findings in other populations.

The diagnostic value of soluble urokinase-type plasminogen activator receptor (suPAR) for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

BACKGROUND: There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. METHODS: Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. RESULTS: The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3-5 days post-OP, and 6-11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6-11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37-0.79), p < 0.0001. The values for the area under the receiver operating characteristics curve (AUC) for pre-OP and the overall model post-OP were 0.88 (95% CI: 0.76-1.00) and 0.84 (95% CI: 0.71-0.97) for suPAR, 0.93 (95% CI: 0.85-1.00) and 0.77 (95% CI: 0.62-0.93) for CRP, and 0.98 (95% CI: 0.96-1.00) and 0.91 (95% CI: 0.82-1.00) for the combination of suPAR and CRP. The AUC for suPAR pre-OP revealed an optimum cut-off value, sensitivity, specificity, NPV, and PPV of 2.96 ng/mL, 0.69, 1.00, 0.80, and 1.00, respectively. For CRP, these values were 11.58 mg/L, 0.88, 0.90, 0.90, and 0.88, respectively. CONCLUSION: The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019.

Inflammatory markers limitations in the diagnosis of pediatric calcaneal osteomyelitis.

Calcaneal osteomyelitis is an uncommon, but clinically important emergent condition in the differential of the limping child. Early recognition is paramount to prevent complications from delayed diagnosis like formation of periosteal abscesses or growth plate injury. The diagnosis of pediatric osteoarticular infection relies on a combination of clinical exam, imaging and inflammatory markers. Erythrocyte sedation rate (ESR) and C-reactive protein (CRP) have reported sensitivities for osteomyelitis of 94% and 95%, respectively. However, clinicians should be aware that certain clinical factors can decrease the reliability of inflammatory markers in this pediatric condition. Location of infection in small bones like the calcaneus can lead to significantly lower sensitivities than in long bones. Pretreatment with antibiotics prior presentation can also decrease the reliability of ESR and CRP. In this case, we highlight two unique clinical factors that diminish the sensitivity of commonly used inflammatory markers in the diagnosis of pediatric osteomyelitis.

Is Hypercalcemia a Frequent Complication following Local Use of Calcium Sulfate with Antibiotics for the Treatment of Extremity Posttraumatic Osteomyelitis? A Preliminary Study.

BACKGROUND: Previous study had reported hypercalcemia as a frequent complication (20%) following local use of antibiotic-eluting calcium sulfate (CS) during treatment of periprosthetic joint infections (PJIs). However, whether this complication may occur in patients who receive local CS implantation for management of posttraumatic osteomyelitis (OM) remains unclear. METHODS: Between April 2016 and May 2017, we included 55 patients with extremity posttraumatic OM who received local antibiotic-loaded CS therapy. Serum calcium levels were detected preoperatively and on the 1st, 3rd, and 7th postoperative days (PODs). Comparisons were performed regarding serum calcium levels among the four time points and between two different CS volume groups (≤ 20 cc group and > 20 cc group). Additionally, potential associations were examined regarding CS volume and preoperative calcium level with postoperative calcium levels, respectively. RESULTS: Altogether 46 males and 9 females were included, with a median CS volume of 20 cc. Outcomes showed that prevalence of asymptomatic hypocalcemia was more frequent, with 16.4% before surgery and 60%, 53.8%, and 25% on the 1st, 3rd, and 7th PODs, respectively. Hypercalcemia was not found in any patients, at any time point. In addition, significant differences were identified regarding serum calcium levels among different time points, suggesting significantly decreased calcium levels on the 1st (P < 0.001) and 3rd PODs (P < 0.001) and back to near preoperative level on the 7th POD (P = 0.334). However, no statistical differences were observed regarding serum calcium levels between the two CS volume groups at any time points (P > 0.05). Moreover, no significant links were identified between CS volume and postoperative calcium levels (P > 0.05). Serum calcium levels on the 3rd (P = 0.019) and 7th PODs (P = 0.036) were significantly associated with the preoperative calcium level. CONCLUSIONS: In contrast to what had occurred in PJI patients, asymptomatic hypocalcemia appeared to be more frequent in this cohort with posttraumatic OM. Hypercalcemia may be an infrequent complication before and after local CS use for the treatment of extremity posttraumatic OM.

Evaluation of Empirical Antibiotic Treatment in Culture Negative Pyogenic Vertebral Osteomyelitis.

AIM: To investigate the efficacy of empirical antibiotic treatment in culture-negative pyogenic vertebral osteomyelitis (PVO) cases. MATERIAL AND METHODS: The records of patients with culture-negative PVO who were treated at infectious diseases and neurosurgery outpatient clinics in the past four years were examined retrospectively. The control group comprised healthy subjects with similar age, gender, and body mass index but without pathology. The comparison of the groups was performed by analysis of variance. Statistical significance was accepted as p < 0.05. RESULTS: No statistically significant difference in the white blood cell count and erythrocyte sedimentation rate was found between the spondylodiscitis and the healthy subject groups when the blood parameters obtained before and after the treatment (p > 0.05). However, a statistical significance was assessed in the results of the comparison for C-reactive protein (p < 0.05). CONCLUSION: In the context of evidence-based medicine and the rational use of antibiotics, it is clear that antibiotics should be preferred according to the culture antibiogram results in the treatment of infectious diseases.