The Utility of Sulfur Colloid Imaging to Differentiate Charcot's Neuroarthropathy from Osteomyelitis: A Case Study.

Charcot's neuroarthropathy and osteomyelitis can have similar initial presentations. The ability to differentiate between the two pathologic conditions is essential, as each requires different treatment. We present a case of a 53-year-old woman with pain, swelling, and warmth in her left first metatarsophalangeal joint and first tarsometatarsal joint. Radiographs showed comminuted fractures at the base of the first metatarsal. Osteomyelitis was suspected by the primary team based on physical findings and a history of previous first metatarsophalangeal joint arthrodesis. A triphasic bone scan and an indium white blood cell scan were positive for osteomyelitis. The podiatric medical team was suspicious for possible Charcot's neuroarthropathy based on physical findings and uncontrolled blood glucose levels at the time of her previous arthrodesis. A sulfur colloid scan was performed and compared with an indium scan, which showed no evidence of osteomyelitis. This case demonstrates the usefulness of sulfur colloid imaging compared with an indium white blood cell scan to differentiate osteomyelitis from Charcot's neuroarthropathy. This case also highlights the importance of using clinical judgment to make the correct diagnosis.

Modified "SUPERhip2" to Reconstruct Postinfectious Femoral Neck Pseudoarthrosis (Hunka Type 3): A Case Report.

CASE: We report a case of a 3-year-old girl who developed a post-infectious femoral neck pseudoarthrosis after a proximal hematogenous femoral osteomyelitis (type 3 according to Hunka classification of the sequelae of the septic hip in children). The patient was treated by a modified "SUPERhip 2" procedure (a reconstructive procedure described to reconstruct congenital femoral neck pseudoarthrosis). This report describes the surgical technique in details and discusses the advantages, pitfalls, and complications and possible complications. CONCLUSION: Our modification simplifies the "SUPERhip 2" procedure. Postinfectious neck pseudoarthrosis was successfully treated, and we believe this modification is applicable for the treatment of congenital femoral neck pseudoarthrosis as well.

Type 2 diabetes mediates the causal relationship between obesity and osteomyelitis: A Mendelian randomization study.

Mendelian randomization (MR) analysis was used to determine the causal relationship between Type 2 diabetes (T2D) and osteomyelitis (OM). We performed MR analysis using pooled data from different large-scale genome-wide association studies (GWAS). Instrumental variables were selected based on genome-wide significance, instrumental strength was assessed using F-values, and thresholds for the number of exposed phenotypes were further adjusted by Bonferroni correction. univariable and multivariable MR analyses were performed to assess causal effects and proportions mediated by T2D. IVW (inverse variance weighting) showed a significant genetic effect of osteomyelitis on the following: After correction by Bonferroni, univariable analyses showed that childhood body mass index (BMI) was not significantly associated with genetic susceptibility to OM [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.02, 1.55; P = .030], not significantly associated with adulthood BMI (OR, 1.28; 95% CI, 1.02, 1.61; P = .034), significantly associated with waist circumference (OR, 1.84; 95% CI, 1.51, 2.24; P < .001), and significantly associated with hip circumference (OR, 1.52; 95% CI, 1.31, 1.76; P < .001). Meanwhile, multivariable analyses showed no significant effect of childhood BMI on OM (OR, 1.16; 95% CI, 0.84, 1.62; P = .370), no significant effect of adulthood BMI on OM (OR, 0.42; 95% CI, 0.21, 0.84; P = .015), a significant association between waist circumference and OM (OR, 4.30; 95% CI, 1.89, 9.82; P = .001), T2D mediated 10% (95% CI, 0.02, 0.14), and no significant association between hip circumference and OM (OR, 1.01; 95% CI, 0.54, 1.90; P = .968). Our study provides evidence for a genetically predicted causal relationship among obesity, T2D, and OM. We demonstrate that increased waist circumference is positively associated with an increased risk of OM and that T2D mediates this relationship. Clinicians should be more cautious in the perioperative management of osteomyelitis surgery in obese patients with T2D. In addition, waist circumference may be a more important criterion to emphasize and strictly control than other measures of obesity.

