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Context: Osteitis pubis (OP), which occurs as a result of excessive use of the symphysis pubis and parasymphysis bones, is more common in long-distance runners and kicking athletes, especially football players. Due to the poor results of commonly used treatments for OP, there is a need for investigation of more effective treatments, such as ozone therapy. Ozone therapy is used to treat a variety of diseases, including musculoskeletal conditions. Case Presentation: A 30-year-old amateur soccer player diagnosed with OP received conservative treatment with traditional physiotherapy and analgesic medications. After 6 months and no resolution of symptoms, the patient presented to the sports medicine outpatient clinic seeking alternative therapy options. Management and Outcomes: The patient received ozone injections in 3 sessions administered at 10-day intervals. At 1, 3, 6 and 12 months after the treatment, the patient's complaints and pain levels were re-evaluated and examined. The patient was able to return to competition at the same level after the first injection. No recurrence was revealed at a minimum of 12 months of follow-up. Conclusion: In this article, we present a case in which OP was successfully treated with ozone injection. [ABSTRACT FROM AUTHOR]

Background: Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection. Results: The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis–induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice. Conclusions: High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients. [ABSTRACT FROM AUTHOR]

Objectives: Chronic rhinosinusitis (CRS) is a common disease with mucosal inflammation, and may sometimes be accompanied by bone thickening. The disease is usually bilateral; when it is unilateral, there may be a specific disease. This study aimed to investigate the association between unilateral sinus opacification and osteitis. Methods: In total, 104 patients with computed tomography revealing unilateral sinus opacification were included in this study. Patients were retrospectively evaluated using the Global Osteitis Scoring Scale (GOSS) score, Lund–Mackey (LM) score, polyp score, and blood tests. Results: In total, 47, 11, 9, 17, and 20 patients had CRS, paranasal sinus cyst, inverted papilloma, mycetoma, and odontogenic sinusitis, respectively. The GOSS score in patients with mycetoma was higher than that in patients with CRS. However, no significant differences in the GOSS scores between patients with mycetoma, inverted papilloma, and odontogenic sinusitis existed. 10 of the 104 patients had osteitis with extensive bone thickening and a GOSS score of 4 or higher. Patients with CRS and mycetoma tended to have a higher GOSS score for the maxillary sinus than for the other sinuses. There was a significant positive correlation between the GOSS score and LM score in patients with diseases other than paranasal sinus cyst. Conclusions: Mycetoma is more likely to cause osteitis than CRS, and a unique mechanism of osteitis exacerbation is predicted. As there is a positive correlation between bone thickening and sinus inflammation, a close association between osteitis and mucosal inflammation is inferred in diseases involving unilateral sinus opacification. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical and surgical characteristics of external fixation technique to manage complex open proximal humerus fractures caused by high-energy firearm injuries at the Hospital Militar Central, Colombia. Methods: A retrospective case series of patients with open complex proximal humerus fractures (Gustilo & Anderson III A-B or Neer III and IV) caused by long range or fragmentation weapons treated with external fixation. The variables are demographic data, range of motion, consolidation measurements, and functional outcomes according to the Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH) functional scale. Results: Seven male patients, with high-energy injuries causing open complex proximal humerus fractures (Gustilo & Anderson III A-B or Neer III or IV) underwent surgical treatment with external fixation and arthrodiastasis. Median age was 21.0 (19–24) years, mean treatment duration was 5.6 (4–7) months, and all patients completed 15 months of follow-up. Mean postoperative active movement measurements were flexion: 80° (40°–120°), abduction 85.7° (40°–130°), external rotation: 24.7° (10°–45°), and internal rotation: 23.6° (10°–45°). Mean postoperative pain according to visual analog scale was 2.7 (1–4) and mean Quick DASH was 36.2 (15.9–58). Two patients presented postoperative complications, one case each of infection and osteitis. Conclusion: Complex open proximal humeral fractures caused by high-energy trauma treated with transarticular external fixation via arthrodiastasis show promising short-term and mid-term results with low complication rates, low levels of postoperative pain, and moderate functional results. This external fixation technique seems to be a valid option for the treatment of polytraumatic patients with humeral injuries. Longer follow ups and larger sample sizes studies must be presented to better characterize the clinical and satisfaction outcomes. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, mainly characterized by perifibrocartilage osteitis of the sacroiliac joints and spinal enthesitis. To date, the exact pathogenesis of AS remains elusive. It is generally believed that AS is a multifactorial disease involving genetics, infection, environment, and immunity. Among them, genetic factors are the primary determinants of disease risk and severity. In recent years, epigenetic mechanisms such as DNA methylation have been extensively surveyed with respect to the pathogenesis of AS. This review summarizes the latest research progress of methylation in AS, from whole-genome sequencing to individual differentially methylated gene. And finally, the role of methylase in AS inflammation, autophagy, and osteogenic differentiation was explored. In summary, the results of this review attempt to explain the role of methylation in the occurrence and development of AS and point out the shortcomings of current methylation research, providing directions for subsequent methylation research in AS. [ABSTRACT FROM AUTHOR]

