Simulation study of turning-ultrasonic rolling compound processing for 42CrMo steel.

The ultrasonic rolling processing technology has been shown to significantly reduce surface roughness and enhance the residual stress of parts, thereby improving their surface properties and extending their service life. This technology is particularly effective for the precision machining and surface strengthening of ultra-high-strength steel 42CrMo. This study aims to investigate the impact of turning pre-processing on the distribution of residual stress during ultrasonic rolling, a simulation model incorporating turning pre-processing was developed and used to conduct ultrasonic rolling simulation experiments, enabling the analysis of residual stress distribution patterns. Concurrently, ultrasonic rolling strengthening experiments were performed to validate the accuracy of the simulation model. The results confirm that with increasing rotational speed and feed rate, residual stress decreases, whereas with increasing static pressure and amplitude, residual stress increases. The residual stress variation obtained from the simulation of combined turning and ultrasonic rolling closely matched the results of experimental ultrasonic rolling tests. This consistency validates the accuracy of the simulation model. This study offers a novel approach for simulating and experimentally validating ultrasonic rolling processes, particularly for shaft-like parts that undergo turning as a pre-processing step.

A rare adult presentation of chronic recurrent multifocal osteomyelitis (CRMO) in 38-year female with exclusive spinal involvement.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder most often seen in children and adolescents characterized by recurrent episodes of sterile osteolytic osseous lesions. Diagnosing CRMO requires the exclusion of other conditions, which is often challenging due to its varied presentations and progression. However, adult-onset CRMO and exclusive spinal cases are extremely rare events, highlighting the importance of this case. Our case presents a 38-year-old female with chronic back pain for 6 months of postepidural anesthesia during a C-section. The pain was progressive, exacerbated by movement, and partially relieved by painkillers. The patient had tenderness on physical examination in the thoracolumbar region. MRI of the spine showed multiple endplate changes, and extensive laboratory tests and biopsy ruled out infectious cause and malignancy, leading to the diagnosis of CRMO. The connection between pain and epidural anesthesia was only an incidental finding. The patient was treated effectively with steroids and etanercept. CRMO is mainly a childhood disease, with adult cases being very rare. Isolated spinal involvement in CRMO is particularly rare and can make the diagnosis challenging. This case highlights that CRMO should be considered in adults with an atypical isolated spinal lesion. NSAIDs are the main treatment, with corticosteroids and TNF inhibitors used in unresponsive cases. This case underscores the need for heightened awareness of CRMO's potential to present in adults with atypical isolated spinal lesions, which could lead to more timely and accurate diagnoses.

Pamidronate for pain in adult chronic nonbacterial osteitis: protocol of a randomized, double-blind, placebo-controlled trial.

Chronic nonbacterial osteitis (CNO) is a rare auto-inflammatory bone disease affecting children and adults. Adult CNO is characterized by painful bone lesions, primarily of the anterior chest wall. There is no approved therapy for adult CNO. Current off-label treatments include intravenous bisphosphonates, which have been shown to alleviate pain through decreasing bone turnover. However, no adequately powered randomized controlled trials (RCTs) have been conducted. This double-blind, placebo-controlled RCT investigates the efficacy of intravenous pamidronate to decrease bone pain in adult CNO patients. Recruiting at the Dutch national referral center for CNO, adult patients with persistent bone pain despite non-steroidal anti-inflammatory drugs, or optionally other standard-of-care treatments are randomized to receive two courses of intravenous pamidronate (at 0 and 3 mo, 30 mg daily, on 3 consecutive d) or placebo. From 6 mo onwards, all patients receive open-label pamidronate for another two courses. The primary outcome is change in score for maximum pain from 0 to 6 mo. Secondary outcomes include change in quantitative intralesional bone turnover as measured on sodium-fluoride positron emission computed tomography ([18F]NaF-PET/CT), inflammation markers, shoulder function, general health, quality of life, fatigue, physical, and work activity. The pamidronate for pain in adult chronic nonbacterial osteitis trial addresses the need for evidence-based treatments in adult CNO. Results will directly impact daily clinical practice, either validating the use of intravenous pamidronate in CNO at the dose used in this trial or prompting the search for alternative regimens or agents. This trial was registered in EudraCT (reference 2020-001068-27) and the Dutch Trial Register (reference NL68020.058.20).

