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.

Paediatric pustulotic arthro-osteitis patient with an IL36RN variant, heterozygous c.115+6T>C, who was successfully treated with tonsillectomy: A case report and literature review.

Pustulotic arthro-osteitis (PAO) is an infrequent condition, with its manifestation in children being even rare. Some reports propose an association between genetic variants and the onset of PAO. Currently, no definitive treatment protocol exists for paediatric patients with PAO. In this study, we present the paediatric case of PAO with an IL36RN variant who was successfully treated with tonsillectomy.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Unravelling a hidden pathology of a vertebral fracture in a teenage girl.

BACKGROUND: Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease "osteitis fibrosa cystica" is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. CASE PRESENTATION: A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. CONCLUSION: In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition.

Diagnostic features of osteitis condensans ilii by MRI-a systematic literature review.

OBJECTIVE: To describe and evaluate the current knowledge of MRI characteristics of osteitis condensans ilii (OCI) in the diagnostics and differentiation of OCI from other conditions. MATERIALS AND METHODS: The databases PubMed, EMBASE, Scopus, and Web of Science were searched from their inception to March 2024 using the search terms "Magnetic Resonance Imaging" (MESH term in PubMed) and "osteitis condensans ilii" and limited to English language. Two reviewers independently screened titles, abstracts, and full-text eligibility and assessed the risk of bias according to Quality Assessment of Diagnostic Accuracy Studies, QUADAS-2. RESULTS: The search identified 53 records. Case reports, letters/notes, and conference abstracts were excluded, resulting in 24 reports assessed by full-text, 9 research articles, 14 reviews, and a book chapter. Five retrospective research studies were found eligible for the review. Detailed MRI features of OCI were only described in two studies of patients with pain where they encompassed manifest subchondral iliac sclerosis often accompanied by bone marrow edema (BME) located peripheral to the sclerosis and displaying a continuous distribution and frequently accompanied by sacral BME. Erosions were rare and ankylosis did not occur. Fat deposition in the bone marrow was frequent and similar to BME often located to anterior strain-related joint areas. The QUADAS-2 assessments revealed risks of bias in all studies analyzed, especially regarding general applicability of the MRI features. CONCLUSION: There is a lack of valid data describing characteristic MRI features in general groups of OCI patients with and without pain.

The effects of chlorhexidine gel and tranexamic acid application after tooth extraction on the risk of alveolar osteitis formation: a double blind clinical study.

BACKGROUND: Alveolar osteitis(AO), one of the most common complications occurring in 1-10% of cases following tooth extraction, occurs due to the disruption of clot formation in the extraction socket. This study aims to evaluate the effect of using absorbable gelatin sponge, chlorhexidine gel, and tranexamic acid agents on the development of AO following extraction. METHODS: Between March and October 2023, the teeth of 98 healthy patients (average age: 38, range: 19-62) with extraction indications were extracted at Recep Tayyip Erdogan University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery. 113 extraction sockets(85 molars and 28 premolars) were randomly treated with absorbable gelatin sponge(AGS), chlorhexidine gel with AGS, and tranexamic acid with AGS. Pain and edema levels were recorded using visual analog scale(VAS) ranging from 0 to 10 by the patients. Additionally, presence of halitosis, trismus and exposed bone was noted on forms on 3rd and 7th days (recorded as present or absent). The study prospectively aimed to prevent AO using 3 different dental agents in the extraction sockets. Statistical analyses of the study were conducted using the SPSS software package. RESULTS: Alveolitis was observed in 12 out of 113 tooth extractions(%10.6). Pain and edema scores significantly decreased in absorbable gelatin sponge group on the 7th day (p < 0.05). Pain score on the 7th day in chlorhexidine group and age, edema score on the 7th day in tranexamic acid group, were found to be significantly higher (p < 0.05). CONCLUSION: Incidence of AO, can be reduced by placing agents in the extraction socket, preventing post-extraction pain experienced by patients. CLINICAL TRIALS ID: NCT06435832.

Oral manifestations in women using hormonal contraceptive methods: a systematic review.

OBJECTIVES: To investigate the oral manifestations in women of reproductive age using hormonal contraceptive methods. MATERIALS AND METHODS: This review is based on the PRISMA statement. A literature search incorporated observational studies from the last 21 years. An investigative question was formulated using the PICO model, studies were selected, and a quality analysis was performed using the modified STROBE guidelines. A bibliometric analysis was performed, and the data were examined. RESULTS: Thirteen articles were included, with the majority evaluating periodontal status. Others analyzed factors such as the presence of alveolar osteitis, oral candidiasis, and salivary microbiome dysbiosis. Ten articles were deemed to have a low risk of bias. CONCLUSIONS: Hormonal contraceptives may increase the risk of alveolar osteitis following tooth extraction and increase the presence of the Candida species in the oral cavity. They also affect the periodontium, such as the frequent development of gingivitis, but do not lead to changes in the salivary microbiome. CLINICAL RELEVANCE: The increasing number of women using hormonal contraceptives and the knowledge that these contraceptives can produce oral cavity alterations underscore the need to evaluate the oral manifestations found in these women.

