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1.
Bone ; 187: 117181, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38960295

RESUMEN

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.


Asunto(s)
Resorción Ósea , Denosumab , Modelos Animales de Enfermedad , Osteoclastos , Osteomielitis , Ligando RANK , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Osteomielitis/microbiología , Osteomielitis/patología , Osteomielitis/metabolismo , Ligando RANK/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patología , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Ratones , Resorción Ósea/patología , Resorción Ósea/microbiología , Resorción Ósea/metabolismo , Denosumab/farmacología , Humanos , Fémur/patología , Fémur/microbiología , Anticuerpos Monoclonales Humanizados/farmacología
2.
Cell Mol Life Sci ; 81(1): 300, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39001897

RESUMEN

BACKGROUND: Age-associated impairments in innate immunity are believed to be a causative factor responsible for severe pathogenesis of Staphylococcus aureus (S. aureus) infection in the bone tissue. However, the basis for age-associated decline in innate immune response upon S. aureus infection remains poorly understood. RESULTS: Our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis show up-regulated CXCL9 and CXCL10 (CXCL9/10), which is further confirmed in vitro and in vivo by the present study. Notably, monocytes are a main source for CXCL9/10 production in bone marrow upon S. aureus challenge, but this response declines in middle-aged mice. Interestingly, conditional medium of bone marrow monocytes from middle-aged mice has a strikingly decreased effect on bactericidal functions of neutrophils and macrophages compares with that from young mice. We further show that activation of CXCL9/10-CXCR3 axis between monocytes and macrophages/neutrophils promotes the bactericidal function of the cells, whereas blocking the axis impairs such function. Importantly, treatment with either exogenous CXCL9 or CXCL10 in a middle-aged mice model enhances, while pharmacological inhibition of CXCR3 in young mice model impairs, bacterial clearance and bone marrow structure. CONCLUSIONS: These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes.


Asunto(s)
Quimiocina CXCL10 , Quimiocina CXCL9 , Modelos Animales de Enfermedad , Inmunidad Innata , Monocitos , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Osteomielitis/microbiología , Osteomielitis/inmunología , Osteomielitis/metabolismo , Osteomielitis/patología , Monocitos/inmunología , Monocitos/metabolismo , Quimiocina CXCL9/metabolismo , Quimiocina CXCL9/genética , Staphylococcus aureus/inmunología , Ratones , Quimiocina CXCL10/metabolismo , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Infecciones Estafilocócicas/metabolismo , Ratones Endogámicos C57BL , Receptores CXCR3/metabolismo , Receptores CXCR3/genética , Envejecimiento/inmunología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo
3.
Sci Rep ; 14(1): 12728, 2024 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830934

RESUMEN

To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4's inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.


Asunto(s)
Diferenciación Celular , N-Metiltransferasa de Histona-Lisina , Macrófagos , Células Madre Mesenquimatosas , Osteogénesis , Osteomielitis , Humanos , Osteomielitis/metabolismo , Osteomielitis/patología , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Macrófagos/metabolismo , Macrófagos/inmunología , Células Madre Mesenquimatosas/metabolismo , Células THP-1 , Técnicas de Cocultivo , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia
4.
J Biochem Mol Toxicol ; 38(7): e23753, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38923626

RESUMEN

Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus-induced mouse model of osteomyelitis. Femurs of S. aureus-infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme-linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate-resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation-associated genes in the femurs. The viability of human bone marrow-derived stem cells (hBMSCs) was determined using cell counting kit-8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling-related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus-induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus-induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus-stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus-infected mice and hBMSCs by activating Notch signaling.


Asunto(s)
Antibacterianos , Antiinflamatorios , Flavanonas , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Flavanonas/farmacología , Ratones , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Osteomielitis/metabolismo , Osteomielitis/patología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Humanos , Masculino , Osteogénesis/efectos de los fármacos , Fémur/patología , Fémur/metabolismo , Fémur/microbiología , Fémur/efectos de los fármacos
5.
Free Radic Biol Med ; 222: 122-129, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38848785