Analysis of the Suitability of Ultrasonic Testing for Verification of Nonuniform Welded Joints of Austenitic-Ferritic Sheets.

The purpose of the presented research was to determine the suitability of using ultrasonic testing (UT) to inspect heterogeneous, from a material point of view, welded joints on the example of the joints of a ferritic steel element with elements made of an austenitic steel. The echo technique with transverse (SEK) and longitudinal wave heads (SEL) addressed this issue. Due to the widespread use of 13CrMo4-5 and X2CrNiMo17-12-2 steel grades in the energy industry, they were selected as the test materials for the study. The objects of the presented research were welded joint specimens with thicknesses of 8, 12, and 16 mm and dimensions of 300 × 300 mm, made using the 135 metal active gas (MAG) process with the use of the Lincoln 309LSi wire-a ferritic-austenitic filler material. The stages of the research task were (1) making distance-amplitude curve (DAC) patterns from the test materials; (2) preparation of specimens of welded joints with artificial discontinuities in the form of through-holes; (3) performing UT tests on welded joints with artificial discontinuities using heads with 60° and 70° angles for the transverse wave and angle heads for longitudinal waves with similar beam insertion angles; (4) selection, by radiographic testing (RT), of welded joint specimens with natural discontinuities in the form of a lack of sidewall fusion; (5) performing UT tests on welded joints with natural discontinuities, using heads as welded joints with artificial discontinuities. It was found that (1) the highest sensitivity of discontinuity detection was obtained by performing tests on the ferritic steel side, which is due to the lower attenuation of the ultrasonic wave propagating in ferritic steel compared to austenitic steel; (2) the best detection of discontinuities could be obtained using a longitudinal ultrasonic wave; (3) there is a relationship between the thickness of the welded elements, the angle of the ultrasonic beam introduction, and the effectiveness of discontinuity detection.

An improved understanding of pediatric chronic nonbacterial osteomyelitis pathophysiology informs current and future treatment.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and young people. It can cause significant pain, reduced function, bone swelling, and even (vertebral body) fractures. Because of a limited understanding of its pathophysiology, the treatment of CNO remains empiric and is based on relatively small case series, expert opinion, and personal experience. Several studies have linked pathological NOD-kike receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation and the resulting imbalance between pro- and anti-inflammatory cytokine expression with CNO. This agrees with elevated pro-inflammatory (mostly) monocyte-derived protein signatures in the blood of CNO patients that may be used as future diagnostic and/or prognostic biomarkers. Recently, rare variants in the P2RX7 gene, encoding for an ATP-dependent transmembrane channel, were linked with increased NLRP3 inflammasome assembly and prolonged monocyte/macrophage survival in CNO. Although the exact molecular mechanisms remain unclear, this will inform future target-directed and individualized treatment. This manuscript reviews most recent developments and their impact on diagnostic and therapeutic strategies in CNO.

Chronic nonbacterial osteomyelitis (CNO) is a rare bone disease. Most reports are from children and young people, but adults can also be affected and may, indeed, be underreported in the literature. In CNO, the bone becomes inflamed and swollen, which can cause significant pain, deformity, and fractures. The disease is difficult to diagnose and treat because there are no good tests or approved treatments. Recently, a pronounced overactivation of inflammation has been linked with CNO. Especially the production and release of inflammatory proteins are increased. This causes the activation of bone eating cells ("osteoclasts") and bone inflammation. Although the exact mechanisms behind this remain somewhat unclear, a growing understanding of CNO accelerates the development of new treatments. This manuscript summarizes our current knowledge of CNO with a focus on children and young people. It discussed how a better understanding of disease mechanisms influences available and future treatment.

Strength and Fracture Toughness of TIG- and Laser-Welded Joints of Low Carbon Ferritic Steels.