The Use of Platelet-Rich Fibrin (PRF) in the Management of Dry Socket: A Systematic Review.

Dry socket or alveolar osteitis is a common postoperative complication following tooth extraction, characterized by severe pain due to the disintegration of the blood clot within the socket. Various factors contribute to its development, such as traumatic extraction, patient age and sex, smoking, and anesthetic use. To mitigate this condition, socket preservation techniques, including the use of bone substitute materials, have been employed. Platelet-rich fibrin (PRF) has emerged as a promising biomaterial, enhancing healing and reducing the incidence of dry socket. Materials and Methods: This systematic review, adhering to the PRISMA guidelines and registered with PROSPERO (ID: CRD 578018), examines the efficacy of PRF in managing dry socket by analyzing studies from PubMed, Scopus, and Web of Science published between January 2013 and May 2024. Boolean keywords have been used in the search strategy: ("Treatment") AND ("Dry Socket") AND ("Platelet Rich Fibrin" OR "PRF"). A total of 738 publications were found using the electronic database search. After the screening phase, 13 records were chosen for qualitative analysis. The results from multiple clinical trials and comparative studies indicate that PRF significantly reduces postoperative pain, expedites healing, and lowers the incidence of Alveolar Osteitis. Despite promising results, further large-scale, randomized studies are needed to validate PRF as a standard treatment for dry socket.

Investigation of alveolar osteitis and the effectiveness of laser treatment: a unified Meta-analysis and review of the literature.

BACKGROUND: Post-tooth extraction, dry socket is a frequently encountered complication, causing substantial pain and hindering the healing process. Conventional approaches to manage this condition have traditionally involved the use of antiseptic dressings to diminish bacterial presence and facilitate healing. This study aims to assess the efficacy of laser therapy in the symptomatic treatment of alveolitis. METHODS: A literature search was conducted on PubMed, Embase, Scopus, Google Scholar, Web of Science, focusing on publications from 1998 to 31/01/2024 using relevant keywords. The combination of "laser" and "dry socket" was executed through the boolean connection AND. RESULTS: At the conclusion of the study, a total of 50 studies were identified across the three search engines, with only three selected for the current systematic study and meta-analysis. The meta-analysis indicated that laser treatment proves effective in addressing alveolitis compared to Alvogyl. However, the correlation between the two was not highly significant. CONCLUSION: These findings suggest that laser therapy may serve as a viable alternative to traditional treatments for dry socket. This minimally invasive procedure has the potential to alleviate pain and promote healing with fewer associated side effects."

Modified pustulotic arthro-osteitis diagnostic guidance 2022 - Modified Sonozaki criteria - Secondary publication.

The concept of pustulotic arthro-osteitis (PAO) was first reported by Sonozaki et al. in 1979, with diagnostic criteria (Sonozaki criteria) proposed in 1981. These criteria have served as the gold standard for PAO diagnosis for over 40 years. In recent years, there has been an increasing emphasis on maximizing the quality of life of patients with PAO. This is achieved by striving for clinical remission, structural remission, and functional remission through early diagnosis and appropriate therapeutic intervention from an early stage. This article is an English translation of a summary of the 'Modified PAO Diagnostic Guidance 2022', edited by the Japan Ministry of Health, Labour and Welfare's Research Group on improvement of medical standard and quality of life of patients with spondyloarthritis and related diseases represented by ankylosing spondylitis and the Japan Spondyloarthritis Society. This guidance is intended to be helpful to both Japanese and global communities in rheumatology and spondyloarthritis.

Clinical and therapeutic diversity in adult chronic nonbacterial osteomyelitis (CNO) of the sternocostoclavicular region: a meta-analysis.

OBJECTIVES: Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus. METHODS: Systematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI. RESULTS: Forty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively. CONCLUSION: CNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH.

Utility of nailfold capillary assessment for predicting pustulotic arthro-osteitis in palmoplantar pustulosis based on a prospective cohort study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known. OBJECTIVE: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP. METHODS: We conducted a prospective cohort study in a population of 102 PPP patients. Correlations of NFC abnormalities, including nailfold bleeding and enlarged capillaries, with the prevalence of PAO, the incidence of new PAO, and serum levels of cytokines were analyzed. RESULTS: Detailed examination revealed that of 102 PPP patients, 52 without PAO and 50 with PAO. Both nailfold bleeding and enlarged capillaries were significantly more frequent in patients with PAO (50.0% vs 92.0%, P < .0001; 50.0% vs 94.0%, P < .0001). In addition, PPP patients without PAO were prospectively observed before they developed PAO (mean 28 months [1-52 months]). Multivariate analysis suggested that these NFC abnormalities were predictors of PAO development (hazard ratio 3.37, 95% confidence interval 1.13-10.07; 3.37, 1.13-10.07) and guselkumab prevent PAO development (0.093, 0.012-0.76). The degree of NFC abnormalities correlated with the severity of PAO and serum cytokine levels. LIMITATIONS: All participants were Japanese. CONCLUSION: NFC abnormalities could be predictors of PAO in PPP patients, and their degree indicators of disease severity.

