Osteomyelitis Group Research Articles

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Logistic regression analysis of multiple rapid admission hematological indicators to determine the risk of osteomyelitis in infected children.

To analyze the differences of multiple rapid admission hematological indicators between children with acute osteomyelitis (AO) and children with other orthopedic infectious diseases and clarify the characteristics of admission inspection hematological indicators of children with AO. Retrospective analysis of this pilot study was proceeded on 144 children with limbs infectious diseases, who were treated in our hospital. According to their final diagnosis, they were divided into osteomyelitis group (n = 57) and non-osteomyelitis group (n = 87). Case data were collected, including sex, age, body temperature, white blood cell (WBC), C-reactive protein (CRP), etc. The differences in these indexes between the two groups of patients were compared, and then, the index with significant differences was selected for univariate and multivariate logistic regression analysis. There were significant differences between the two groups in age, body temperature, CRP, ESR, fibrinogen, total bilirubin, alanine aminotransferase, aspartate aminotransferase (AST), glutamyl transpeptidase, creatinine, PCT, albumin (ALB), and ALB globulin ratio (A/G) ( P < 0.05). The results of univariate and multivariate logistic regression analysis showed that the age of ≥5 years (4.592, 1.711-12.324), WBC (>1.5 × 10 9 /L) (0.271, 0.102-0.718), ESR (>50 mm/h) (6.410, 2.291-17.936), PCT (>0.06 µg/L) (3.139, 1.066-9.243), and AST (>40 U/L) (11.174, 1.718-72.666) was an independent risk factor of AO in children with orthopedic infectious diseases ( P < 0.05). For newly admitted children with orthopedic infectious diseases, if the age ≥ 5 years, WBC ≤ 1.5 × 10 9 /L, ESR > 50 mm/h, PCT > 0.06 µg/L, and AST > 40 U/L, the occurrence of AO should be alerted.

Study of Diabetic Foot Problems Among Patients Attending the Diabetic Foot Clinic at Royal Hampshire County Hospital, United Kingdom: A Single-Centre Experience.

Background Patients with diabetes mellitus (DM) are on the rise all over the world. Simultaneously, the complications of DM are also increasing. Diabetes-related foot problems have been another concern among health professionals, especially foot ulcers, osteomyelitis, and amputations. Objectives We determined the prevalence of gender, age, types of DM including non-diabetics, various foot-related presentations, complications, and their outcomes. Methods A retrospective descriptive cross-sectional study was conducted among new patients attending a diabetic foot clinic over a period of six months, from January 1, 2019 to June 30, 2019. To confirm the outcome of the study, all of them were followed up for at least four months from the date of diagnosis. Results The study showed that most patients were males (65.5%). The most common age group for diabetic foot problems was 81-90 years, and about 80% of the foot problems were diagnosed in patients over 60 years. The study disclosed that 86.2% of the population had type 2 DM, 56.9% had ulcers, and 13.8% had osteomyelitis. The outcome of our study demonstrated that 65.5% of the patients were cured and discharged within four months of the diagnosis, but 10.3% of the population needed amputation. During the four-month follow-up period, 3.4% of our study population died due to non-foot-related causes. A total of 48.1% of our ulcer patients were discharged within eight weeks of diagnosis. However, 26% of ulcer patients and 75% of osteomyelitis patients needed more than four months to be discharged. Peripheral neuropathy and peripheral arterial disease (PAD) were present in 91% of ulcer patients. Among our osteomyelitis group, 100% had peripheral neuropathy, and 87.5% had PAD. About 20% of ulcer patients and none of the osteomyelitis patients were diagnosed with chronic kidney disease (CKD) stages beyond 3b. About 2/3rd of our ulcer and osteomyelitis population had an HbA1C level of more than 7.5%. Conclusion Male patients over 60 years of age with type 2 DM are more at risk of developing diabetes-related foot issues. Ulcer with or without osteomyelitis was the most common complication among our study population. Results showed that a significant amount of osteomyelitis patients underwent foot amputation. Poor glycaemic control of HbA1C of more than 7.5%, peripheral neuropathy, and PAD were the most common risk factors for developing foot-related complications. Prolonged use of antibiotics and a dedicated professional team may be needed to manage these complications successfully.