This paper presents the results of experimental testing of joints welded using conventional TIG and laser methods. The welded components were sheets of the low-carbon steels 13CrMo4-5 and 16Mo3. Welded joints were made using different levels of linear welding energy. In the case of laser welding, a bifocal beam with longitudinal positioning of the focal lengths in relation to the welding direction was used. Experimental tests on welded joints included a bending test and determination of hardness distribution, mechanical properties, and fracture toughness, as well as microstructural research in the material of the various joint zones. Based on the determined strength characteristics, the true stress-strain relationships were defined, and a numerical model of the laser joints was developed in Abaqus 6.12-3. The modelled joint was subjected to loading to determine the most stressed areas of the joints. The numerical results were compared with those obtained using GOM's Aramis 3D 5M digital image correlation system. The system used made it possible to record displacements on the surface of the analysed joints in real time. Good agreement was obtained between the strain fields calculated numerically and those recorded using the Aramis 3D 5M video system. The numerical calculations provided information on the strains and stresses occurring inside the analysed joint during loading. It was found that the welded joints were characterised by increased hardness and high strength properties in relation to the base material. The bending test of the laser-welded joints gave a positive result-no cracks were observed on the face or root of the weld. The fracture toughness of the joint zones is slightly lower in relation to that of the base material, but no brittle fracture was observed.

Incidence of chronic recurrent multifocal osteomyelitis in children and adolescents in the UK and Republic of Ireland.

OBJECTIVES: Chronic Recurrent Multifocal Osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis (CNO), is a rare autoinflammatory condition affecting the bones in children and teenagers. The actual incidence of CRMO remains uncertain. The objective of this study is to identify the incidence of CRMO in children and young people under the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). We also aim to delineate the demographics, clinical presentation, investigations, initial management and healthcare needs for children and adolescents with CRMO. METHODS: We conducted monthly surveys among all paediatric consultants and paediatric orthopaedic surgeons to identify patients newly diagnosed with CRMO between October 2020 and November 2022. A standardised questionnaire was sent to reporting clinicians to collect further information. RESULTS: Over the surveillance period, 288 patients were reported, among which, 165 confirmed and 20 probable cases were included in the analysis. The highest incidences were among 8-10 year-olds. A two-to-one female-to-male difference in incidence was observed, and male patients were more likely to present with multifocal disease. A negative correlation was observed between reporting clavicular and leg pain. Investigation-wise, 80.0% of patients were reported to have undergone whole-body MRI and 51.1% had bone biopsies. The most common initial treatments were NSAIDs (93.9%) and bisphosphonates (44.8%). CONCLUSION: This study estimates an average annual CRMO incidence of 0.65 cases per 100 000 children and adolescents in the UK and ROI. These findings establish a crucial baseline for ongoing research and improvement in the care of individuals with CRMO.

Pediatric SAPHO syndrome with pleural effusion: case report of a unique finding in a rare disease.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by bone inflammation and skin manifestations including acne, palmoplantar pustulosis, psoriasis, or hidradenitis suppurativa. SAPHO syndrome is considered on the same spectrum as chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis (CNO/CRMO), the former often being the nomenclature in adults and the latter in children. The diagnosis is made on patterns of clinical manifestations and is a diagnosis of exclusion. While skin and bone manifestations are commonly described with SAPHO syndrome, pleural involvement is rare, and few cases have been described in the literature, especially in pediatric patients. Herein we present a 14-year-old female with a past medical history of hidradenitis supprtiva, eczema, psoriasis, and a prior episode of culture-negative osteomyelitis who presented to the emergency room with chief complaints of right sided pain with inspiration and back pain. Exam revealed palmoplantar pustulosis, hidradenitis supprativa, psoriasis, and tenderness of vertebrae. Imaging showed a right sided pleural effusion and multiple sites of osteitis. Laboratory evaluation revealed elevated inflammatory markers, an exudative pleural effusion with neutrophilic predominance, and no evidence of malignancy, infection, or immunodeficiency. The patient was diagnosed with SAPHO syndrome and treated with naproxen, methotrexate, and golimumab with significant improvement including resolution of the pleural effusion. Pediatric SAPHO syndrome is a rare disease that classically causes osteitis and skin manifestations. This case highlights that pleural effusion can be a rare manifestation of pediatric SAPHO syndrome. Patients with suspected SAPHO syndrome with respiratory symptoms should be evaluated for pleural effusion.