RESUMEN

Osteomyelitis, a grave deep tissue infection primarily caused by Staphylococcus aureus, results in serious complications such as abscesses and sepsis. With the incidence from open fractures exceeding 30 % and prevalent antibiotic resistance due to extensive treatment regimens, there's an urgent need for innovative, antibiotic-free strategies. Photothermal therapy (PTT) and photodynamic therapy (PDT) renowned for generating localized reactive oxygen species (ROS), face limitations in penetration depth. To overcome this, our method combines the deep penetration attributes of medical microwaves (MW) with the synergistic effects of the ZnO/ZrO2 solid solution. Comprehensive in vitro and in vivo evaluations showcased the solid-solution's potent antibacterial efficacy and biocompatibility. The ZnO/ZrO2 solid solution, especially in a 7:3 M ratio, manifests superior microstructural characteristics, optimizing MW-assisted therapy. Our findings highlight the potential of this integrated strategy as a promising avenue in osteomyelitis management.


Asunto(s)
Microondas , Osteomielitis , Staphylococcus aureus , Circonio , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Osteomielitis/patología , Osteomielitis/terapia , Animales , Staphylococcus aureus/efectos de los fármacos , Circonio/química , Ratones , Humanos , Catálisis , Antibacterianos/farmacología , Antibacterianos/química , Fotoquimioterapia/métodos , Zinc/química , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Oxígeno/química , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Terapia Fototérmica/métodos , Pruebas de Sensibilidad Microbiana
6.
J Vasc Interv Radiol ; 35(6): 852-857.e1, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38613536

RESUMEN

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.


Asunto(s)
Discitis , Disco Intervertebral , Osteomielitis , Valor Predictivo de las Pruebas , Humanos , Osteomielitis/microbiología , Osteomielitis/patología , Discitis/microbiología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Disco Intervertebral/patología , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/microbiología , Anciano , Adulto , Biopsia , Biopsia Guiada por Imagen/efectos adversos , Radiografía Intervencional
7.
Int J Infect Dis ; 144: 107027, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38670483

RESUMEN

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies. METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis was performed to evaluate the factors associated with yield. RESULTS: A total of 570 biopsies performed on 527 patients were included. A histopathologic diagnosis of osteomyelitis was made in 68.4% (359 of 525) of biopsies, and microbiological cultures were positive in 29.6% (169 of 570). Elevated erythrocyte sedimentation rate was positively associated with a histopathologic diagnosis of osteomyelitis (odds ratio [OR] =1.96, P = 0.007) and positive cultures from bone cores (OR = 1.02, P ≤0.001) and aspirate (OR = 1.02, P ≤0.001). Increased total core length was positively associated with a histopathologic diagnosis of osteomyelitis (OR = 1.81, P = 0.013) and positive cultures from bone cores (OR = 1.65, P = 0.049). Clinical management was affected by ICNB in 37.5% (214 of 570) of cases. CONCLUSIONS: In this large cohort, ICNB yielded approximately 30% positive cultures and changed clinical management in over one-third of the patients.


Asunto(s)
Biopsia Guiada por Imagen , Osteomielitis , Humanos , Osteomielitis/diagnóstico , Osteomielitis/microbiología , Osteomielitis/patología , Osteomielitis/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Biopsia Guiada por Imagen/métodos , Femenino , Persona de Mediana Edad , Biopsia con Aguja Gruesa/métodos , Anciano , Adulto , Anciano de 80 o más Años , Columna Vertebral/patología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/microbiología , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/microbiología , Enfermedades de la Columna Vertebral/patología , Enfermedades de la Columna Vertebral/tratamiento farmacológico
8.
Int J Paleopathol ; 45: 35-45, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653101

RESUMEN

OBJECTIVE: This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in 16th- century Peru. MATERIALS: Extremely well-preserved human remains of two children who died between the ages of 1-2 years old, recovered from the circum-contact (∼1540 CE) cemetery in Huanchaco, Peru. METHODS: Macroscopic and radiographic analysis. RESULTS: Both individuals present with cortical thickening, symmetrical destructive lesions, metaphyseal expansion, perforations, exposure of the medullary cavity, resorption of metaphyseal ends and necrosis of the long bones, and deposited reactive new bone. These features are consistent with osteomyelitis variolosa and bacterial osteomyelitis. CONCLUSIONS: Three features of Individuals IG-124 and IG-493 suggest a highly consistent diagnosis of osteomyelitis variolosa: multiple skeletal lesions, the historical context of the area, and the high mortality rate of non-adults in the circum-contact cemetery. SIGNIFICANCE: Although viral infections are ubiquitous and well documented historically, their etiologies are often difficult to determine in archaeological populations. Orthopoxvirus variola (smallpox) is one of the many viruses whose archaeological impact is still under explored in skeletal remains. LIMITATIONS: The absence of smallpox in other children from the Huanchaco cemetery creates difficulty in ascertaining true prevalence rates or information on potential outbreaks. SUGGESTIONS FOR FURTHER RESEARCH: Further research analyzing aDNA from calculus and/or residues using a DIP-GC-MS method might create a better understanding of how smallpox spread through the region.