Preliminary evaluation of dual-energy CT to quantitatively assess bone marrow edema in patients with diabetic foot ulcers and suspected osteomyelitis

ObjectivesThe purpose of this study is to evaluate the value of dual-energy CT (DECT) with virtual non-calcium (VNCa) in quantitatively assessing the presence of bone marrow edema (BME) in patients with diabetic foot ulcers and suspected osteomyelitis.MethodsPatients with a diabetic foot ulcer and suspected osteomyelitis that underwent DECT (80 kVp/Sn150 kVp) with VNCa were retrospectively included. Two observers independently measured CT values of the bone adjacent to the ulcer and a reference bone not related to the ulcer. The patients were divided into two clinical groups, osteomyelitis or no-osteomyelitis, based on the final diagnosis by the treating physicians.ResultsA total of 56 foot ulcers were identified of which 23 were included in the osteomyelitis group. The mean CT value at the ulcer location was significantly higher in the osteomyelitis group (− 17.23 ± 34.96 HU) compared to the no-osteomyelitis group (− 69.34 ± 49.40 HU; p < 0.001). Within the osteomyelitis group, the difference between affected bone and reference bone was statistically significant (p < 0.001), which was not the case in the group without osteomyelitis (p = 0.052). The observer agreement was good for affected bone measurements (ICC = 0.858) and moderate for reference bone measurements (ICC = 0.675). With a cut-off value of − 40.1 HU, sensitivity was 87.0%, specificity was 72.7%, PPV was 69.0%, and NPV was 88.9%.ConclusionDECT with VNCa has a potential value for quantitatively assessing the presence of BME in patients with diabetic foot ulcers and suspected osteomyelitis.Key Points• Dual-energy CT (DECT) with virtual non-calcium (VNCa) is promising for detecting bone marrow edema in the case of diabetic foot ulcers with suspected osteomyelitis.• DECT with VNCa has the potential to become a more practical alternative to MRI in assessing the presence of bone marrow edema in suspected osteomyelitis when radiographs are not sufficient to form a diagnosis.

Bacillus Calmette-Guérin (BCG) osteomyelitis among children: Experience in a single tertiary center in central Taiwan

The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

Изменение антиоксидантно/прооксидантного равновесия у пациентов с приобретенными укорочениями костей голени на этапах удлинения по Илизарову

Introduction Optimization of the conditions of distraction osteogenesis using the method of G.A. Ilizarov remains an important challenge to ensure a reduction in the number of complications and an increase in the effectiveness of this technology. The aim of the study was to study the changes in the antioxidant/prooxidant balance in patients with acquired shortening of the lower leg bones at the stages of the Ilizarov lengthening procedure. Methods The antioxidant/prooxidant status was studied in 12 patients with shortening of one of the lower legs resulting from hematogenous osteomyelitis (group 1) and in 13 patients with post-traumatic shortening of one of the lower legs (group 2). The level of peroxidation products, the activity of superoxide dismutase and vitamins E and A in the blood of these patients were assessed in the dynamics of monofocal bone lengthening using the Ilizarov method. Results It was found that in patients with acquired shortening of the shin bones, regardless of the shortening etiology, during surgical lengthening, an increase in the level of peroxidation products in the blood was observed with a decrease in the level of vitamin E and an increase in superoxide dismutase activity. Discussion The data obtained, together with the current findings from fundamental research, allow us to note that the use of antioxidants (AOs) in patients undergoing segment length correction using the Ilizarov technology is possible from two positions. 1. The positive effect of AOs in terms of stimulation of distraction osteogenesis has been proven. 2. AOs have a systemic effect in the regulation of the recovery processes in the paraosseous tissues of the limb segment under lengthening. Conclusion Peroxidation is activated in the course of surgical lengthening of the lower leg bones in patients with acquired shortenings, regardless of the shortening etiology. The use of antioxidants in such patients can specifically inhibit peroxidation, thereby reducing the risk of provoking bone formation disorders.

Incidence and risk factors for sternal osteomyelitis after median sternotomy.