[Arthritis and osteomyelitis in childhood and adolescence-Bacterial and nonbacterial]. / Arthritis und Osteomyelitis im Kindes- und Jugendalter ­ bakteriell und nichtbakteriell.

Bacterial arthritis and osteomyelitis are usually acute diseases, which in this way differ from the often insidious course of nonbacterial osteomyelitis; however, there is often an overlap both in less acute courses of bacterial illnesses and also in nonbacterial osteitis. The overlapping clinical phenomena can be explained by similar pathophysiological processes. In bacteria-related illnesses the identification of the pathogen and empirical or targeted anti-infectious treatment are prioritized, whereas no triggering agent is known for nonbacterial diseases. The diagnostics are based on the exclusion of differential diagnoses, clinical scores and magnetic resonance imaging (MRI). An activity-adapted anti-inflammatory treatment is indicated.

Collaborative approach to paediatric chronic non-bacterial osteomyelitis of the mandible: Great Ormond Street Hospital case series.

This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings highlight the homogeneous presenting signs and symptoms of an intermittently painful, swollen angle and ramus of the mandible. We present the typical laboratory investigative findings (normal inflammatory markers) and imaging appearances (sclerosis and periosteal oedema). Our paper outlines an investigation protocol, including recommendations for extraoral bone biopsies and systemic magnetic resonance imaging (MRI). We explain the importance of multidisciplinary care, with combined care by rheumatologists and infectious disease specialists. Finally we demonstrate the efficacy of our treatment algorithm for oral non-steroidal anti-inflammatory drugs (NSAIDs), and in those cases refractory to NSAIDS, intravenous pamidronate. This paper provides a useful addition to the literature by informing OMF surgeons of this rare condition and given the clinical equipoise in treatments, it can hopefully guide clinicians in an investigation pathway and management protocol.

Chronic non-bacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO) with a focus on pamidronate therapy.

Chronic recurrent multifocal osteomyelitis (CRMO), also called chronic nonbacterial osteomyelitis (CNO) or nonbacterial osteomyelitis (NBO), is a rare autoinflammatory bone disease of unknown etiology. However, the number of patients properly diagnosed would increase with better knowledge of the disease. In this regard, whole-body magnetic resonance imaging (WB MRI) has been found to be a better predictor of active lesions than clinical examination. Importantly, the RINBO index (radiologic index for NBO) quantifies the involvement based on the WB MRI. Further, a chronic nonbacterial osteomyelitis MRI scoring (CROMRIS) has been developed as an online tool for assessing WB MRI. The therapy consists of non-steroidal anti-inflammatory drugs (NSAIDs), bisphosphonates (pamidronate, zoledronate, etc.) and other drugs, including biologics. Pamidronate is an appropriate and safe therapy. The first pilot prospective randomised controlled trial (RCT) on pamidronate vs. placebo was carried out in adults. No RCT has been done in children yet. Besides RCTs, there are a number of issues to be explored in future, i.e. predictors of therapy effect, optimal therapy duration, predictors of therapy discontinuation and evaluation of optimal therapy protocol. Recently, the CNO clinical disease activity score (CDAS) was constructed and validated but the classification criteria are still being developed. As collaboration on this rare disease is essential, a prospective Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) was established to generate future comparative effectiveness research data.

Geriatric chronic recurrent multifocal osteomyelitis (CRMO) mimicking multifocal multiple myeloma: a first in an octogenarian.

