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Inflammatory & Infectious

Primary spondylodiscitis: pathogen profiles, risk factors, and management of neurological deficits or spinal instability.

Overview

Local myofascitis of the deltoid muscle can occur after administration of the AstraZeneca (AZD1222) COVID-19 vaccine and may present as infectious or inflammatory [2]. For persistent symptoms suggestive of infection, blood tests and imaging should be performed, and empirical antibiotic administration should be considered [2]. Expert consultation with infectious disease specialists and clinical microbiologists is recommended for the use of antibiotics for individualized agents [3]. Adherence to principles of a high index of suspicion, correct interpretation of data, thorough surgery, optimization of host factors, and pathogen-specific antibiotic therapy will maximize the patient's prognosis in orthopedic infections [19].

Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in immunocompromised patients [42], with historically poor outcomes due to a lack of evidence-based treatment guidelines [42]. Patients' immune status may impact the diagnostic accuracy and risk of developing periprosthetic joint infection (PJI) [6], though there are limited prospective analyses and no clinical consensus on the best immunologic markers for assessing immune status in this context [6]. A universal definition for periprosthetic joint infection (PJI) has been proposed to standardize diagnosis and facilitate comparison of published evidence [20]. The optimal timing for reimplantation in two-stage exchange for hip and knee infections has not been established and should be based on clinical control of infection [45].

Early diagnosis, appropriate antimicrobial therapy, and surgical intervention when necessary are crucial for improving patient outcomes in spondylodiscitis [9]. Treatment of osteomyelitis of the pubis after strenuous exercise involves starting intravenous antibiotics early and continuing them for six weeks, with a high expectation that the infection will resolve [5]. The outcome of Kocuria species infections mainly depends on the type of infection and is higher for infective endocarditis [10]. Adhering to strict diagnostic and treatment algorithms while utilizing new classifications and scoring systems can predict patient outcomes and improve patient care and resource utilization in pediatric musculoskeletal infections, inflammatory disorders, and nonaccidental trauma [4]. Close outpatient follow-up is essential to ensure antibiotic compliance and to identify late consequences of pediatric musculoskeletal infection [7].

Anatomy & Pathophysiology

Osseous and Spinal Deformity

Untreated spinal infections can cause mechanical instability and possible neurologic compromise [12]. Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by back pain, spinal stiffness, and flowing ossification along the anterolateral margins of at least four contiguous vertebrae [92]. Structural changes of the spine are associated with metabolic syndrome in patients with psoriatic arthritis or ankylosing spondylitis [73]. Global kyphosis is significantly associated with functional status, spinal mobility, and quality of life in patients with ankylosing spondylitis [90]. Correction of spinal deformity at an early age is important [85], and surgery should be performed as early as possible to avert the development of severe local deformities and prevent secondary structural deformities that would require more extensive fusion later [94]. If diagnosis and treatment of spinal tuberculosis are delayed, spinal damage and other consequences might be incurable [89]. Percutaneous surgical treatment for thoracolumbar fractures in ankylosing spondylitis can improve pain, neurological function, and kyphotic deformity with effects similar to traditional methods [75].

Disc Pathology and Metabolism

Modic changes, particularly Type 2, are common radiological findings in lumbar spine imaging, most frequently occurring at L4/L5 and L5/S1 levels [80]. MicroRNAs are involved in extracellular matrix degradation, apoptosis, inflammation, and mechanobiology in degenerative disc pathology [81]. Overall bone metabolism of the operated intervertebral disc space at six weeks has the highest diagnostic accuracy for predicting fusion status at one year [88]. A combination of IDEAL and T2 mapping may provide deeper insights into the pathophysiological degeneration of paraspinal muscles in ankylosing spondylitis [78].

Kinematics and Soft Tissue

Posterior and posterior superior labral (PPS) injuries produce alterations in glenohumeral kinematics with implications for joint instability, increased joint loading, and potential joint damage [74]. Relatively low magnitude tensile stress might play an essential role in the anti-inflammatory process and the relief of low-back pain [87]. There is no need for additional training to improve postural control in adolescents with idiopathic scoliosis compared to healthy peers [91].

Neurologic and Traumatic Considerations

Preoperative planning for pedicle screw insertion in adolescent idiopathic scoliosis should be based on anatomical limitations in the apical vertebra region, apical vertebra level, and apical vertebral rotation degree [86]. Serious cervical spine injuries in football have not been eliminated, though rates have declined since the outlawing of spearing [96].

Classification

Expert Consultation: Expert consultation with infectious disease specialists and clinical microbiologists is recommended for the use of antibiotics for individualized agents [3]. Adhering to strict diagnostic and treatment algorithms while utilizing new classifications and scoring systems can predict patient outcomes and improve patient care and resource utilization in pediatric musculoskeletal infections [4].

Periprosthetic Joint Infection (PJI) Definitions: A universal definition for periprosthetic joint infection (PJI) has been proposed to standardize diagnosis and facilitate comparison of published evidence [20]. A new definition for periprosthetic joint infection (PJI) has been proposed to serve as a 'gold standard' that can be universally adopted by clinicians, surveillance authorities, and researchers to ensure consistency in diagnosis and management [60]. Proceedings from the International Consensus Meeting on Periprosthetic Joint Infection summarize discussions and recommendations aiming to standardize definitions, diagnosis, and treatment approaches for PJI [68]. The criteria for periprosthetic joint infection (PJI) are validated for chronic PJI in both hips and knees [69]. The criteria for periprosthetic joint infection (PJI) require further validation for acute infections and novel microbiological methods [69].

Temporal Classification: There is no evidence-based time interval that divides acute from chronic periprosthetic joint infection (PJI) [14]. The natural history of infection is a continuum from initiation to chronicity [14].

Treatment Algorithms: Two-stage exchange arthroplasty is the preferred treatment for chronic periprosthetic joint infection (PJI) [77]. Incision and débridement may be effective for acute periprosthetic joint infections (PJI) [77].

Other Considerations: Patients' immune status may impact the diagnostic accuracy and risk of developing periprosthetic joint infection (PJI) [6]. There are limited prospective analyses and no clinical consensus on the best immunologic markers for PJI risk assessment [6]. Infection outcomes for Kocuria species mainly depend on the type of infection, with higher outcomes observed for infective endocarditis [10]. Musculoskeletal infections vary substantially in their presentation and required treatment, which is based on the causative organism, the location of the infection, and the age of the patient [11]. Poor evidence suggests that COVID-19 could target the musculoskeletal system causing reactive arthritis at its post infectious stage [70]. Infections of the musculoskeletal system are common and challenging to treat [71]. Advancements in knowledge regarding bacterial evasion of host immunity, biofilm formation, and resistance offer new therapeutic targets including novel antimicrobial agents, immunotherapy, and dispersal agents [71]. Biofilm formation is central to the pathogenesis of medical device-associated infections [72]. Biofilm formation renders bacteria resistant to host defenses and antibiotic therapy [72]. Biofilm formation in medical device-associated infections often requires surgical removal of infected biomaterials [72]. There are significant differences in postoperative inpatient medical and orthopedic complications among different types of inflammatory arthropathies following total knee arthroplasty [76].