BackgroundSternal osteomyelitis (OM) after median sternotomy is the rarest form of deep sternal wound infections (DSWIs). A retrospective study was implemented to evaluate the incidence and potential risk factors of sternal OM after median sternotomy.MethodsWe analyzed 3,410 consecutive patients who underwent cardiothoracic surgery via median sternotomy from January 2005 to December 2019 at our institution. A sternal OM and control group without any sign of wound infections after median sternotomy were selected. Comparisons of the variables between the two groups were performed using the Student’s t-test and Fisher’s exact tests. The association of potential risk factors with sternal OM was tested by logistic regression analysis.ResultsA total of 16 patients (0.47%) had sternal OM after median sternotomy. None of the variables were different between the sternal OM patients and the control group including body mass index (BMI), diabetes mellitus (DM), hypertension (HTN), left ventricle (LV) function, transfusion, operation time, cardiopulmonary bypass (CPB) time and intensive care unit and ventilator days. By univariate analysis, none of the variables were associated with an increased risk of sternal OM.ConclusionsThe incidence of sternal OM after median sternotomy in our institution was 0.47% and there was no correlation between the known risk factors of DSWI and sternal OM in our study.

Diffusion-Weighted Imaging Distinguishes Between Osteomyelitis, Bone Marrow Edema, and Healthy Bone on Forefoot Magnetic Resonance Imaging.

Diagnosis of osteomyelitis by imaging can be challenging. The feasibility of diffusion-weighted imaging (DWI) as ancillary sequence was evaluated in this study. To evaluate DWI for differentiation between osteomyelitis, bone marrow edema, and healthy bone on forefoot magnetic resonance imaging (MRI). Prospective. A total of 60 consecutive patients undergoing forefoot MRI divided into three study groups (20 subjects each): osteomyelitis, bone marrow edema, and healthy bone. A 1.5T and 3T MRI scanners; readout-segmented multishot echo planar DWI. Two independent radiologists measured apparent diffusion coefficient (ADC) values within abnormal or healthy bone. ADC values were compared between groups (pairwise t-test with Bonferroni-Holm correction for multiple testing). Intraclass correlation coefficient (ICC) was calculated to assess inter-reader agreement. Threshold ADC values were determined as the cutoffs that maximized the sum of sensitivity and specificity. Receiver operating characteristic (ROC) analysis was performed with statistical threshold of P < 0.05. Inter-reader agreement was 0.92 in the healthy bone group and 0.78 in both the edema and osteomyelitis groups. Average ADC values were significantly different between groups: 1432 ± 222× 10-6 mm2 /sec (osteomyelitis), 1071 ± 196× 10-6 mm2 /sec (bone marrow edema), and 277 ± 89× 10-6 mm2 /sec (healthy bone). A threshold ADC value of 534× 10-6 mm2 /sec distinguishes between healthy and abnormal bone with specificity and sensitivity of 100% each. For distinction between osteomyelitis and bone marrow edema, two cutoff values were determined: a 95%-specificity cutoff indicating osteomyelitis (>1320× 10-6 mm2 /sec) and a 95%-sensitivity cutoff indicating bone marrow edema (<1155× 10-6 mm2 /sec). Diagnostic accuracy of 95% was achieved for 73% (29/40) of the subjects. DWI with ADC maps distinguishes between healthy and abnormal bone on forefoot MRI. Calculated cutoff values allow confirmation or exclusion of osteomyelitis in a high proportion of subjects. 2 TECHNICAL EFFICACY: Stage 2.

Bcl-2 and p53 as novel biomarkers for predicting malignant transformation in chronic osteomyelitis.

To find whether B-cell lymphoma 2 (bcl-2) and p53 proteins could be used as parameters to detect malignant transformation of chronic osteomyelitis. We also attempted to determine whether they could be used to differentiate between secondary squamous cell carcinoma (SCC) resulting from chronic osteomyelitis, and primary cutaneous squamous cell carcinoma. Retrospective study was conducted during 5years period, resulting in 7 patients in each group: secondary squamous cell carcinoma arising from chronic osteomyelitis, primary cutaneous squamous cell carcinoma, and chronic osteomyelitis patients. Immunohistochemistry staining with bcl-2 and p53 was performed with the pathologist blinded to the sample groups. Contingency coefficient test was performed to assess the correlation between the biomarker status (bcl-2 and p53) and the case groups. Significant moderate correlations of bcl-2 and p53 were found between groups of chronic osteomyelitis and squamous cell carcinoma arising from chronic osteomyelitis in terms of malignant transformation (p = 0.005 for bcl-2 and p = 0.031 for p53). Insignificant correlations of bcl-2 and p53 expression were found between primary cutaneous squamous cell carcinoma and secondary squamous cell carcinoma arising from chronic osteomyelitis group (p = 0.577). The expression of bcl-2 and p-53 is significantly correlated with chronic osteomyelitis malignant transformation into squamous cell carcinoma.