This article comprehensively reviews current imaging concepts in spinal infection with primary focus on infectious spondylodiscitis (IS) as well as the less common entity of facet joint septic arthritis (FSA). This review encompasses the multimodality imaging appearances (radiographs, CT, MRI, and nuclear imaging) of spinal infection—both at initial presentation and during treatment—to aid the radiologist in guiding diagnosis and successful management. We discuss the pathophysiology of spinal infection in various patient populations (including the non-instrumented and postoperative spine) as well as the role of imaging-guided biopsy. We also highlight several non-infectious entities that can mimic IS (both clinically and radiologically) that should be considered during image interpretation to avoid misdiagnosis. These potential mimics include the following: Modic type 1 degenerative changes, acute Schmorl's node, neuropathic spondyloarthropathy, radiation osteitis, and inflammatory spondyloarthropathy (SAPHO syndrome). [ABSTRACT FROM AUTHOR]

Background: The surgical removal of a mandibular third molar (M3M) is a common procedure performed by oral and maxillofacial surgeons, oral surgeons and general dental practitioners. Apart from risks such as pain, swelling, bruising, bleeding, trismus, alveolar osteitis, postoperative infection and damage to adjacent structures, which are common to all surgical extractions, M3M removal includes the risk of permanent or temporary damage to the inferior alveolar nerve (IAN) or the lingual nerve. IAN damage can significantly impact on quality of life (QoL) due to an altered sensation of the lip and chin area. As such, the alternative surgical option of coronectomy, which is the sectioning of the crown from the tooth and deliberate retention of the roots, can be offered to high-risk cases to avoid IAN damage. Case presentation: A 36-year-old female patient was diagnosed with recurrent pericoronitis of her left M3M. Her left M3M was partially erupted and horizontally impacted, with bulbous roots that were in close proximity to the IAN. Due to a higher risk of IAN damage, she underwent a coronectomy procedure of her left M3M instead of a complete removal. She experienced typical postoperative pain and swelling, but no other complications such as altered nerve sensation were reported. The surgical site was healed with full mucosal coverage after 12 weeks. Conclusion: Coronectomy provides a viable alternative surgical option for removal of M3Ms that are at high risk of IAN damage. This is due to the significant reduction of risk of IAN damage and low incidence of failure. [ABSTRACT FROM AUTHOR]