Clinical Presentation

Clinical suspicion for musculoskeletal infection must be maintained in patients with deteriorating conditions or poor responses to conservative treatment, as these findings indicate the need for meticulous surgical drainage and excision of infected and necrotic tissues [1]. Persistent symptoms following AstraZeneca (AZD1222) COVID-19 vaccine administration may represent local myofascitis of the deltoid muscle, requiring consideration of infection, blood tests, imaging, and empirical antibiotics [2]. Diagnosing pediatric musculoskeletal infections presents a specific challenge due to varying clinical presentations and symptoms that overlap with noninfectious diagnoses, necessitating prompt evaluation to avoid treatment delays [8]. Polyarticular septic arthritis in immunocompetent adults is a puzzling clinical condition frequently associated with delayed diagnosis [16].

Screening and Diagnostic Testing: CRP and ESR are the most commonly accepted screening tests for musculoskeletal infections with high sensitivity [33]. Combining serological tests improves diagnostic accuracy for musculoskeletal infections, though further work is required to identify the optimal combination [33]. However, diagnosis of periprosthetic joint infection (PJI) cannot be based solely on serological tests at this time [33]. Biopsies for giant cell arteritis are more likely to be positive and show characteristic histopathologic features in patients with high CRP and ESR levels prior to the start of corticosteroid treatment [18]. Pathologic examination should be performed alongside culture tests to accurately detect and identify bacteria in actinomycotic osteomyelitis, as the probability for culture confirmation is quite low [32]. Clinical suspicion for Kingella kingae infection should be maintained in young patients presenting atypically, and routine PCR testing is recommended [30]. Propionibacterium acnes should be considered a causative organism in bone and joint infections, particularly when the clinical picture is indolent and traditional diagnostic testing is negative [35].

Intraoperative and Special Considerations: Intraoperative findings, including sinus tracts, cell counts, frozen sections, and point-of-care diagnostic tests, must be communicated to infectious disease specialists to guide diagnosis and management [31]. Obtaining cultures for unusual pathogens and using susceptibility testing to guide antimicrobial therapy is important in immunosuppressed patients with Mycobacterium chelonae infection following silicone arthroplasty [34]. Early diagnosis of Mycobacterium bovis osteomyelitis allows for appropriate treatment modification, as pyrazinamide is ineffective against BCG [36]. Infection outcomes for Kocuria species mainly depend on the type of infection, with higher outcomes observed for infective endocarditis [10].

Management and Prognosis: Expert consultation with infectious disease specialists and clinical microbiologists is recommended for the use of antibiotics for individualized agents [3]. Adhering to strict diagnostic and treatment algorithms while utilizing new classifications and scoring systems can predict patient outcomes and improve care and resource utilization in pediatric musculoskeletal infections [4]. Diagnosing and managing pediatric musculoskeletal infections is challenging due to variable clinical presentations and severity, requiring orthopaedic surgeons to lead multidisciplinary teams to improve outcomes and ensure timely interventions [29]. Musculoskeletal infections vary substantially in presentation and required treatment, which is based on the causative organism, location of infection, and patient age [11]. Early diagnosis, appropriate antimicrobial therapy, and surgical intervention when necessary are crucial for improving outcomes in spondylodiscitis [9]. Untreated spinal infections can cause mechanical instability and possible neurologic compromise [12].

Investigations

Laboratory: Deterioration in clinical condition or poor response to conservative treatment necessitates meticulous surgical drainage and excision of infected and necrotic tissues [1]. Persistent symptoms following AstraZeneca COVID-19 vaccine administration warrant consideration of infection, blood tests, imaging, and empirical antibiotic administration [2]. Biopsies for giant cell arteritis yield characteristic histopathologic features with higher likelihood in patients presenting with high CRP and ESR levels [18]. These biopsies are also more likely to be positive prior to the initiation of corticosteroid treatment [18].

Plain radiography: Radiographic findings in chronic osteomyelitis were universally observed across all patients, demonstrating high concordance among specialists, with the exception of soft tissue swelling [52]. All available imaging modalities, including plain radiography, CT, MRI, and WBC scintigraphy, possess limited accuracy for identifying osteomyelitis and should not be utilized as standalone tests [37].

MRI: Early use of MRI delineates the extent of methicillin-resistant Staphylococcus aureus bone and joint infections in children, aiding surgical consideration and planning [41]. An MRI scan of the whole spine and pelvis is recommended for patients with methicillin-sensitive Staphylococcus aureus septicaemia presenting with back pain when the primary infection source is unidentified or clinical examination is unreliable [56]. Multifocal spondylodiscitis occurs in approximately 13% of cases, necessitating total spine MRI to avoid overlooking additional infection levels that impact therapeutic strategy [39]. Imaging methods including CT, MRI, and nuclear medicine techniques can demonstrate the extent of soft-tissue and bone involvement in periprosthetic joint infection and may help guide bone resection [40].

CT: CT-guided aspiration is an effective treatment for pyomyositis in HIV-positive patients presenting with painful and swollen muscles [59]. Imaging methods including CT, MRI, and nuclear medicine techniques can demonstrate the extent of soft-tissue and bone involvement in periprosthetic joint infection and may help guide bone resection [40].

Bone scan: The diagnostic effect of fluorine-18 fluorodeoxyglucose positron emission tomography for pyogenic spondylitis is superior in patients without previous spine surgery compared to postoperative cases [58]. Fluorine-18 fluorodeoxyglucose-positron emission tomography is highly accurate as a single technique for the evaluation of chronic musculoskeletal infections and is especially valuable for the central skeleton [63].

Other Considerations: Pediatric musculoskeletal infections present a diagnostic challenge due to varying clinical presentations and symptom overlap with noninfectious diagnoses, requiring prompt evaluation to avoid treatment delays [8]. Improvements in radiologic imaging and antibiotic treatment have led to earlier detection and decreased morbidity and mortality in acute hematogenous osteomyelitis in children [15]. Successful treatment of granulomatous vertebral osteomyelitis requires timely diagnosis, prompt medical management, and potential surgical intervention for neural decompression and correction of spinal malalignment [21]. Surgical intervention for removal of infected tissue and fusion may be required for Pseudomonas vertebral osteomyelitis in heroin addicts even in the absence of an abscess [57]. Physicians and radiologists should consider gouty spondylitis when encountering conditions mimicking infectious spondylodiscitis by combining imaging with patient history and clinical manifestations [61]. Early anti-inflammatory intervention may slow radiographic progression in ankylosing spondylitis patients based on preclinical mouse model observations [27].