ICD-10 Diagnostic Coding for Identifying Hospitalizations Related to a Diabetic Foot Ulcer.

To estimate the positive predictive value (PPV) of Canadian ICD-10 diagnostic coding for the identification of hospitalization related to a diabetic foot ulcer (DFU). Hospitalizations related to a neuropathic and/or ischemic DFU were identified from the Discharge Abstract Database (DAD) records of a single Canadian tertiary care hospital between April 1, 2002 and March 31, 2019. The first coding approach required a most responsible diagnosis (MRDx) code for diabetes-specific foot ulceration or gangrene (DSFUG group). Three alternative coding approaches were also considered: MRDx code for lower-limb osteomyelitis (osteomyelitis group); lower-limb ulceration (LLU group); or lower-limb atherosclerotic gangrene (atherosclerosis group)-each in conjunction with a non-MRDx DSFUG code on the same DAD record. From all eligible DAD records, random samples were drawn for each coding group. DAD records were independently compared by a masked reviewer who manually abstracted data from the entire hospital record (reference standard). The PPV and 95% CI were generated. Out of 1,460 hospitalizations, a total of 300, 50, 33 and seven records were included from the DSFUG, osteomyelitis, LLU and atherosclerosis samples, respectively. Compared to the reference standard, the PPV for all 390 records was 88.5% (95% CI 84.9 to 91.5). The DSFUG group had the highest PPV (90.0%, 95% CI 86.0 to 93.2), followed by the atherosclerosis (85.7%, 95% CI 42.1 to 99.6), LLU (84.9%, 95% CI 68.1 to 94.9) and osteomyelitis (82.0%, 95% CI 68.6 to 91.4) groups. Based on data from a Canadian tertiary care hospital, the specified coding algorithms can be used to identify and study the management and outcomes of people hospitalized with a DFU in Ontario.

Magnetic resonance imaging texture analysis in the quantitative evaluation of acute osteomyelitis of the mandibular bone.

Accurate assessment of radiological images can help in early diagnosis and therapy of suppurative osteomyelitis (OM). The purpose of this study was to apply texture analysis to MRI as a means of quantitatively evaluating acute OM of the mandible. We analyzed the data from 38 patients who complained of pain and underwent MRI between April 2017 and March 2019. From the MRIs of these patients, with (n = 19) and without OM (n = 19), 279 radiomics features were extracted using short tau inversion recovery, data of the regions of interest and analyzed with MaZda v. 3.3. 10 features, including one histogram feature (90th percentile), eight gray-level co-occurrence matrix features (Sum Averg), and one gray-level run-length matrix feature (Horzl_RLNonUni), were selected using Fisher coefficient and compared between the acute OM and non-OM groups. The two groups were compared using Mann-Whitney U test with p value set at 0.05. All 10 radiomics features showed significant differences between the acute OM and non-OM groups (p < 0.05). MRI texture analysis has potential application in radiomics diagnosis of acute OM of the mandible.

Epidemiology and Management of Acute Hematogenous Osteomyelitis, Neonatal Osteomyelitis and Spondylodiscitis in a Third Level Paediatric Center.

Acute hematogenous osteomyelitis (AHOM) is a rare pathology in pediatric population. The aim of this study is to analyse the epidemiological data and the management, compared to European Society for Paediatric Infectious Disease (ESPID, European Society for Pediatric Infectious Diseases) guidelines 2017 of 216 children with AHOM, divided in three cohorts (neonatal-onset osteomyelitis, those with vertebral involvement and other types of osteomyelitis). We conducted a retrospective single center study, evaluating data from all the children (aged 0–18 years) consecutively admitted to the Meyer Children’s Hospital, during a period of ten years (1 January 2010–31 December 2019). Isolation of pathogen was possible in 65 patients and S. aureus was the most frequently involved (43/65 children). Magnetic Resonance Imaging (MRI, magnetic resonance imaging) was performed in 201/216 cases and was compatible with osteomyelitis in 185/201 of these children (92.03%). In the neonatal-onset osteomyelitis group the percentage of diagnostic ultrasound for osteomyelitis was 36.36% significantly higher than the other groups. The median duration of total antibiotic therapy was 37.5 days. In total, 186/199 children recovered without complications. The present study delineates three heterogeneous cohorts of patients. S. aureus is confirmed as the first pathogen for isolation in all three groups analysed. MRI represent a gold standard for diagnosis. Longer duration of antibiotics treatment was performed in neonatal and spondylodiscitis group, compared to the other types of osteomyelitis.