Variable Bone Phenotypes in Patients with Pseudohypoparathyroidism.

PURPOSE OF REVIEW: Pseudohypoparathyroidism (PHP) is a disorder caused by mutations and/or epigenetic changes at the complex GNAS locus. It is characterized by hypocalcemia, hyperphosphatemia, and an elevated parathyroid hormone concentration secondary to the resistance of target tissues to the biological actions of parathyroid hormone. PHP is divided into several subtypes with different yet overlapping phenotypes. Research on the bone status in patients with PHP is sparse and has yielded inconsistent results. This review was performed to summarize the current knowledge on the bone phenotypes and possible mechanisms of PHP. RECENT FINDINGS: Patients with PHP exhibit highly variable bone phenotypes and increased concentrations of bone turnover markers. Long-standing elevation of the parathyroid hormone concentration may lead to hyperparathyroid bone diseases, including rickets and osteitis fibrosa. Compared with normal controls, patients with PHP may exhibit similar, increased, or decreased bone mineral density. Higher bone mineral density has been found in patients with PHP type 1A than in normal controls, whereas decreased bone mass, osteosclerosis, and osteitis fibrosa cystica have been reported in patients with PHP type 1B, indicating more variable bone phenotypes in PHP type 1B. Bone tissues show partial sensitivity to parathyroid hormone in patients with PHP, leading to heterogeneous reactions to parathyroid hormone in different individuals and even in different regions of bone tissues in the same individual. Regions rich in cancellous bone are more sensitive and show more obvious improvement after therapy. Active vitamin D and calcium can significantly improve abnormal bone metabolism in patients with PHP.

Radiation osteitis: incidence and clinical impact in the setting of radiation treatment for soft tissue sarcoma.

OBJECTIVE: Radiotherapy is an important component of soft tissue sarcoma management. Radiation osteitis is a common radiographic finding identified in the setting of radiotherapy on magnetic resonance imaging (MRI). This study aims to identify the incidence of radiation osteitis in patients who received radiotherapy for soft tissue sarcoma and if a further workup, including a biopsy, was performed for concerning MRI findings. MATERIALS AND METHODS: Medical records of patients with soft tissue sarcoma who received radiotherapy from 2008 to 2020 were retrospectively reviewed. Patients with at least one MRI of the sarcoma site following radiotherapy and information regarding radiotherapy treatments were included. MRIs of these patients were reviewed for the presence of radiation osteitis by two musculoskeletal radiologists. The clinical course of these patients including biopsy for concerning MRI findings, local recurrence, and metastasis was recorded. RESULTS: Thirty soft tissue sarcoma patients who received radiation for soft tissue sarcoma were included. Radiation osteitis was present in 18 patients. The time to osteitis present on MRI following radiotherapy completion was a median of 4.5 months. Biopsy for concerning MRI findings was performed in eight patients, five for local recurrence, and three for regional osseous metastasis. Three patients had confirmed osseous metastases. CONCLUSION: Although radiation osteitis is often a benign imaging finding, it can be difficult to discern these lesions from potentially malignant sites of disease. We recommend multidisciplinary management of soft tissue sarcoma at sarcoma centers to appropriately identify benign from malignant lesions and decide the necessity of a biopsy.

Effectiveness of the platelet-rich fibrin in the control of pain associated with alveolar osteitis: a scoping review.

OBJECTIVES: The aim of this scoping review was to determine the effectiveness of the platelet-rich fibrin in the control of pain associated with alveolar osteitis. MATERIALS AND METHODS: Reporting was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. A literature search was conducted in the PubMed and Scopus databases to identify all clinical studies on the application of platelet-rich fibrin in the control of pain caused by alveolar osteitis. Data were extracted independently by two reviewers and qualitatively described. RESULTS: The initial search returned 81 articles, with 49 identified after duplicates removal; of these, 8 were selected according to the inclusion criteria. Three of the eight studies were randomized controlled clinical trials, and four were non-randomized clinical studies, two of which were controlled. One study was case series. In all of these studies, pain control was evaluated using the visual analog scale. Overall, the use of platelet-rich fibrin resulted effective in the control of pain determined by alveolar osteitis. CONCLUSIONS: Within the limits of this scoping review, the application of platelet-rich fibrin in the post-extra-extraction alveolus reduced the pain associated with alveolar osteitis in almost all the included studies. Nevertheless, high-quality randomized trials with adequate sample size are warranted to draw firm conclusions. CLINICAL RELEVANCE: Pain associated with alveolar osteitis causes discomfort to the patient and is challenging to be treated. Use of platelet-rich fibrin could be a promising clinical strategy for pain control in alveolar osteitis if its effectiveness will be confirmed by further high-quality studies.