Treatment

Non-Operative

Conservative management serves as the primary treatment for most patients with spondylodiscitis, though surgical intervention is indicated for doubtful diagnosis, progressive neurological deficits, progressive spinal deformity, failure to respond to treatment, and unresolved pain [48]. Treatment of pediatric spondylodiscitis is mainly medical, with surgery rarely indicated except for abscess drainage, emergency neurological decompression, or spinal stabilisation [49]. For osteomyelitis of the pubis, early initiation of intravenous antibiotics continued for six weeks carries a high expectation of resolution [5]. Conservative and surgical treatments are safe and effective for patients with lumbosacral tuberculosis [38]. Treatment strategies for periprosthetic joint infection should aim to achieve homeostatic control to prevent symptomatic relapse rather than assuming all infections can be eradicated [43]. Current recommendations support a universal antibiotic prophylaxis protocol rather than an antibiotic regimen individualized to a patient's comorbidities [50].

Operative

Indications: Deterioration in clinical condition or poor response to conservative treatment requires meticulous surgical drainage and excision of both infected and necrotic tissues [1]. Surgical intervention is indicated for polyarticular septic arthritis in immunocompetent adults, a condition often characterized by delayed diagnosis [16]. Successful treatment of granulomatous infection requires potential surgical intervention directed at decompression of neural elements and correction of spinal malalignment [21]. The best treatment for primary pyogenic abscess of the psoas muscle is early operative drainage [46]. Surgical treatment is also required for non-tuberculous mycobacterial infection of the musculoskeletal system [55].

Surgical Approach / Technique: Adequate surgical drainage and débridement are essential for the eradication of musculoskeletal infections due to Bacteroides, as infection sometimes smolders for many years despite intermittent antibiotic treatment [23]. Following debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use [53]. Resolution of systemic symptoms and no signs of recurrent infection at 12-month follow-up were achieved following amputation and olorofim treatment in a patient with Lomentospora prolificans osteomyelitis and septic arthritis despite conventional therapy failure [44].

Adjuncts: Maximizing patient prognosis in orthopedic infections requires adherence to principles of high index of suspicion, correct interpretation of data, thorough surgery, optimization of host factors, and pathogen-specific antibiotic therapy [19]. Expert consultation with infectious disease specialists and clinical microbiologists is recommended for the use of antibiotics for individualized agents [3]. Novel alternative approaches such as phage therapy, antimicrobial peptides, and immunotherapies show promise as adjunct therapies to conventional treatment protocols for improved success rates in septic arthritis management [47].

Other Considerations: Adhering to strict diagnostic and treatment algorithms while utilizing new classifications and scoring systems can predict patient outcomes and improve patient care and resource utilization in pediatric musculoskeletal infections [4]. Pediatric musculoskeletal infections require prompt evaluation and management due to varying clinical presentations and symptoms overlapping with noninfectious diagnoses [8]. Close outpatient follow-up is essential to ensure antibiotic compliance and to identify late consequences of pediatric musculoskeletal infections [7]. For persistent symptoms following AstraZeneca vaccination, infection should be considered, blood tests and imaging performed, and empirical antibiotic administration considered [2]. Early diagnosis, appropriate antimicrobial therapy, and surgical intervention when necessary are crucial for improving patient outcomes in spondylodiscitis [9]. Musculoskeletal infections vary substantially in presentation and required treatment, which is based on the causative organism, the location of the infection, and the age of the patient [11]. The prognosis for complete return of joint function in Hemophilus influenzae septic arthritis is excellent if appropriate therapy is initiated promptly [22]. No definitive recommendation can be made regarding the routine implementation of preoperative S. aureus screening and decolonization protocols because of conflicting literature [54]. Glucocorticoid therapy beyond 6 months and infliximab therapy increased the risk of tuberculosis in patients with spondyloarthritis [51]. Infliximab was found to be safe, effective, and well-tolerated, eliciting satisfactory long-term response and drug survival rates in ankylosing spondylitis patients [13].

Complications

Infection (PJI): The natural history of periprosthetic joint infection (PJI) represents a continuum from initiation to chronicity, with no evidence-based time interval dividing acute from chronic disease [14]. Patients with lower levels of systemic inflammation are likely to present with culture-negative PJI [79]. Risk factors for PJI include prolonged operative times [65], immunocompromised status, corticosteroid therapy, multiple medical comorbidities, prior tuberculosis history, and multiple prior surgeries, particularly for rare mycobacterial infections [62]. While immune status impacts diagnostic accuracy and PJI risk, there are limited prospective analyses and no clinical consensus on the best immunologic markers [6].

Surgical Site Infection (SSI): Gender, rheumatoid arthritis, and long-term corticosteroid use (greater than 1 year) increase SSI risk after shoulder arthroplasty [26]. Systemic lupus erythematosus (SLE) is an independent risk factor for adverse postoperative outcomes, mainly immediate complications, following total hip arthroplasty [64]. Prophylactic amphotericin B therapy is recommended for patients with a history of coccidioidomycosis who are treated with immunosuppressive drugs [84].

Soft Tissue and Necrotizing Infections: Deterioration in clinical condition or poor response to conservative treatment for upper extremity infections following common carp fish handling requires meticulous surgical drainage and excision of infected and necrotic tissues [1]. Vibrio necrotizing fasciitis should be suspected in patients with appropriate clinical findings and a history of contact with seawater or raw seafood [83].

Osteomyelitis: Osteomyelitis of the pubis after strenuous exercise is treated with intravenous antibiotics started early and continued for six weeks, with a high expectation that the infection will resolve [5]. Improvements in radiologic imaging and antibiotic treatment for acute hematogenous osteomyelitis in children have led to earlier detection and decreased morbidity and mortality [15].

Spinal and Joint Infections: When left untreated, spinal infections can cause mechanical instability and possible neurologic compromise [12]. The emergence of methicillin-resistant Staphylococcus aureus as a cause of lumbar facet joint septic arthritis serves as a reminder of the relentless evolutionary progression of this organism [82]. In contrast, the natural history of acute herpetic arthritis is one of spontaneous and rapid resolution without the need for surgical drainage of the joint [17].

Other Considerations: Close outpatient follow-up is essential in pediatric musculoskeletal infections to ensure antibiotic compliance and to identify late consequences of the infection [7]. Infliximab was found to be safe, effective, and well-tolerated in ankylosing spondylitis patients, eliciting satisfactory long-term response and drug survival rates [13]. Psoriatic arthritis is a chronic inflammatory arthropathy that typically follows a moderate course, though up to 47% of cases develop into destructive arthritis [28]. Molecular pathways associated with 'inflamm-aging' and cytokine dysregulation suggest that suppressing pro-inflammatory mechanisms or improving inflammation resolution may delay age-related diseases [24]. Increased inflammatory cytokine levels after intra-articular ankle fracture did not affect functional outcome at 12 months [25].