Chronic recurrent multifocal osteomyelitis (CRMO), an autoinflammatory bone disorder characterized by non-bacterial osteomyelitis causing recurrent multifocal bone lesions, is a well-known, yet uncommon pediatric condition that rarely affects adults; to date, it has never been diagnosed over the age of 75. The following report will discuss the first octogenarian diagnosed with CRMO and therefore represents an exceptionally rare presentation of a rare disease. An 83-year-old woman presented with progressive right shoulder, forearm, and hip pain, with associated weight loss and global weakness, requiring a wheelchair for mobility. Imaging revealed a pathologic right ulna fracture in addition to lytic lesions of the right proximal humerus and proximal femur. The clinical picture was thus that of a patient with probable multiple myeloma versus metastatic disease. After an extensive workup, however, the lesions were not malignant; histologic findings were instead suggestive of chronic osteomyelitis with negative cultures. Given the multifocal nature of this condition, combined with a lack of clinical symptoms of infection, a diagnosis of CRMO was rendered. The patient underwent intramedullary nailing of the right femur and splinting of the ulna, with a subsequent remarkable recovery to painless ambulation, complete union of the right ulna fracture, and resolution of the lytic lesions without receiving any targeted medical treatment. This case highlights the importance of maintaining CRMO on the differential for multifocal skeletal lesions, regardless of age. Performing a thorough workup with necessary imaging, biopsy, and culture are critical to establishing this diagnosis, which can only made as a diagnosis of exclusion.

A statistical symptomatic evaluation on SAPHO syndrome from 56 cases of confirmed diagnosis and 352 cases of non-SAPHO involvement.

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome. METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed. RESULT: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores. CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO), an autoinflammatory bone disease primarily affecting children, can cause pain, hyperostosis and fractures, affecting quality-of-life and psychomotor development. This study investigated CNO-associated variants in P2RX7, encoding for the ATP-dependent trans-membrane K+ channel P2X7, and their effects on NLRP3 inflammasome assembly. Whole exome sequencing in two related transgenerational CNO patients, and target sequencing of P2RX7 in a large CNO cohort (N = 190) were conducted. Results were compared with publicly available datasets and regional controls (N = 1873). Findings were integrated with demographic and clinical data. Patient-derived monocytes and genetically modified THP-1 cells were used to investigate potassium flux, inflammasome assembly, pyroptosis, and cytokine release. Rare presumably damaging P2RX7 variants were identified in two related CNO patients. Targeted P2RX7 sequencing identified 62 CNO patients with rare variants (32.4%), 11 of which (5.8%) carried presumably damaging variants (MAF <1%, SIFT "deleterious", Polyphen "probably damaging", CADD >20). This compared to 83 of 1873 controls (4.4%), 36 with rare and presumably damaging variants (1.9%). Across the CNO cohort, rare variants unique to one (Median: 42 versus 3.7) or more (≤11 patients) participants were over-represented when compared to 190 randomly selected controls. Patients with rare damaging variants more frequently experienced gastrointestinal symptoms and lymphadenopathy while having less spinal, joint and skin involvement (psoriasis). Monocyte-derived macrophages from patients, and genetically modified THP-1-derived macrophages reconstituted with CNO-associated P2RX7 variants exhibited altered potassium flux, inflammasome assembly, IL-1ß and IL-18 release, and pyroptosis. Damaging P2RX7 variants occur in a small subset of CNO patients, and rare P2RX7 variants may represent a CNO risk factor. Observations argue for inflammasome inhibition and/or cytokine blockade and may allow future patient stratification and individualized care.

The effects of oil-quenching and over-tempering heat treatments on the dry sliding wear behaviours of 25CrMo4 steel.

This study, it was aimed to examine the dry sliding wear properties of the tempering and over-tempering heat treatments of 25CrMo4 steel, which is used in the manufacture of parts such as axle shafts, axle sleeves, turbine parts, and turbine blades in the automotive industry Oil-quenched 25CrMo4 steels could be subjected to high temperatures where they are used and may undergo over-tempering period. In this case, there may be changes in many mechanical properties such as wear. For this purpose, microstructural examination, hardness, and dry sliding wear tests were performed on the materials. As a result of the tests, it was observed that the sample, on which we applied the tempering and over-tempering heat treatment, had a martensitic microstructure. The hardness values of the tempered and over-tempered samples increased compared to the raw material and as expected, partially decreased in the over-tempered sample. Dry sliding wear losses decreased significantly in oil-quenched and over-tempered samples compared to the raw material. Even though the hardness decreased in the over-tempered sample, the wear loss was low. The variation between wear losses increased further with the increase in friction forces. While the maximum friction coefficient was highest in the oil-quenched sample, it was lowest in the raw sample.

