Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Cervical cancer most commonly spreads hematogenously to the lungs, liver, and bone. However, it rarely metastasizes to the foot. There is only one other case of cervical cancer with metastasis to the foot. In addition, the initial imaging of metastatic disease has difficulty in differentiating from infectious or other inflammatory processes, particularly in a clinical setting highly suspicious of infectious sources. Here, we present a rare case of cervical cancer metastasizing to the calcaneus masquerading as osteomyelitis, highlighting the importance of diagnostic imaging in conjunction with histological confirmation.

The treatment, maintenance, and suppression of infection in chronic wounds remain a challenge to all practitioners. From an infectious disease standpoint, knowing when a chronic wound has progressed from colonized to infected, when to use systemic antimicrobial therapy and when and how to culture such wounds can be daunting. With few standardized clinical guidelines for infections in chronic wounds, caring for them is an art form. However, there have been notable advances in the diagnosis, treatment, and management of infected wounds. This article will discuss the pathophysiology of infection in older adults, including specific infections such as cutaneous candidiasis, necrotizing soft tissue infection, osteomyelitis, and infections involving hardware.

Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are bone resorbing cells that are often increased in bone infected with S. aureus. The cytokine RANKL is essential for osteoclast formation under physiological conditions but in vitro evidence suggests that inflammatory cytokines may by-pass the requirement for RANKL. The goal of this study was to determine whether RANKL-dependent osteoclast formation is essential for the bone loss that occurs in a murine model of S. aureus osteomyelitis. To this end, humanized-RANKL mice were infected by direct inoculation of S. aureus into a unicortical defect in the femur. Mice were treated with vehicle or denosumab, a human monoclonal antibody that inhibits RANKL, both before and during a 14-day infection period. The severe cortical bone destruction caused by infection was completely prevented by denosumab administration even though the bacterial burden in the femur was not affected. Osteoclasts were abundant near the inoculation site in vehicle-treated mice but absent in denosumab-treated mice. In situ hybridization demonstrated that S. aureus infection potently stimulated RANKL expression in bone marrow stromal cells. The extensive reactive bone formation that occurs in this osteomyelitis model was also reduced by denosumab administration. Lastly, there was a notable lack of osteoblasts near the infection site suggesting that the normal coupling of bone formation to bone resorption was disrupted by S. aureus infection. These results demonstrate that RANKL-mediated osteoclast formation is required for the bone loss that occurs in S. aureus infection and suggest that disruption of the coupling of bone formation to bone resorption may also contribute to bone loss in this condition.

UNASSIGNED: Fournier\'s gangrene is a urological emergency associated with high mortality and morbidity. Severe gangrene resulting in pelvic bone and lower limb involvement are extremely rare.
METHODS: We report a rare case of Fournier\'s gangrene that is complicated by necrotising fasciitis of the lower limb and osteomyelitis of the pelvic bone, in a patient with previous prostatic adenocarcinoma. The patient was promptly resuscitated, started on broad spectrum antibiotics and then underwent an emergent surgical debridement, followed by multiple relook debridement and definitive reconstruction. Throughout the patient\'s hospitalisation, he was managed in a multidisciplinary team involving surgeons from different specialities, physicians and allied health staff.
UNASSIGNED: Extension of Fournier\'s gangrene into distant structures is rare but serious complications. To date, there is only one other case reported in literature. The relationship between prior prostatic malignancy and Fournier\'s gangrene can be explored in subsequent studies.
CONCLUSIONS: We present a rare case of Fournier\'s gangrene with pelvic and distal limb involvement. We highlight the possible yet devastating complications of this disease and discuss treatment options available for the holistic management of patients with Fournier\'s gangrene.

Infections associated with healthcare manipulations, particularly bloodstream infections stemming from catheters and medical devices, significantly heighten the probability of vertebral osteomyelitis. The diagnosis of infective endocarditis (IE) frequently overlaps with vertebral osteomyelitis (VO). In cases where individuals are suspected of having hematogenous vertebral osteomyelitis and have an intravascular catheter or device, it is recommended to undertake blood culture collection. We present a case of a 39-year-old male with a history of interventional AVM embolization and cerebral angiography, experiencing recurrent vertebral osteomyelitis. No definitive source of infection had been found, and transthoracic echocardiography (TTE) yielded negative results for IE. In Trans Esophageal Echocardiography (TEE), a retained micro-catheter extending from the aortic arch to the inguinal artery was discovered. Although we cannot definitively attribute the source of the osteomyelitis to the retained micro-catheter, no episodes of infection have been reported ever since. This case underscores the need to enhance our approaches and guidelines related to operating protocols in the surgical setting. Improving these guidelines can prevent similar occurrences in the future, emphasizing the importance of continuous improvement in healthcare practices.