Recovery

Light activity (weeks): Specific timeframes for light activity are not defined in the current evidence base; however, clinical stability is a prerequisite for progression. Deterioration in clinical condition or poor response to conservative treatment necessitates meticulous surgical drainage and excision of infected and necrotic tissues [1]. For osteomyelitis of the pubis, intravenous antibiotics should be initiated early and continued for six weeks, with a high expectation that the infection will resolve [5]. Adequate surgical drainage and débridement are essential for eradicating musculoskeletal infections caused by Bacteroides, as these infections can smolder for many years despite intermittent antibiotic treatment [23].

Full activity (months): The timeline for full activity is contingent on the specific pathology and the resolution of infection. In acute hematogenous osteomyelitis in children, improvements in radiologic imaging and antibiotic treatment have facilitated earlier detection and decreased morbidity and mortality [15]. Conversely, the natural history of acute herpetic arthritis involves spontaneous and rapid resolution without the need for surgical drainage of the joint [17]. For Hemophilus influenzae septic arthritis, the prognosis for complete return of joint function is excellent if appropriate therapy is initiated promptly [22]. In cases of skeletal tuberculosis treated with streptomycin, patients experience a lowered rate of tuberculous relapse, a lower death rate, a greater chance for survival, and a high rate of functional recovery [66].

Complete recovery / outcome plateau (months): Recovery trajectories vary significantly by etiology. The clinical course of chronic recurrent multifocal osteomyelitis is characterized by slow, continued improvement of symptoms, with a generally good prognosis [97]. In contrast, psoriatic arthritis typically follows a moderate course, though up to 47% of cases progress to destructive arthritis [28]. For patients with ankylosing spondylitis, early anti-inflammatory intervention may slow radiographic progression based on preclinical observations in a mouse model [27], while Infliximab has been found safe, effective, and well-tolerated with satisfactory long-term response and drug survival rates [13]. In the context of periprosthetic joint infection (PJI), there is no evidence-based time interval dividing acute from chronic infection, as the natural history is a continuum from initiation to chronicity [14].

Rehabilitation protocol: Close outpatient follow-up is essential to ensure antibiotic compliance and to identify late consequences of pediatric musculoskeletal infection [7]. For two-stage periprosthetic joint infection treatment, serological and synovial tests cannot be relied on solely to determine the optimal timing of reimplantation; instead, a combination of clinical signs indicating infection resolution, together with declining serological and synovial markers, may be used to guide the timing [99]. In degenerative disc disease, an enhanced local inflammatory response following annular disruption may play a crucial role in pathogenesis, offering potential targets for immune-modulatory therapies to delay progression [98].

Functional milestones: Functional outcomes are influenced by patient-specific factors and the nature of the infection. Gender, rheumatoid arthritis, and long-term (greater than 1 year) corticosteroid use affect surgical site infection risk after shoulder arthroplasty [26]. Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months in a prospective cohort study of 46 patients with ankle fractures [25]. Patients' immune status may impact the diagnostic accuracy and risk of developing periprosthetic joint infection, though there are limited prospective analyses and no clinical consensus on the best immunologic markers [6].

Other Considerations: Long-term structural integrity remains an area requiring further investigation; additional studies with long-term follow-up are needed to determine whether the grafted area in autologous matrix-induced chondrogenesis will maintain structural and functional integrity over time [67]. Furthermore, suppressing pro-inflammatory mechanisms or improving inflammation resolution may delay age-related diseases, while learning from long-lived cohorts could offer insights into healthy aging [24].