Efficacy of diffusion-weighted magnetic resonance imaging in the diagnosis of osteomyelitis of the mandible

This retrospective cohort study aimed to determine the diagnostic utility of apparent diffusion coefficient (ADC) values in the quantitative evaluation of mandibular osteomyelitis. We analyzed the records of 70 patients aged 30 to 90 years, with and without osteomyelitis, who underwent magnetic resonance imaging at the Nihon University School of Dentistry between April 2017 and March 2019. The mean ADC of bone marrow of patients without osteomyelitis and those with acute and chronic osteomyelitis of the mandible were calculated. Differences in ADC overall and in pair-wise comparisons were analyzed. Correlations with patient age were also calculated. The mean ADC values in the nonosteomyelitis, acute osteomyelitis, and chronic osteomyelitis groups were 0.87 ± 0.15×10-3, 1.24 ± 0.11×10-3, and 1.07 ± 0.13×10-3 mm2/s, respectively (P < .001 for all pair-wise comparisons). Receiver operating characteristic curve analysis revealed an ADC cut-off of 0.98 for osteomyelitis. Diagnostic values for predicting osteomyelitis were ≥ .81. No correlations of osteomyelitis with age were found. The ADC was significantly higher in the osteomyelitis groups than in the nonosteomyelitis group. This suggests that ADC may be a useful parameter for quantitative evaluation of mandibular osteomyelitis.

The diagnostic utility of size and apparent diffusion coefficient values for cervical lymph nodes in patients with osteomyelitis of the jaw bone.

The purpose of this study was to (1) clarify the size and apparent diffusion coefficient (ADC) value of lymph nodes (LN) in each state in their quantitative evaluation diffusion-weighted imaging, and (2) to determine the diagnostic utility of size and ADC values in the quantitative evaluation of LNs using diffusion-weighted imaging. This was a retrospective cohort study at our hospital conducted between April 2017 and March 2019. A total of 50 patients (20 men, 30 women) with 118 LNs, aged 34-90years (mean age 61.18years), undergoing magnetic resonance imaging examination were included in the study. The predictor variable was disease status. The primary outcome variable was the mean size and ADC values of the LNs. The other variables were age and sex. Data were analyzed using a Kruskal-Wallis test, and hoc Mann-Whitney tests with Bonferroni adjustment and a receiver operating characteristic (ROC) curve. P < 0.05 was considered to indicate statistical significance. We analyzed the records of 50 patients (118 LNs) with and without osteomyelitis. Of these, 21 had acute osteomyelitis, and 16 had chronic osteomyelitis. The size and ADC values of LNs in the osteomyelitis group were significantly greater and higher, respectively, than those in the non-myelitis group (P < 0.01). ROC analysis revealed a cutoff short-axis size of 4.42 and 4.04mm for lymphadenopathy caused by osteomyelitis, corresponding to levels IB and level II, respectively. Moreover, the ADC cutoff values for the same were 0.85 and 0.86, respectively. The results suggest that size and ADC values are useful parameters for the quantitative evaluation of lymphadenopathy caused by osteomyelitis.

Development of hydrofluoric acid-cleaned silicon nitride implants for periprosthetic infection eradication and bone regeneration enhancement

Orthopedic implant is commonly associated with occurrence or relapse of osteomyelitis. This study developed a hydrofluoric acid (HF) cleaned silicon nitride (Si3N4) implant Si3N4_AC for osteomyelitis control and established a rat tibial osteomyelitis model to evaluate its efficacy on eradicating periprosthetic infection and enhancing bone regeneration. In vitro studies revealed Si3N4_AC had improved biocompatibility and inhibited Staphylococcus aureus adhesion. A custom-made Si3N4_AC implant was prepared and inserted into the rat tibia longitudinal cavity inoculated with Staphylococcus aureus. The in vivo bacteriostatic and osteogenic efficacies of Si3N4_AC implant were evaluated by histological, microbiological and Micro-CT analyses and compared with implants of pure Ti and Si3N4 . Si3N4_AC implant group revealed 99.5% inhibition of periprosthetic Staphylococcus aureus compared to the osteomyelitis group after 14 days post-operation. Implant-adhering bacteria density of Si3N4_AC was also much lower than pure Ti and Si3N4. In addition, micro-CT evaluation of peri-implant bone formation under the condition of periprosthetic osteomyelitis after 30 days post-surgery confirmed the osteogenic ability of Si3N4_AC. Taken together, Si3N4_AC can be an effective orthopedic biomaterial to eradicate periprosthetic infection and enhance bone regeneration.