Assessment of clinical and radiological characteristics of Japanese patients with SAPHO syndrome.

OBJECTIVE: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. METHODS: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34, mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. RESULTS: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying anti-rheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. CONCLUSION: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

The Impact of Spray Cryotherapy on Lesion-Induced Osteitis in a New Murine Experimental Model.

Background and Objectives: Endoscopic sinus surgery is considered the gold management strategy for difficult-to-treat chronic rhinosinusitis. The inflammatory bony process is incriminated as being involved in the unfavorable evolution and recurrence of the disease. Osteitis is significantly increased in patients that have been previously submitted to surgery, and it is more often present in patients with extended radiological disease and in patients undergoing revision surgery. The aim of the research is to demonstrate the presence of inflammations and neo-osteogenesis associated with nasal mucosal surgical injury and the correlation between their severity and to evaluate the efficacy of low-pressure spray cryotherapy in reducing inflammation and bone remodeling. Materials and Methods: The experimental murine model was conducted over a period of 80 days and included a total of 60 adult female Wistar rats, with three periods of withdrawal of 20 individuals each from the experiment. After inducing a bilateral mechanical injury by brushing, low-pressure spray cryotherapy application was performed unilaterally, and tissue samples were prepared specifically for histological analysis. The scores for inflammation and osteitis were compared over time and between the two nasal fossae. Results: Osteitis and inflammation were induced by a simple mucosal brushing lesion, similar to surgical injury. We identified the presence of inflammation in 95% of the specimens, and it was present over time. Moreover, criteria for bone remodeling were clearly highlighted in a percentage of 72% of the specimens. There was a direct correlation between the severity of inflammation and neo-osteogenesis, with a statistical significance of p = 0.050. Low-pressure spray cryotherapy was safe and effective in reducing inflammation (p = 0.020) and osteitis (p = 0.000) with a safety profile. Conclusions: Low-pressure cryotherapy reduces the severity of mucosal inflammation and osteitis in lesion-induced neo-osteogenesis.

Successful treatment of SAPHO syndrome (chronic nonbacterial osteomyelitis and acne) with anakinra and denosumab. Case report and review of therapy.

SAPHO is an acronym derived from capital letters of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO). SAPHO syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations. A 40-year-old male complained about his jaw and back pain, swelling of multiple joints and weight loss accompanied by physical deterioration and acne type skin lesions. Laboratory tests revealed abnormal elevation of inflammatory markers. Imaging studies illustrated multiple osteolytic bone lesions and paraosseal infiltrates. According to the set of criteria diagnosis of SAPHO syndrome was stated. The patient was treated with glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), but only high dose dexamethasone and prednisone were effective. Daily subcutaneous administration of anakinra at the dose of 100 mg was initiated due to limited response to more classical therapies. Because of planned mandibular osteosynthesis initiation of denosumab was preferred before bisphosphonates. Therapeutic response was confirmed by FDG-PET/MR after 5 months of anakinra and denosumab therapy, showing decreased accumulation of FDG in periosteal and paraosseal infiltrates. Inflammatory markers significantly decreased, bone pain deferred but skin manifestation receded only partially. Therefore the response was evaluated as partial remission.

Diagnosing Fracture-Related Infections: Where Are We Now?

Accurate diagnosis of fracture-related infection (FRI) is critical for preventing poor outcomes such as loss of function or amputation. Due to the multiple variables associated with FRI, however, accurate diagnosis is challenging and complicated by a lack of standardized diagnostic criteria. Limitations with the current gold standard for diagnosis, which is routine microbiology culture, further complicate the diagnostic and management process. Efforts to optimize the process rely on a foundation of data derived from prosthetic joint infections (PJI), but differences in PJI and FRI make it clear that unique approaches for these distinct infections are required. A more concerted effort focusing on FRI has dominated more recent investigations and publications leading to a consensus definition by the American Orthopedics (AO) Foundation and the European Bone and Joint Infection Society (EBJIS). This has the potential to better standardize the diagnostic process, which will not only improve patient care but also facilitate more robust and reproducible research related to the diagnosis and management of FRI. The purpose of this minireview is to explore the consensus definition, describe the foundation of data supporting current FRI diagnostic techniques, and identify pathways for optimization of clinical microbiology-based strategies and data.

Revisiting the Case of Sarah Newbury's Death from Mollities Ossium.

Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case.