Asunto(s)
Viruela , Humanos , Viruela/historia , Viruela/patología , Perú , Historia del Siglo XVI , Lactante , Preescolar , Masculino , Osteomielitis/historia , Osteomielitis/patología , Paleopatología/métodos , Femenino , Cementerios/historia
11.
J Immunol ; 212(5): 844-854, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38231123

RESUMEN

Infection after fracture fixation (IAFF), a complex infectious disease, causes inflammatory destruction of bone tissue and poses a significant clinical challenge. miR-345-3p is a biomarker for tibial infected nonunion; however, the comprehensive mechanistic role of miR-345-3p in IAFF is elusive. In this study, we investigated the role of miR-345-3p in IAFF pathogenesis through in vivo and in vitro experiments. In vivo, in a rat model of IAFF, miR-345-3p expression was downregulated, accompanied by increased M1 macrophage infiltration and secretion of proinflammatory factors. In vitro, LPS induced differentiation of primary rat bone marrow-derived macrophages into M1 macrophages, which was attenuated by miR-345-3p mimics. miR-345-3p promoted M1 to M2 macrophage transition-it reduced the expression of cluster of differentiation (CD) 86, inducible NO synthase, IL-1ß, and TNF-α but elevated those of CD163, arginase-1, IL-4, and IL-10. MAPK kinase kinase 1 (MAP3K1), a target mRNA of miR-345-3p, was overexpressed in the bone tissue of IAFF rats compared with that in those of the control rats. The M1 to M2 polarization inhibited MAP3K1 signaling pathways in vitro. Conversely, MAP3K1 overexpression promoted the transition from M2 to M1. miR-345-3p significantly inhibited NF-κB translocation from the cytosol to the nucleus in a MAP3K1-dependent manner. In conclusion, miR-345-3p promotes the polarization of M1 macrophages to the M2 phenotype by inhibiting the MAP3K1 and NF-κB pathways. These findings provide insight into the pathogenesis and immunotherapeutic strategies for IAFF and offer potential new targets for subsequent research.


Asunto(s)
MicroARNs , Osteomielitis , Ratas , Animales , FN-kappa B/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Transducción de Señal , Osteomielitis/patología
12.
Stomatologiia (Mosk) ; 102(6. Vyp. 2): 68-72, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-38096398

RESUMEN

The pandemic of coronavirus infection existed from 2019 to 2023. The World Health Organization (WHO) has announced on May 5, 2023 that the pandemic had ended. However, it does not cease to have an adverse effect on the health of the world population. Necrotic lesions of the bones of the facial skeleton are now a characteristic sign of a severe coronavirus infection. We conducted a review of scientific publications that reflected the relationship between coronavirus and necrotic processes of the skull bones, methods of treatment, prevention and the latest developments in this direction. The purpose of this article is to review existing studies on Post-Covid osteomyelitis of facial bones, its impact, features of the clinical picture of this disease, analysis of methods and means of treatment of this group of patients. Analysis of literature data has shown that the search for an ideal dressing material continues, especially the developments of native developers stand emphasized. The advantages of modern materials over traditional ones have become unquestionable, but further research in this direction is required.


Asunto(s)
COVID-19 , Huesos Faciales , Osteomielitis , Humanos , COVID-19/complicaciones , Huesos Faciales/patología , Osteomielitis/etiología , Osteomielitis/patología , Necrosis
14.
Orphanet J Rare Dis ; 18(1): 206, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37480122

RESUMEN

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans. METHODS: A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring. RESULTS: 36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments. CONCLUSIONS: Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.


Asunto(s)
Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Osteomielitis , Niño , Adulto , Humanos , Osteítis/diagnóstico , Osteítis/tratamiento farmacológico , Pamidronato/uso terapéutico , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/patología , Hiperostosis/tratamiento farmacológico , Inflamación
15.
J Rheumatol ; 50(10): 1333-1340, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37399459

RESUMEN

OBJECTIVE: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. METHODS: Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. RESULTS: One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. CONCLUSION: The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.