UNASSIGNED: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.
UNASSIGNED: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.
UNASSIGNED: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up.
UNASSIGNED: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

UNASSIGNED: Dalbavancin is a long-acting lipoglycopeptide antibiotic that is increasingly utilized for infections that require prolonged treatment durations despite the lack of Food and Drug Administration approval for these indications. There is no consensus regarding optimal dosing of dalbavancin for these infections and no available pharmacokinetic studies to identify optimal dosing for long-term use.
UNASSIGNED: An in silico pharmacokinetic simulation was performed to assess the predicted dalbavancin concentration resulting from commonly utilized dosing regimens, in addition to modified regimens. The primary endpoint evaluated was days of median 24-hour free area under the curve over the minimum inhibitory concentration (AUC/MIC) >27.1, the established PK target.
UNASSIGNED: A dosing regimen of 1500 mg on day 0 and day 7 resulted in median AUC/breakpoint value above the target for 57 days (lower 95% confidence interval [CI], 37 days). A modified regimen of 1500 mg on day 0 and day 21 resulted in an additional 11 days of median AUC/breakpoint target attainment. The other standard dosing regimen modeled was 1000 mg on day 0, then 500 mg weekly for 5 doses. This regimen achieved the AUC/breakpoint target for 76 days (lower 95% CI, 59 days). This regimen was modified to 1000 mg on day 0, then 500 mg on days 14 and 28, which shortened the median effective treatment duration by 14 days but required 3 fewer doses.
UNASSIGNED: These simulated results, when combined with the favorable observational data, support the use of commonly reported dalbavancin regimens for prolonged therapy durations. In addition, these pharmacokinetic/pharmacodynamic data support extending the dosing interval beyond the frequently reported weekly regimens, which should be investigated further with a clinical trial.

OBJECTIVE: To develop and validate a modified deep learning (DL) model based on nnU-net for classifying and segmenting five-class jaw lesions using cone-beam computed tomography (CBCT).
METHODS: A total of 368 CBCT scans (37 168 slices) were used to train a multi-class segmentation model. The data underwent manual annotation by two oral and maxillofacial surgeons (OMSs) to serve as ground truth. Sensitivity, specificity, precision, F1-score, and accuracy were used to evaluate the classification ability of the model and doctors, with or without artificial intelligence assistance. The dice similarity coefficient (DSC), average symmetric surface distance (ASSD) and segmentation time were used to evaluate the segmentation effect of the model.
RESULTS: The model achieved the dual task of classifying and segmenting jaw lesions in CBCT. For classification, the sensitivity, specificity, precision, and accuracy of the model were 0.871, 0.974, 0.874 and 0.891, respectively, surpassing oral and maxillofacial radiologists (OMFRs) and OMSs, approaching the specialist. With the model\'s assistance, the classification performance of OMFRs and OMSs improved, particularly for odontogenic keratocyst (OKC) and ameloblastoma (AM), with F1-score improvements ranging from 6.2% to 12.7%. For segmentation, the DSC was 87.2% and the ASSD was 1.359 mm. The model\'s average segmentation time was 40 ± 9.9 s, contrasting with 25 ± 7.2 min for OMSs.
CONCLUSIONS: The proposed DL model accurately and efficiently classified and segmented five classes of jaw lesions using CBCT. In addition, it could assist doctors in improving classification accuracy and segmentation efficiency, particularly in distinguishing confusing lesions (e.g., AM and OKC).

UNASSIGNED: Neutrophil/lymphocyte ratio (NLR) and platelet/ lymphocyte ratio (PLR) are readily available and inexpensive biomarkers that have received great attention for diagnosing type 2 diabetes(T2DM) complications. The objective of the present cross-sectional study was to compare diagnostic values of these biomarkers with C-reactive protein(CRP) in detecting diabetic foot ulcer (DFU) and osteomyelitis (OS) and discriminating between the degree of DFU according to Wagner\'s classification.
UNASSIGNED: A total of 217 individuals (42 healthy controls, 40 T2DM patients without DFU, and 135 patients with DFU) were enrolled. The DFU patients were classified according to Wagner\'s classification into grade 1, grade 2, and grade 3. Blood samples were obtained and various biochemical and hematological parameters including creatine, CRP, HbA1c, NLR, and PLR were measured.
UNASSIGNED: The levels of CRP, PLR, and NLR were significantly higher in the patients with DFU and OS compared to healthy controls and T2DM patients without DFU. The median values of CRP were correlated with the severity of DFU and increased with DFU grades. The highest values of CRP, NLR, and PLR were observed in the DFU patients with OS which were significantly higher than those of DFU patients with grades 1 and 2 as well as T2DM patients without DFU. The PLR and NLR had no significant performance in diagnosing DFU patients with grades 1 and 2 from the patients without DFU.
UNASSIGNED: NLR and PLR could be useful for diagnosing OS but cannot be used for detecting lower grades of DFU. CRP showed higher performance in detecting OS compared to PLR and NLR.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01327-w.