Key Evidence

  • [L4] Deterioration in the clinical condition or a poor response to conservative treatment requires a meticulous surgical drainage and excision of both infected and necrotic tissues. (10.1054/jhsb.2001.0660)
  • [L5] The authors recommend considering infection, performing blood tests and imaging, and considering empirical antibiotic administration for persistent symptoms. (10.1016/j.xrrt.2022.04.005)
  • [L5] The authors recommend expert consultation with infectious disease specialists and clinical microbiologists. (10.1016/j.arth.2025.10.100)
  • [L4] Treatment with intravenous antibiotics should be started early and continued for six weeks, with a high expectation that the infection will resolve. (10.2106/00004623-200405000-00027)
  • [L5] Patients' immune status may impact the diagnostic accuracy and risk of developing PJI, but there are limited prospective analyses and no clinical consensus on the best immunologic markers. (10.1016/j.arth.2025.10.097)
  • [L5] Close outpatient follow-up is essential to ensure antibiotic compliance and to identify late consequences of the infection. (10.5435/00124635-200910000-00004)
  • [L4] Early diagnosis, appropriate antimicrobial therapy, and surgical intervention when necessary are crucial for improving patient outcomes. (10.1186/s12891-025-08748-z)
  • [L4] The infection outcome mainly depends on the type of infection and is higher for infective endocarditis. (10.3390/microorganisms11092362)
  • [L5] Musculoskeletal infections are a challenge for surgeons because they vary substantially in their presentation and in their required treatment, which is based on the causative organism, the location of the infection, and the age of the patient. (10.5435/jaaos-d-15-00714)
  • [L3] Infliximab was found to be safe, effective and well-tolerated; it elicited satisfactory long term response and drug survival rates. (10.1186/s12891-015-0620-4)
  • [L5] There is no evidence-based time interval that divides acute from chronic periprosthetic joint infection (PJI); the natural history of infection is a continuum from initiation to chronicity. (10.1016/j.arth.2018.09.069)
  • [L4] Improvements in radiologic imaging and antibiotic treatment have led to earlier detection and decreased morbidity and mortality. (10.5435/00124635-200105000-00003)
  • [Case_report] PASA is a puzzling clinical condition with a frequently delayed diagnosis. (10.1155/2015/602137)
  • [Case_report] The natural history of acute herpetic arthritis is one of spontaneous and rapid resolution without the need for surgical drainage of the joint. (10.2106/00004623-198466040-00023)
  • [L3] Biopsies were more likely to be positive and have characteristic histopathologic features in patients with high CRP and ESR, and prior to start of corticosteroid treatment. (10.1186/s12891-016-1225-2)
  • [L5] The workgroup proposes a universal definition for periprosthetic joint infection (PJI) based on evaluated evidence to standardize diagnosis and facilitate comparison of published evidence. (10.1016/j.arth.2011.09.026)
  • [L5] Successful treatment of a granulomatous infection requires timely diagnosis, prompt medical management, and potential surgical intervention directed at the decompression of neural elements and the correction of spinal malalignment. (10.5435/jaaos-d-13-00213)
  • [L4] The prognosis for complete return of joint function in this infection is excellent if appropriate therapy is initiated promptly. (10.2106/00004623-197456020-00021)
  • [L5] The article discusses molecular pathways associated with 'inflamm-aging' and cytokine dysregulation, suggesting that suppressing pro-inflammatory mechanisms or improving inflammation resolution may delay age-related diseases, while learning from long-lived cohorts could offer insights into healthy aging. (10.3389/fimmu.2018.00586)
  • [L3] Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months. (10.1186/s13018-021-02473-8)
  • [L3] Gender, rheumatoid arthritis, and long-term (>1 year) corticosteroid use affect SSI risk after shoulder arthroplasty. (10.1016/j.jse.2017.04.006)
  • [Paper] This preclinical observation suggests that early anti-inflammatory intervention may slow radiographic progression in AS patients. (10.1186/s12891-017-1600-7)
  • [L5] Psoriatic arthritis is a chronic inflammatory arthropathy that typically follows a moderate course, though up to 47% of cases develop into destructive arthritis. (10.5435/jaaos-20-01-028)
  • [L3] It is important to develop and maintain a clinical suspicion for K. kingae infection in young patients presenting atypically, and routine PCR testing is recommended. (10.1302/0301-620x.103b3.bjj-2020-0800.r1)
  • [L5] Intraoperative findings, including sinus tracts, cell counts, frozen sections, and point-of-care diagnostic tests, must be communicated to infectious disease specialists to guide diagnosis and management. (10.1016/j.arth.2018.09.075)
  • [Case_report] Pathologic examination should be performed as well as culture tests to detect and identify the bacteria accurately, as the probability for culture confirmation is quite low. (10.1186/s12891-019-2576-2)
  • [L4] CRP and ESR are the most commonly accepted screening tests with high sensitivity, while combining serological tests improves diagnostic accuracy but requires further work to identify the optimal combination; diagnosis of PJI cannot be based solely on serological tests at this time. (10.1016/j.arth.2018.09.070)
  • [Case_report] The case highlights the importance of obtaining cultures for unusual pathogens and using susceptibility testing to guide antimicrobial therapy in immunosuppressed patients. (10.1007/s11552-008-9138-7)
  • [L5] P acnes should be considered as a causative organism in bone and joint infection, particularly when the clinical picture is indolent and traditional diagnostic testing is negative. (10.1016/j.jse.2011.02.016)
  • [L4] Early diagnosis allows for appropriate treatment modification, as pyrazinamide is ineffective against BCG. (10.2106/00004623-199909000-00012)
  • [L3] All available imaging modalities, including conventional imaging such as plain radiography, CT, MRI, and WBC scintigraphy, have limited accuracy and should not be used as standalone tests to identify osteomyelitis. (10.1016/j.arth.2025.10.083)
  • [L4] Conservative and surgical treatments are safe and effective and produce good clinical outcomes for patients with lumbosacral tuberculosis. (10.1371/journal.pone.0130185)
  • [L3] Due to multifocal spondylodiscitis being found in approximately 13% of cases, MRI imaging of the total spine is recommended to avoid overlooking additional infection levels, which can impact the therapeutic strategy chosen. (10.1186/s12891-020-03928-5)
  • [L4] Imaging methods including computed tomography, magnetic resonance imaging, and nuclear medicine techniques have the potential to demonstrate the extent of soft-tissue and bone involvement in patients with periprosthetic joint infection and may help guide bone resection. (10.1016/j.arth.2018.09.073)
  • [L5] Early use of MRI helps delineate the extent of infection, aids in the consideration of surgery, and provides valuable information for surgical planning. (10.5435/jaaos-23-01-29)
  • [L5] Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in immunocompromised patients, and historically outcomes have been poor due to a lack of evidence-based treatment guidelines. (10.5435/jaaos-22-06-390)
  • [L4] Treatment strategies should aim to achieve homeostatic control to prevent symptomatic relapse rather than assuming all infections can be eradicated, challenging the false dichotomy of infection eradication versus recurrence. (10.1016/j.arth.2025.10.033)
  • [L5] Despite conventional therapy failure, the patient achieved resolution of systemic symptoms and no signs of recurrent infection at 12-month follow-up following amputation and olorofim treatment. (10.1016/j.xrrt.2026.100698)
  • [L5] The optimal timing for reimplantation has not been established and should be based on clinical control of infection. (10.1016/j.arth.2018.09.028)
  • [L4] The best treatment is early operative drainage and administration of systemic antibiotics. (10.2106/00004623-199305000-00021)
  • [L4] The review highlights that novel alternative approaches such as phage therapy, antimicrobial peptides, and immunotherapies show promise as adjunct therapies to conventional treatment protocols for improved success rates in septic arthritis management. (10.1186/s12891-021-04383-6)
  • [L5] Most patients with spondylodiscitis are successfully treated by conservative means; however, surgical treatment is indicated for doubtful diagnosis, progressive neurological deficits, progressive spinal deformity, failure to respond to treatment, and unresolved pain. (10.1302/2058-5241.2.160062)