Trifocal versus Pentafocal bone transport in segmental tibial defects: a matched comparative analysis for posttraumatic osteomyelitis treatment.

PURPOSE: The objective of this study was to evaluate and compare the effectiveness and clinical results of trifocal bone transport (TBT) and pentafocal bone transport (PBT) in treating distal tibial defects > 6 cm resulting from posttraumatic osteomyelitis, highlighting the potential advantages and challenges of each method. METHODS: A retrospective assessment was conducted on an overall population of 46 eligible patients with distal tibial defects > 6 cm who received treatment between January 2015 and January 2019. Propensity score analysis was used to pair 10 patients who received TBT with 10 patients who received PBT. The outcomes assessed included demographic information, external fixation time (EFT), external fixation index (EFI), bone and functional outcomes assessed using the Association for the Study and Application of the Method of Ilizarov (ASAMI) scoring system, and postoperative complications evaluated using the Paley classification. RESULTS: The demographic and baseline data of the two groups were comparable. Following radical debridement, the average tibial defect was 7.02 ± 0.68 cm. The mean EFT was significantly shorter in the PBT group (130.9 ± 16.0 days) compared to the TBT group (297.3 ± 14.3 days). Similarly, the EFI was lower in the PBT group (20.67 ± 2.75 days/cm) than in the TBT group (35.86 ± 3.69 days/cm). Both groups exhibited satisfactory postoperative bone and functional results. Pin site infection was the most common complication and the rates were significantly different between the groups, with the PBT group demonstrating a higher incidence. CONCLUSION: Both TBT and PBT effectively treat posttraumatic tibial defects greater than 6 cm, with PBT offering more efficient bone regeneration. However, PBT is associated with a higher rate of pin site infections, highlighting the importance of careful management in these complex procedures and emphasizing the need for expert surgical execution and tailored treatment approaches in orthopedic reconstructive surgery.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Predictors of operative management in diabetic foot ulcers.

BACKGROUND & AIMS: Surgery plays a key role in the management of complicated diabetic foot disease (DFD). Currently, indications for medical versus surgical management are poorly defined. Prompt identification of patients who require surgery may reduce morbidities and length of hospital stay. This study aims to analyse factors in DFD that necessitate early surgical interventions. METHODS: All patients admitted under a multi-disciplinary diabetic foot team in a tertiary institution over 2 years were included in a retrospective case-control study comparing patients who received medical management and patients who received surgical management. Logistic regression was performed to identify factors associated with surgical management of diabetic foot complications. RESULTS: Three hundred and forty patients were included. 49% of patients required surgical management. Toe ulceration, elevated C-reactive protein (CRP), and the presence of osteomyelitis were associated with surgical management. Multivariate analysis calculated an odds ratio (OR) of 1.01 for CRP (p < 0.001), OR 2.19 (p < 0.019) favouring surgical management for forefoot ulcers, and OR 2.2 (p < 0.019) if osteomyelitis was present. CONCLUSIONS: Patients with elevated CRP levels, a forefoot diabetic ulcer and established osteomyelitis were more likely to undergo surgical management. Prompt recognition of these patients has the potential benefit of earlier decision making in definitive surgical interventions.

[Transcriptomic characteristics analysis of bone from chronic osteomyelitis].

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion.

Introduction: Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking. Methods: Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls. Results: Our study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells. Discussion: We conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

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.

Aberrant Expression of SLC7A11 Impairs the Antimicrobial Activities of Macrophages in Staphylococcus Aureus Osteomyelitis in Mice.

Staphylococcus aureus (S. aureus) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b+F4/80+ macrophages, and validated a predominant distribution of SLC7A11 in F4/80+ cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo. Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis.

Cat-scratch disease: a rare cause of osteomyelitis.