Chronic nonbacterial osteitis (CNO) is a rare auto-inflammatory bone disease affecting children and adults. Adult CNO is characterized by painful bone lesions, primarily of the anterior chest wall. There is no approved therapy for adult CNO. Current off-label treatments include intravenous bisphosphonates, which have been shown to alleviate pain through decreasing bone turnover. However, no adequately powered randomized controlled trials (RCTs) have been conducted. This double-blind, placebo-controlled RCT investigates the efficacy of intravenous pamidronate to decrease bone pain in adult CNO patients. Recruiting at the Dutch national referral center for CNO, adult patients with persistent bone pain despite non-steroidal anti-inflammatory drugs, or optionally other standard-of-care treatments are randomized to receive two courses of intravenous pamidronate (at 0 and 3 mo, 30 mg daily, on 3 consecutive d) or placebo. From 6 mo onwards, all patients receive open-label pamidronate for another two courses. The primary outcome is change in score for maximum pain from 0 to 6 mo. Secondary outcomes include change in quantitative intralesional bone turnover as measured on sodium-fluoride positron emission computed tomography ([18F]NaF-PET/CT), inflammation markers, shoulder function, general health, quality of life, fatigue, physical, and work activity. The pamidronate for pain in adult chronic nonbacterial osteitis trial addresses the need for evidence-based treatments in adult CNO. Results will directly impact daily clinical practice, either validating the use of intravenous pamidronate in CNO at the dose used in this trial or prompting the search for alternative regimens or agents. This trial was registered in EudraCT (reference 2020-001068-27) and the Dutch Trial Register (reference NL68020.058.20). Lay Summary: Chronic nonbacterial osteitis (CNO) is a rare bone disease that causes painful bone lesions and affects both children and adults. CNO particularly affects the chest area in adults. Currently, there is no approved treatment for adult CNO, but some off-label treatments, such as intravenous bisphosphonates, have shown promise in reducing pain by lowering bone turnover. However, no clinical trials have confirmed their effectiveness. A new study, the pamidronate for pain in adult chronic nonbacterial osteitis trial aims to investigate whether intravenous pamidronate can effectively reduce bone pain in adults with CNO. This double-blind, placebo-controlled trial involves adult CNO patients who continue to experience bone pain despite taking non-steroidal anti-inflammatory drugs or optionally other medications. Participants are randomly assigned to receive either pamidronate or a placebo. They receive two courses of pamidronate at the start and again after 3 mo, followed by open-label pamidronate treatment from the 6-mo mark. The main goal of the trial is to measure changes in maximum pain levels over the first 6 mo. Secondary goals include assessing bone turnover using advanced imaging techniques, inflammation markers, shoulder function, general health, quality of life, fatigue, and physical and work activities. The results of this trial will provide valuable evidence on the effectiveness of intravenous pamidronate for treating adult CNO and will guide future treatment strategies, either confirming its use or suggesting the need for alternative treatments. Graphical Abstract [ABSTRACT FROM AUTHOR]

Acute pancreatitis, an acute inflammatory injury of the pancreas, lacks a specific treatment. The circulatory protein renalase is produced by the kidney and other tissues and has potent anti-inflammatory and prosurvival properties. Recombinant renalase can reduce the severity of mild cerulein pancreatitis; the activity is contained in a conserved 20 aa renalase site (RP220). Here, we investigated the therapeutic effects of renalase on pancreatitis using two clinically relevant models of acute pancreatitis. The ability of peptides containing the RP220 site to reduce injury in a 1-day post-endoscopic retrograde cholangiopancreatography (ERCP) and a 2-day severe cerulein induced in mice was examined. The initial dose of renalase peptides was given either prophylactically (before) or therapeutically (after) the initiation of the disease. Samples were collected to determine early pancreatitis responses (tissue edema, plasma amylase, active zymogens) and later histologic tissue injury and inflammatory changes. In both preclinical models, renalase peptides significantly reduced histologic damage associated with pancreatitis, especially inflammation, necrosis, and overall injury. Quantifying inflammation using specific immunohistochemical markers demonstrated that renalase peptides significantly reduced overall bone marrow-derived inflammation and neutrophils and macrophage populations in both models. In the severe cerulein model, administering a renalase peptide with or without pretreatment significantly reduced injury. Pancreatitis and renalase peptide effects appeared to be the same in female and male mice. These studies suggest renalase peptides that retain the anti-inflammatory and prosurvival properties of recombinant renalase can reduce the severity of acute pancreatitis and might be attractive candidates for therapeutic development. NEW & NOTEWORTHY: Renalase is a secretory protein. The prosurvival and anti-inflammatory effects of the whole molecule are contained in a 20 aa renalase site (RP220). Systemic treatment with peptides containing this renalase site reduced the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) and severe cerulein pancreatitis in mouse models. [ABSTRACT FROM AUTHOR]