  • [L4] Treatment is mainly medical, with surgery rarely indicated except for abscess drainage, emergency neurological decompression, or spinal stabilisation. (10.1530/eor-2025-0224)
  • [L2] The results of the present study support the current recommendations of a universal antibiotic prophylaxis protocol rather than an antibiotic regimen individualized to a patient's comorbidities. (10.1016/j.arth.2016.11.021)
  • [L3] Glucocorticoid therapy beyond 6 months and infliximab therapy increased the risk of TB. (10.1186/s12891-020-03855-5)
  • [L4] Radiographic findings in chronic osteomyelitis were universally observed in all patients, demonstrating a high degree of concordance among specialists, with the exception of soft tissue swelling. (10.1186/s12891-023-07121-2)
  • [L3] After debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use. (10.1186/s12891-020-03214-4)
  • [L4] No definitive recommendation can be made regarding the routine implementation of preoperative S. aureus screening and decolonization protocols because of conflicting literature. (10.1016/j.arth.2018.09.053)
  • [L4] Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes. (10.1302/0301-620x.96b11.33427)
  • [L4] We recommend an MRI scan of the whole spine and pelvis in patients with MSSA septicaemia with back pain, when the primary source of infection has not been identified or clinical examination is unreliable. (10.1302/0301-620x.99b11.bjj-2016-1093.r1)
  • [L4] The authors suggest that future cases may require surgical intervention for removal of infected tissue and fusion, even without abscess. (10.2106/00004623-197355070-00008)
  • [L1] The diagnostic effect of this nuclear imaging method for pyogenic spondylitis without previous spine surgery seems to be better than that for the postoperative ones. (10.1186/s13018-023-03507-z)
  • [Case_report] Pyomyositis should be considered in any HIV-positive patient presenting with painful and swollen muscles; CT-guided aspiration and antibiotic therapy are effective treatments. (10.2106/00004623-199304000-00013)
  • [Paper] The workgroup proposes a new definition for periprosthetic joint infection (PJI) to serve as a 'gold standard' that can be universally adopted by clinicians, surveillance authorities, and researchers to ensure consistency in diagnosis and management. (10.1007/s11999-011-2102-9)
  • [Case_report] Physicians and radiologists should consider gouty spondylitis when encountering such conditions by combining imaging with patient history and clinical manifestations. (10.1186/s12891-019-2813-8)
  • [L4] Mycobacterial infections in periprosthetic joint infection are rare, with risk factors including immunocompromised status, corticosteroid therapy, multiple medical comorbidities, prior tuberculosis history, and multiple prior surgeries. (10.1016/j.arth.2025.08.037)
  • [L2] Fluorine-18 fluorodeoxyglucose-positron emission tomography is highly accurate as a single technique for the evaluation of chronic musculoskeletal infections and is especially valuable in the evaluation of the central skeleton. (10.2106/00004623-200105000-00002)
  • [L3] SLE is an independent risk factor for adverse postoperative outcomes, mainly immediate complications, but the long-term outcome is good enough to offer surgical treatment that will improve quality of life. (10.1016/j.arth.2017.06.021)
  • [L1] There is a moderate level of evidence supporting an association between prolonged operative times and increased risks of SSIs/PJIs. (10.1016/j.arth.2018.09.064)
  • [L4] The study reflects a lowered rate of tuberculous relapse, a lower death rate from tuberculosis, a greater chance for survival, and a high rate of functional recovery. (10.2106/00004623-195840050-00024)
  • [L4] However, further studies with long-term follow-up are needed to determine whether the grafted area will maintain structural and functional integrity over time. (10.1007/s00167-010-1042-3)
  • [Paper] The proceedings summarize the discussions and recommendations from the International Consensus Meeting on Periprosthetic Joint Infection, aiming to standardize definitions, diagnosis, and treatment approaches for PJI. (10.1016/j.arth.2013.09.024)
  • [L4] While validated for chronic PJI in both hips and knees, the criteria require further validation for acute infections and novel microbiological methods. (10.1016/j.arth.2018.09.045)
  • [L4] Poor evidence suggests that COVID-19 could target the musculoskeletal system causing reactive arthritis at its post infectious stage. (10.1186/s13018-023-03651-6)
  • [L3] Structural change of the spine was associated with MetS in PsA. (10.1186/s12891-021-04222-8)
  • [L5] The PPS injury produces alterations in GH kinematics with implications for GH joint instability, increased GH joint loading, and potential joint damage. (10.1016/j.jse.2024.12.023)
  • [L3] This procedure can improve patients' pain, neurological function and kyphotic deformity and achieve effects similar to traditional methods, making it an ideal surgical treatment for thoracolumbar fractures in AS patients. (10.1186/s13018-022-03378-w)
  • [L3] Our findings indicate that using a combination of IDEAL and T2 mapping may provide deeper insights into the pathophysiological degeneration of paraspinal muscles in AS. (10.1186/s12891-022-05570-9)
  • [L3] The results suggest that PJI cases with lower levels of systemic inflammation are likely to be culture-negative. (10.1186/s13018-021-02450-1)
  • [L4] Modic changes, particularly Type 2, are common radiological findings in lumbar spine imaging, most frequently occurring at L4/L5 and L5/S1 levels. (10.1186/s12891-025-09182-x)
  • [L5] This review provides an overview of the current status of miRNA research in degenerative disc pathology, focusing on the involvement of miRNAs in ECM degradation, apoptosis, inflammation, and mechanobiology. (10.3390/ijms21103601)
  • [L4] The emergence of methicillin-resistant Staphylococcus aureus as a cause of facet joint septic arthritis serves as a stark reminder of the relentless evolutionary progression of this organism. (10.2106/jbjs.h.01888)
  • [L4] The diagnosis of Vibrio necrotizing fasciitis should be suspected in patients with appropriate clinical findings and a history of contact with seawater or raw seafood. (10.2106/00004623-200411000-00021)
  • [L4] Prophylactic amphotericin B therapy is recommended for patients with a history of coccidioidomycosis who are treated with immunosuppressive drugs. (10.2106/00004623-197355020-00024)
  • [L4] Preoperative planning to accurately select and insert pedicle screws in adolescent idiopathic scoliosis should be based on anatomical limitations in the apical vertebra region, apical vertebra level, and apical vertebral rotation degree. (10.1186/s12891-022-05799-4)
  • [L5] The results from this study suggested that relatively low magnitude tensile stress might play an essential role in the anti-inflammatory process and the relief of low-back pain (LBP). (10.1186/s13018-015-0159-y)
  • [L2] Overall bone metabolism of the operated intervertebral disc space at six weeks had the highest diagnostic accuracy for predicting the fusion status at one year. (10.1186/s13018-025-05814-z)
  • [L4] If the diagnosis and treatment are delayed, spinal damage and other consequences might be incurable. (10.1186/s12891-021-04426-y)
  • [L4] GK is significantly associated with functional status, spinal mobility and QoL in AS patients. (10.1186/s12891-017-1711-1)
  • [L4] Therefore, there is no need for additional training to improve postural control in these adolescents with idiopathic scoliosis. (10.1186/s12891-024-08210-6)
  • [L5] Diffuse idiopathic skeletal hyperostosis (DISH) is a common disorder of unknown etiology characterized by back pain, spinal stiffness, and flowing ossification along the anterolateral margins of at least four contiguous vertebrae. (10.5435/00124635-200107000-00006)
  • [L5] Serious cervical spine injuries in football have not been eliminated, though rates have declined since the outlawing of spearing; continued education on risk minimization is necessary. (10.1177/0363546506290796)
  • [Case_report] The clinical course is one of slow, continued improvement of the symptoms, and the prognosis is good. (10.2106/00004623-198466070-00022)
  • [L4] This enhanced local inflammatory response may play a crucial role in the pathogenesis and progression of IDD, offering potential targets for immune-modulatory therapies to delay IDD progression. (10.1186/s12891-025-09340-1)
  • [L2] Serological and synovial tests cannot be relied on solely to determine the optimal timing of reimplantation; a combination of clinical signs indicating infection resolution, together with declining serological and synovial markers, may be used to guide the timing. (10.1016/j.arth.2025.10.095)