Cat-scratch disease is a zoonosis caused by Bartonella henselae, characterised by regional lymphadenopathy. Rarer presentations, such as osteomyelitis, can occur.We present an adolescent girl with severe right lumbar pain and fever, without animal contacts or recent travels. On examination, pain on flexion of torso, movement limitation and marked lordosis were noted, but there were no inflammatory signs, palpable masses or lymph nodes. Serological investigations revealed elevated inflammatory markers. Imaging revealed a paravertebral abscess with bone erosion. Several microbiological agents were ruled out. After a second CT-guided biopsy, PCR for Bartonella spp was positive. At this point, the family recalled having a young cat some time before. Cat-scratch disease was diagnosed, and complete recovery achieved after treatment with doxycycline and rifampicin.Cat-scratch disease is a challenging diagnosis in the absence of typical features. However, B. henselae must be investigated if common pathogens are ruled out and response to therapy is poor.

Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis.

PURPOSE: To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO). MATERIALS AND METHODS: Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury. RESULTS: Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group. CONCLUSIONS: Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

Neonatal Osteomyelitis.

Osteomyelitis is a serious and potentially life-threatening condition affecting the skeletal system of newborns. The condition is relatively rare in neonates but occurs at higher rates in high-risk pregnancies, in preterm infants, and with the use of invasive devices. As a result of the anatomy and immature immune system of newborns, neonates differ in presentation, diagnosis, and management of osteomyelitis compared to patients of other age groups. An understanding of these differences will assist clinicians in the prompt diagnosis and management of this neonatal infection and lead to improved long-term outcomes.

Radiological manifestations and clinical findings of patients with oncologic and osteoporotic medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p < 0.01) and had a longer duration of medication usage than the oncologic group (58.1 vs. 28.0 months, p < 0.01). Pus discharge and swelling were more common in the osteoporotic group (p < 0.05), whereas bone exposure was more frequent in the oncologic group (p < 0.01). The mandibular cortical index (MCI) in panoramic radiographs was higher in the osteoporotic group (p < 0.01). The mean sequestra size was larger in the oncologic group than in the osteoporotic group (15.3 vs. 10.6 mm, p < 0.05). The cured rate was significantly higher in the osteoporotic group (66.3% vs. 33.3%, p < 0.01). Oncologic MRONJ exhibited distinct clinical findings including rapid disease onset, fewer purulent signs, and lower cure rates than osteoporotic MRONJ. Radiological features such as sequestrum size on CT scan, and MCI values on panoramic radiographs, may aid in differentiating MRONJ in osteoporotic and oncologic patients.

Lethal mycotic pseudoaneurysm presenting as isolated sixth nerve palsy.

Pseudoaneurysm of the internal carotid artery caused by skull base osteomyelitis (SBO) is a lethal condition seen in immunocompromised patients, predominantly those with diabetes mellitus. Cranial nerve involvement is a common complication and generally indicates a poor prognosis. We report the case of a 62-year-old diabetic patient who presented with isolated sixth cranial nerve palsy. She had uncontrolled blood sugar levels and high erythrocyte sedimentation rate, and she suffered from pyelonephritis. Neuroimaging detected SBO with multiple secondary mycotic pseudoaneurysms prominent at the petrocavernous junction. Ischemia is the most common etiology for an isolated abducens nerve palsy, but in certain cases neuroimaging is warranted to prevent life-threatening complications. This case highlights the importance and urgency of identifying and managing such conditions.

Disseminated Cryptococcus neoformans infection involving multiple bones and lung in an immunocompetent patient: a case report.

BACKGROUND: Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent. CASE PRESENTATION: An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition. CONCLUSIONS: This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.

Dilemma with implant placement in patients with florid cemento-osseous dysplasia: A literature review.

METHODOLOGY: An electronic search was done in PUBMED, SCOPUS, and a hand search was done in radiology, periodontology, and oral surgery journals. The search yielded 428 results, from which only 6 articles were selected for this literature review. Both prospective and retrospective studies were included. Clinical studies with information on the pre-implant condition of the site, detailed implant procedure, and follow-up after implant placement of more than 6 months were only considered for this review. RESULTS AND CONCLUSION: Limited clinical studies, shorter follow-up periods were the shortcomings of this review. However, it can be summarized that dental implants should not be placed at the site of FCOD, however can be placed at adjacent sites. Variations in implant type or the implant length had no bearing on the survival of implants at the sites of FCOD.

Clinical outcomes of perforator-based propeller flaps versus free flaps in soft tissue reconstruction for lower leg and foot trauma: a retrospective single-centre comparative study.

BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.