Adult-onset chronic recurrent multifocal osteomyelitis: a case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease predominantly affecting the metaphyses of long bones and is usually seen in children. Although CRMO is generally a pediatric disease, it may also occur in adults. This may result in a delay in the diagnosis of adult-onset CRMO. This report presents an adult-onset female patient who presented with left leg pain followed by swelling in the right knee. The patient was initially started on colchicine treatment, but, due to unresponsiveness in the follow-up the patient, the treatment was switched to a combination of methotrexate and prednisolone. A satisfactory clinical recovery was achieved with these drugs. CRMO could be considered in the differential diagnosis of patients presenting with bone pain and joint complaints. Considering that the disease progresses with clinical flare-ups and remission periods, it should be kept in mind that patients should be followed closely and treatment can be changed.

42CrMo4 steel flow behavior characterization for high temperature closed dies hot forging in automotive components applications.

The application of new forming processes as the high temperature hot forging in closed dies in an industrial environment still requires further investigation due to the lack of flow stress data at these temperatures. To determine the flow behavior of the 42CrMo4 steel at high temperatures hot compression tests have been carried out in a Gleeble® 3800 thermomechanical tester for a temperature range that covers the material behavior from the hot forging until the Nil Ductility Temperature (1250 °C-1375 °C) and for three different orders of magnitudes for the strain rates (0.1 s-1, 1 s-1 and 10 s-1). Then, the Hansel-Spittel model, widely used in automotive commercial software as FORGE®, has been employed to obtain the adequate constants of the constitutive equation for high temperatures. Finally, the newly obtained flow behavior model has been validated by comparison between experimental and simulated compression tests and by the process simulation of a commercial automotive component comparing the results of the simulation with the already made experimental tests in a laboratory cellule of the new technology. Hence, this paper shows the procedure for the determination and the obtention of a new constitutive model for the 42CrMo4 steel flow stress characterization at a temperature range between 1250 °C-1375 °C. This will contribute in the knowledge of material flow stress behavior models at high temperatures and will allow the prediction or simulation of high temperature hot forging in closed dies processes, enhancing the possibility of the application of these technologies from an industrial point of view.

Spinal Involvement in Patients with Chronic Non-Bacterial Osteomyelitis (CNO): An Analysis of Distinctive Imaging Features.

Spinal involvement by chronic non-bacterial osteomyelitis (CNO) has been increasingly reported in recent years, often being presented as a diagnostic dilemma requiring differential diagnosis with bacterial spondylodiscitis and/or neoplasia. This study was aimed at identifying the imaging features of CNO facilitating its differentiation from other spinal diseases. Two radiologists assessed the imaging studies of 45 patients (16 male and 29 female, aged from 6 to 75 years, 15 children) with CNO collected from 5 referential centers. Spinal lesions were found in 17 patients (2 children and 15 adults), most often in the thoracic spine. In children, the lesions involved short segments with a destruction of vertebral bodies. In adults, the main findings were prominent bone marrow edema and osteosclerosis, endplate irregularities, and ankylosing lesions extending over long segments; paraspinal inflammation was mild and abscesses were not observed. In both children and adults, the involvement of posterior elements (costovertebral and facet joints) emerged as an important discriminator between CNO and neoplasia/other inflammatory conditions. In conclusion, a careful inspection of imaging studies may help to reduce the number of biopsies performed in the diagnostic process of CNO.

Chronic Nonbacterial Osteomyelitis in Inflammatory Bowel Disease.

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition.

We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient's symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1ß, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.