Asunto(s)
Investigación sobre la Eficacia Comparativa , Osteomielitis , Niño , Adulto Joven , Humanos , Estudios de Factibilidad , Estudios Prospectivos , Osteomielitis/tratamiento farmacológico , Osteomielitis/patología , Enfermedad Crónica
16.
Immunity ; 56(7): 1485-1501.e7, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37315560

RESUMEN

The interleukin 1 (IL-1) pathway signals through IL-1 receptor type 1 (IL-1R1) and emerges as a central mediator for systemic inflammation. Aberrant IL-1 signaling leads to a range of autoinflammatory diseases. Here, we identified a de novo missense variant in IL-1R1 (p.Lys131Glu) in a patient with chronic recurrent multifocal osteomyelitis (CRMO). Patient PBMCs showed strong inflammatory signatures, particularly in monocytes and neutrophils. The p.Lys131Glu substitution affected a critical positively charged amino acid, which disrupted the binding of the antagonist ligand, IL-1Ra, but not IL-1α or IL-1ß. This resulted in unopposed IL-1 signaling. Mice with a homologous mutation exhibited similar hyperinflammation and greater susceptibility to collagen antibody-induced arthritis, accompanied with pathological osteoclastogenesis. Leveraging the biology of the mutation, we designed an IL-1 therapeutic, which traps IL-1ß and IL-1α, but not IL-1Ra. Collectively, this work provides molecular insights and a potential drug for improved potency and specificity in treating IL-1-driven diseases.


Asunto(s)
Osteomielitis , Receptores de Interleucina-1 , Ratones , Animales , Receptores de Interleucina-1/genética , Osteomielitis/tratamiento farmacológico , Osteomielitis/genética , Osteomielitis/patología , Inflamación/genética , Inflamación/patología , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Transducción de Señal , Mutación
17.
Eur J Radiol ; 165: 110916, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37300936

RESUMEN

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Neoplasias Primarias Secundarias , Neoplasias , Osteomielitis , Osteonecrosis , Osteorradionecrosis , Humanos , Osteorradionecrosis/diagnóstico por imagen , Osteorradionecrosis/etiología , Osteorradionecrosis/patología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico por imagen , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Estudios Retrospectivos , Esclerosis/patología , Osteonecrosis/patología , Tomografía Computarizada de Haz Cónico , Neoplasias/patología , Neoplasias Primarias Secundarias/patología , Osteomielitis/diagnóstico por imagen , Osteomielitis/etiología , Osteomielitis/patología , Maxilares/diagnóstico por imagen , Maxilares/patología
18.
Int J Mol Sci ; 24(11)2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37298718

RESUMEN

Osteomyelitis is an infection of the bone that is often difficult to treat and causes a significant healthcare burden. Staphylococcus aureus is the most common pathogen causing osteomyelitis. Osteomyelitis mouse models have been established to gain further insights into the pathogenesis and host response. Here, we use an established S. aureus hematogenous osteomyelitis mouse model to investigate morphological tissue changes and bacterial localization in chronic osteomyelitis with a focus on the pelvis. X-ray imaging was performed to follow the disease progression. Six weeks post infection, when osteomyelitis had manifested itself with a macroscopically visible bone deformation in the pelvis, we used two orthogonal methods, namely fluorescence imaging and label-free Raman spectroscopy, to characterise tissue changes on a microscopic scale and to localise bacteria in different tissue regions. Hematoxylin and eosin as well as Gram staining were performed as a reference method. We could detect all signs of a chronically florid tissue infection with osseous and soft tissue changes as well as with different inflammatory infiltrate patterns. Large lesions dominated in the investigated tissue samples. Bacteria were found to form abscesses and were distributed in high numbers in the lesion, where they could occasionally also be detected intracellularly. In addition, bacteria were found in lower numbers in surrounding muscle tissue and even in lower numbers in trabecular bone tissue. The Raman spectroscopic imaging revealed a metabolic state of the bacteria with reduced activity in agreement with small cell variants found in other studies. In conclusion, we present novel optical methods to characterise bone infections, including inflammatory host tissue reactions and bacterial adaptation.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Infecciones Estafilocócicas , Ratones , Animales , Staphylococcus aureus/fisiología , Osteomielitis/patología , Modelos Animales de Enfermedad , Inflamación , Infecciones Estafilocócicas/microbiología , Infección Persistente
19.
Pediatr Radiol ; 53(10): 2092-2103, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37204463