Persistent bone resorption lacunae on necrotic bone distinguish bisphosphonate-related osteonecrosis of jaw from denosumab-related osteonecrosis

Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.

How long can secondary resurfacing surgery be delayed with continuous irrigation therapy for gustilo-anderson type iii fracture? A retrospective clinical study

Background: The resurfacing of Gustilo–Anderson (GA) IIIB and C fractures remains challenging. Immediate debridement and external stabilization of the fracture followed by early internal fixation along with wound closure using flaps are recommended. Although it requires early soft tissue reconstruction, it is not always possible. We considered that continuous wound irrigation might reduce the chance of infection and extend the delay period until the secondary surgery. Patients and Methods: A total of 19 patients with GA IIIB and C fractures who underwent debridement and external fixation were evaluated. Among them, 18 cases were examined, excluding one who received amputation. Ten underwent wound-resurfacing surgery within 10 days after injury, and the other 8 did so after 11 days. We examined the frequency of osteomyelitis development depending on the timing of wound closure and predicted how long secondary wound closure surgery could be delayed on the application of continuous irrigation therapy. Results: Eight patients developed osteomyelitis. The number of days until wound closure in the group that developed osteomyelitis was significantly greater than in those who did not develop osteomyelitis group (P < 0.05). Only one patient (10%) developed osteomyelitis in the early resurfacing group, while 7 (87%) did so in the late resurfacing group. There was a significant difference between the groups (P < 0.01). Conclusion: This study showed that that the continuous irrigation method could extend the delay time until the secondary surgery for GA III fractures. However, it suggested that the waiting should be limited to a maximum of 10 days.

Clinical features of tuberculosis and Bacillus Calmette-Guérin (BCG) -associated adverse effects in children: A 12-year study

To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p=0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p=0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p=0.009), and had more systemic symptoms (67% vs 25%; p=0.007), lower absolute lymphocyte count (1230 vs 1850/μL; p=0.033), higher CRP level (5.62 vs 2.21mg/dL; p=0.024) and longer hospital stay (20 vs 11 days; p=0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0-20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

Investigation of biofilm production and its association with genetic and phenotypic characteristics of OM (osteomyelitis) and non-OM orthopedic Staphylococcus aureus

BackgroundStaphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains.MethodsA total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients’ inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates.ResultsBiofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses.ConclusionSome genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance.

Predicting osteomyelitis in patients whose initial MRI demonstrated bone marrow edema without corresponding T1 signal marrow replacement.

We endeavored to determine which characteristics of diabetic ulcers portend the strongest risk for osteomyelitis in patients whose initial T1-weighted imaging was normal. By determining which features have a greater risk for osteomyelitis, clinicians can treat patients more aggressively to reduce the sequela of inadequately treated osteomyelitis. We performed a retrospective analysis of MR imaging from 60 pedal ulcers with suspected osteomyelitis. Ulcer dimensions and depth were measured. Ratios of marrow ROI/joint fluid ROI on T2/STIR sequences were obtained. Progression to osteomyelitis on subsequent MRI was characterized by loss of normal marrow signal on T1-weighted images. Statistical analysis was performed with a two-sample t test and Cox proportional hazard model. A p value < 0.05 was used as the threshold for statistical significance. Sixty MR exams were identified. Thirty-four progressed to osteomyelitis. Marrow ROI/joint fluid ratios averaged 65% in the osteomyelitis group, and 45% in the non-osteomyelitis group, p < 0.001. ROI ratios > 53% had a 6.5-fold increased risk of osteomyelitis, p < 0.001. Proximity to bone averaged 6mm in the osteomyelitis group and 9mm in the non-osteomyelitis group, p = 0.02. Ulcer size averaged 4cm2 in the osteomyelitis group versus 2.4cm2 in the non-osteomyelitis group, p = 0.07. Ulcers greater than 3cm2 has a 2-fold increase in the risk of osteomyelitis, p = 0.04. Increasing bone marrow ROI signal/joint fluid ratios on T2/STIR images were the strongest risk factors for developing osteomyelitis, while ulcer size and depth are weaker predictors.