See Also

References

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[2] Local myofascitis of the deltoid muscle after administration of the AstraZeneca (AZD1222) COVID-19 vaccine: two cases, infectious and inflammatory. JSES Reviews, Reports, and Techniques. 2022. DOI: 10.1016/j.xrrt.2022.04.005

[3] 2025 ICM: Use of Antibiotics for Individualized Agents. The Journal of Arthroplasty. 2025. DOI: 10.1016/j.arth.2025.10.100

[4] Chapter 64 Pediatric Musculoskeletal Infections, Inflammatory Disorders, and Nonaccidental Trauma. 2020.

[5] Osteomyelitis of the Pubis After Strenuous Exercise. The Journal of Bone & Joint Surgery. 2004. DOI: 10.2106/00004623-200405000-00027

[6] 2025 ICM: Immune Status. The Journal of Arthroplasty. 2025. DOI: 10.1016/j.arth.2025.10.097

[7] Pediatric Musculoskeletal Infection: Trends and Antibiotic Recommendations. Journal of the American Academy of Orthopaedic Surgeons. 2009. DOI: 10.5435/00124635-200910000-00004

[8] Chapter 132 Musculoskeletal Infection of Children and Adolescents. 2019.

[9] Clinical and microbiological profile of spondylodiscitis: a retrospective analysis. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08748-z

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[11] Update in Pediatric Musculoskeletal Infections: When It Is, When It Isn't, and What to Do. Journal of the American Academy of Orthopaedic Surgeons. 2016. DOI: 10.5435/jaaos-d-15-00714

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[35] Propionibacterium acnes infection of the elbow. Journal of Shoulder and Elbow Surgery. 2011. DOI: 10.1016/j.jse.2011.02.016

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[43] Emerging Concepts in Periprosthetic Joint Infection Research: Infection Recurrence and Microbe Persistence. The Journal of Arthroplasty. 2025. DOI: 10.1016/j.arth.2025.10.033

[44] Lomentospora prolificans osteomyelitis and septic arthritis in an immunocompromised patient, requiring transhumeral amputation and use of the novel antifungal olorofim. JSES Reviews, Reports, and Techniques. 2026. DOI: 10.1016/j.xrrt.2026.100698

[45] Hip and Knee Section, Treatment, Two-Stage Exchange: Proceedings of International Consensus on Orthopedic Infections. The Journal of Arthroplasty. 2019. DOI: 10.1016/j.arth.2018.09.028

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[47] Novel therapeutic interventions towards improved management of septic arthritis. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04383-6

[48] Spondylodiscitis revisited. EFORT Open Reviews. 2017. DOI: 10.1302/2058-5241.2.160062

[49] A narrative review of our developing knowledge about paediatric spondylodiscitis based on existing literature. EFORT Open Reviews. 2026. DOI: 10.1530/eor-2025-0224

[50] Should Preoperative Antibiotics Be Tailored According to Patient's Comorbidities and Susceptibility to Organisms?. The Journal of Arthroplasty. 2017. DOI: 10.1016/j.arth.2016.11.021

[51] Risk of tuberculosis in patients with spondyloarthritis: data from a centralized electronic database in Hong Kong. BMC Musculoskeletal Disorders. 2020. DOI: 10.1186/s12891-020-03855-5

[52] Prevalence of radiographic findings in chronic osteomyelitis. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-023-07121-2

[53] Antibiotic treatment regimens for bone infection after debridement: a study of 902 cases. BMC Musculoskeletal Disorders. 2020. DOI: 10.1186/s12891-020-03214-4

[54] General Assembly, Prevention, Risk Mitigation, Local Factors: Proceedings of International Consensus on Orthopedic Infections. The Journal of Arthroplasty. 2019. DOI: 10.1016/j.arth.2018.09.053

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[56] The orthopaedic manifestation and outcomes of methicillin-sensitive Staphylococcus aureus septicaemia. The Bone & Joint Journal. 2017. DOI: 10.1302/0301-620x.99b11.bjj-2016-1093.r1

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[62] 2025 ICM: Mycobacterium. The Journal of Arthroplasty. 2025. DOI: 10.1016/j.arth.2025.08.037

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[64] Total Hip Arthroplasty Outcomes: An 18-Year Experience in a Single Center: Is Systemic Lupus Erythematosus a Potential Risk Factor for Adverse Outcomes?. The Journal of Arthroplasty. 2017. DOI: 10.1016/j.arth.2017.06.021

[65] General Assembly, Prevention, Operating Room - Surgical Technique: Proceedings of International Consensus on Orthopedic Infections. The Journal of Arthroplasty. 2019. DOI: 10.1016/j.arth.2018.09.064

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[73] Association between syndesmophyte and metabolic syndrome in patients with psoriatic arthritis or ankylosing spondylitis: a cross-sectional study. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04222-8

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[87] Low magnitude of tensile stress represses the inflammatory response at intervertebral disc in rats. Journal of Orthopaedic Surgery and Research. 2015. DOI: 10.1186/s13018-015-0159-y

[88] 18F-fluoride PET/CT as an early predictor of bony fusion after posterior lumbar interbody fusion– a prospective study. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05814-z

[89] Evaluation of patients admitted with musculoskeletal tuberculosis: sixteen years’ experience from a single center in Turkey. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04426-y

[90] Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis: a retrospective case series study. BMC Musculoskeletal Disorders. 2017. DOI: 10.1186/s12891-017-1711-1

[91] Do adolescents with different types and degrees of idiopathic scoliosis curves differ in postural control compared to their healthy peers? a cross-sectional study. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-08210-6

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[99] 2025 ICM: Two-Stage. The Journal of Arthroplasty. 2025. DOI: 10.1016/j.arth.2025.10.095

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a. reproduce and Share the Licensed Material, in whole or in part, for NonCommercial purposes only; and

b. produce, reproduce, and Share Adapted Material for NonCommercial purposes only.

2. Exceptions and Limitations. For the avoidance of doubt, where Exceptions and Limitations apply to Your use, this Public License does not apply, and You do not need to comply with its terms and conditions.

3. Term. The term of this Public License is specified in Section 6(a).

4. Media and formats; technical modifications allowed. The Licensor authorizes You to exercise the Licensed Rights in all media and formats whether now known or hereafter created, and to make technical modifications necessary to do so. The Licensor waives and/or agrees not to assert any right or authority to forbid You from making technical modifications necessary to exercise the Licensed Rights, including technical modifications necessary to circumvent Effective Technological Measures. For purposes of this Public License, simply making modifications authorized by this Section 2(a) (4) never produces Adapted Material.

5. Downstream recipients.

a. Offer from the Licensor -- Licensed Material. Every recipient of the Licensed Material automatically receives an offer from the Licensor to exercise the Licensed Rights under the terms and conditions of this Public License.

b. No downstream restrictions. You may not offer or impose any additional or different terms or conditions on, or apply any Effective Technological Measures to, the Licensed Material if doing so restricts exercise of the Licensed Rights by any recipient of the Licensed Material.

6. No endorsement. Nothing in this Public License constitutes or may be construed as permission to assert or imply that You are, or that Your use of the Licensed Material is, connected with, or sponsored, endorsed, or granted official status by, the Licensor or others designated to receive attribution as provided in Section 3(a)(1)(A)(i).

b. Other rights.

1. Moral rights, such as the right of integrity, are not licensed under this Public License, nor are publicity, privacy, and/or other similar personality rights; however, to the extent possible, the Licensor waives and/or agrees not to assert any such rights held by the Licensor to the limited extent necessary to allow You to exercise the Licensed Rights, but not otherwise.

2. Patent and trademark rights are not licensed under this Public License.

3. To the extent possible, the Licensor waives any right to collect royalties from You for the exercise of the Licensed Rights, whether directly or through a collecting society under any voluntary or waivable statutory or compulsory licensing scheme. In all other cases the Licensor expressly reserves any right to collect such royalties, including when the Licensed Material is used other than for NonCommercial purposes.