RESUMEN

BACKGROUND: Spinal lesions in pediatric chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis (CRMO/CNO) can cause permanent sequelae; thus, early recognition of these is vital for management. OBJECTIVE: To characterize the MR imaging features and patterns of pediatric spinal CRMO/CNO. MATERIALS AND METHODS: This cross-section study received IRB approval. The first available MRI with documented spine involvement in children with CRMO/CNO was reviewed by a pediatric radiologist. Descriptive statistics were used to describe the characteristics of vertebral lesions, disc involvement, and soft tissue abnormality. RESULTS: Forty-two patients were included (F:M, 30:12); median age was 10 years (range 4-17). At diagnosis, 34/42 (81%) had spine involvement. Kyphosis in 9/42 (21%) and scoliosis in 4/42 (9.5%) patients were present at the time of spinal disease recognition. Vertebral involvement was multifocal in 25/42 (59.5%). Disc involvement was found in 11/42 (26%) patients, commonly in the thoracic spine and often with adjacent vertebrae height loss. Posterior element abnormalities were present in 18/42 patients (43%) and soft tissue involvement in 7/42 (17%). One hundred nineteen vertebrae were affected, commonly the thoracic vertebrae (69/119; 58%). Vertebral body edema was focal in 77/119 (65%) and frequently superior (42/77; 54%). Sclerosis and endplate abnormality were present in 15/119 (13%) and 31/119 (26%) vertebrae, respectively. Height loss was present in 41/119 (34%). CONCLUSION: Chronic non-bacterial osteomyelitis of spine is usually thoracic. Vertebral body edema is often focal at the superior vertebral body. Kyphosis and scoliosis occur in a quarter and vertebral height loss in a third of children at spinal disease recognition.


Asunto(s)
Cifosis , Osteomielitis , Escoliosis , Humanos , Niño , Preescolar , Adolescente , Osteomielitis/diagnóstico por imagen , Osteomielitis/patología , Columna Vertebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Cifosis/patología , Edema/patología
20.
Br J Radiol ; 96(1148): 20220758, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37102777

RESUMEN

OBJECTIVES: Our study used a radiomics method to differentiate bone marrow signal abnormality (BMSA) between Charcot neuroarthropathy (CN) and osteomyelitis (OM). METHODS AND MATERIALS: The records of 166 patients with diabetic foot suspected CN or OM between January 2020 and March 2022 were retrospectively examined. A total of 41 patients with BMSA on MRI were included in this study. The diagnosis of OM was confirmed histologically in 24 of 41 patients. We clinically followed 17 patients as CN with laboratory tests. We also included 29 nondiabetic patients with traumatic (TR) BMSA on MRI as the third group. Contours of all BMSA on T 2 - and T1 -weighted images in three patient groups were segmented semi-automatically on ManSeg (v.2.7d). The T1 and T2 features of three groups in radiomics were statistically evaluated. We applied the multi-class classification (MCC) and binary-class classification (BCC) methodologies to compare results. RESULTS: For MCC, the accuracy of Multi-Layer Perceptron (MLP) was 76.92% and 84.38% for T1 and T2, respectively. According to BCC, for CN, OM, and TR BMSA, the sensitivity of MLP is 74%, 89.23%, and 76.19% for T1, and 90.57%, 85.92%, 86.81% for T2, respectively. For CN, OM, and TR BMSA, the specificity of MLP is 89.16%, 87.57%, and 90.72% for T1 and 93.55%, 89.94%, and 90.48% for T2 images, respectively. CONCLUSION: In diabetic foot, the radiomics method can differentiate the BMSA of CN and OM with high accuracy. ADVANCES IN KNOWLEDGE: The radiomics method can differentiate the BMSA of CN and OM with high accuracy.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Osteomielitis , Humanos , Pie Diabético/complicaciones , Pie Diabético/diagnóstico por imagen , Diagnóstico Diferencial , Estudios Retrospectivos , Osteomielitis/diagnóstico por imagen , Osteomielitis/patología , Médula Ósea/patología , Diabetes Mellitus/patología
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