Section 3 -- License Conditions.

Your exercise of the Licensed Rights is expressly made subject to the following conditions.

a. Attribution.

1. If You Share the Licensed Material (including in modified form), You must:

a. retain the following if it is supplied by the Licensor with the Licensed Material:

i. identification of the creator(s) of the Licensed Material and any others designated to receive attribution, in any reasonable manner requested by the Licensor (including by pseudonym if designated);

ii. a copyright notice;

iii. a notice that refers to this Public License;

iv. a notice that refers to the disclaimer of warranties;

v. a URI or hyperlink to the Licensed Material to the extent reasonably practicable;

b. indicate if You modified the Licensed Material and retain an indication of any previous modifications; and

c. indicate the Licensed Material is licensed under this Public License, and include the text of, or the URI or hyperlink to, this Public License.

2. You may satisfy the conditions in Section 3(a)(1) in any reasonable manner based on the medium, means, and context in which You Share the Licensed Material. For example, it may be reasonable to satisfy the conditions by providing a URI or hyperlink to a resource that includes the required information.

3. If requested by the Licensor, You must remove any of the information required by Section 3(a)(1)(A) to the extent reasonably practicable.

4. If You Share Adapted Material You produce, the Adapter's License You apply must not prevent recipients of the Adapted Material from complying with this Public License.

Section 4 -- Sui Generis Database Rights.

Where the Licensed Rights include Sui Generis Database Rights that apply to Your use of the Licensed Material:

a. for the avoidance of doubt, Section 2(a)(1) grants You the right to extract, reuse, reproduce, and Share all or a substantial portion of the contents of the database for NonCommercial purposes only;

b. if You include all or a substantial portion of the database contents in a database in which You have Sui Generis Database Rights, then the database in which You have Sui Generis Database Rights (but not its individual contents) is Adapted Material; and

c. You must comply with the conditions in Section 3(a) if You Share all or a substantial portion of the contents of the database.

For the avoidance of doubt, this Section 4 supplements and does not replace Your obligations under this Public License where the Licensed Rights include other Copyright and Similar Rights.

Section 5 -- Disclaimer of Warranties and Limitation of Liability.

a. UNLESS OTHERWISE SEPARATELY UNDERTAKEN BY THE LICENSOR, TO THE EXTENT POSSIBLE, THE LICENSOR OFFERS THE LICENSED MATERIAL AS-IS AND AS-AVAILABLE, AND MAKES NO REPRESENTATIONS OR WARRANTIES OF ANY KIND CONCERNING THE LICENSED MATERIAL, WHETHER EXPRESS, IMPLIED, STATUTORY, OR OTHER. THIS INCLUDES, WITHOUT LIMITATION, WARRANTIES OF TITLE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, ABSENCE OF LATENT OR OTHER DEFECTS, ACCURACY, OR THE PRESENCE OR ABSENCE OF ERRORS, WHETHER OR NOT KNOWN OR DISCOVERABLE. WHERE DISCLAIMERS OF WARRANTIES ARE NOT ALLOWED IN FULL OR IN PART, THIS DISCLAIMER MAY NOT APPLY TO YOU.

b. TO THE EXTENT POSSIBLE, IN NO EVENT WILL THE LICENSOR BE LIABLE TO YOU ON ANY LEGAL THEORY (INCLUDING, WITHOUT LIMITATION, NEGLIGENCE) OR OTHERWISE FOR ANY DIRECT, SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL, PUNITIVE, EXEMPLARY, OR OTHER LOSSES, COSTS, EXPENSES, OR DAMAGES ARISING OUT OF THIS PUBLIC LICENSE OR USE OF THE LICENSED MATERIAL, EVEN IF THE LICENSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH LOSSES, COSTS, EXPENSES, OR DAMAGES. WHERE A LIMITATION OF LIABILITY IS NOT ALLOWED IN FULL OR IN PART, THIS LIMITATION MAY NOT APPLY TO YOU.

c. The disclaimer of warranties and limitation of liability provided above shall be interpreted in a manner that, to the extent possible, most closely approximates an absolute disclaimer and waiver of all liability.

Section 6 -- Term and Termination.

a. This Public License applies for the term of the Copyright and Similar Rights licensed here. However, if You fail to comply with this Public License, then Your rights under this Public License terminate automatically.

b. Where Your right to use the Licensed Material has terminated under Section 6(a), it reinstates:

1. automatically as of the date the violation is cured, provided it is cured within 30 days of Your discovery of the violation; or

2. upon express reinstatement by the Licensor.

For the avoidance of doubt, this Section 6(b) does not affect any right the Licensor may have to seek remedies for Your violations of this Public License.

c. For the avoidance of doubt, the Licensor may also offer the Licensed Material under separate terms or conditions or stop distributing the Licensed Material at any time; however, doing so will not terminate this Public License.

d. Sections 1, 5, 6, 7, and 8 survive termination of this Public License.

Section 7 -- Other Terms and Conditions.

a. The Licensor shall not be bound by any additional or different terms or conditions communicated by You unless expressly agreed.

b. Any arrangements, understandings, or agreements regarding the Licensed Material not stated herein are separate from and independent of the terms and conditions of this Public License.

Section 8 -- Interpretation.

a. For the avoidance of doubt, this Public License does not, and shall not be interpreted to, reduce, limit, restrict, or impose conditions on any use of the Licensed Material that could lawfully be made without permission under this Public License.

b. To the extent possible, if any provision of this Public License is deemed unenforceable, it shall be automatically reformed to the minimum extent necessary to make it enforceable. If the provision cannot be reformed, it shall be severed from this Public License without affecting the enforceability of the remaining terms and conditions.

c. No term or condition of this Public License will be waived and no failure to comply consented to unless expressly agreed to by the Licensor.

d. Nothing in this Public License constitutes or may be interpreted as a limitation upon, or waiver of, any privileges and immunities that apply to the Licensor or You, including from the legal processes of any jurisdiction or authority.

Creative Commons is not a party to its public licenses. Notwithstanding, Creative Commons may elect to apply one of its public licenses to material it publishes and in those instances will be considered the “Licensor.” The text of the Creative Commons public licenses is dedicated to the public domain under the CC0 Public Domain Dedication. Except for the limited purpose of indicating that material is shared under a Creative Commons public license or as otherwise permitted by the Creative Commons policies published at creativecommons.org/policies, Creative Commons does not authorize the use of the trademark "Creative Commons" or any other trademark or logo of Creative Commons without its prior written consent including, without limitation, in connection with any unauthorized modifications to any of its public licenses or any other arrangements, understandings, or agreements concerning use of licensed material. For the avoidance of doubt, this paragraph does not form part of the public licenses.

Creative Commons may be contacted at creativecommons.org.