Langerhans histiocytosis or histiocytosis X is an oligo-clonal proliferation of Langerhans cells. We report the case of an 11-month-old infant who had presented with a parieto-occipital swelling since birth, which progressively increased in volume without any other presenting signs. The radiological work-up initially suspected osteitis of the vault, which was removed in its entirety. The anatomopathological study concluded that it was histiocytosis X. The extension work-up was negative. Follow-up of this patient showed no local recurrence or appearance of other localizations.A review of the literature shows that little is known about its pathophysiology. It mainly affects children and young adults. There are several possible sites of involvement, and cranial vault involvement is a fairly frequent form among the bony sites of this pathology. The diagnosis is confirmed histologically or cytologically, and extension workup is required to confirm the diagnosis. Therapeutic management has not been standardized, and sometimes requires chemotherapy in addition to surgery. The prognosis depends on whether vital organs are affected or not.

Alkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion. Lumbar spinal fusion procedures from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44–147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications. A total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83–11.97), pneumonia (OR 2.89, 95% CI 1.59–5.25), requiring a transfusion (OR 2.09, 95% CI 1.68–2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12–2.52), readmission within 30 days (OR 1.60, 95% CI 1.16–2.21), increased length of stay (OR 1.87, 95% CI 1.49–2.36), and nonhome discharge (OR 2.18, 95% CI 1.80–2.66). Elevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether a progressive marginal bone loss (PMBL) occurring beyond the initial bone remodeling (IBR) is linked with bleeding on probing. Materials and Methods: A total of 70 partially edentulous patients exhibiting 112 two‐piece bone‐level implants were included in this retrospective study. Panoramic radiographs were obtained after implant insertion (T0), after delivery of a final prosthetic restoration (T1) and subsequently during the 1‐(T2), 5‐(T3), 10‐(T4), and 15‐years (T5) follow‐up visits. At each time point, radiographic marginal bone levels were assessed from the implant shoulder to the first bone‐to‐implant contact at mesial and distal aspects. The IBR was defined as a bone loss occurring up to prosthesis delivery, that is, from T0 to T1. The PMBL was defined as bone loss occurring after T1. At T2, T3, T4, and T5, the presence or absence of bleeding on probing (BOP) was recorded at four sites. A median regression with mixed models was performed to assess the difference of PMBL in PMBL + BOP+ and PBML + BOP− groups. Results: Over the mean implant functioning time of 4.44 ± 4.91 years, 38 (34%) implants showed no PBML, whereas 74 (66%) implants featured PMBL. Of these, 35 (47%) and 39 (53%) implants were assigned to the PMBL + BOP− and PMBL + BOP+ groups, respectively. The mean PMBL after 1, 5, 10, and 15 years were comparable between implants featuring PMBL with or without BOP. At 1 year, BOP intensity significantly correlated PMBL, with each increase in one BOP‐positive site being associated with increase in PMBL by 0.55 mm (p = 0.038), whereas this association was not found at 5, 10, and 15 years. The IBR values in the no PBML, PMBL + BOP+, and PBML + BOP− groups were −0.24 ± 0.31, −0.41 ± 0.59, and −0.24 ± 0.33 mm, respectively, with no significant differences found among the groups. Conclusion: Progressive bone loss at implant sites is not always linked with bleeding on probing. [ABSTRACT FROM AUTHOR]

Osteomyelitis is a bone inflammation caused by an infectious microorganism, which may lead to complete structure decay. Over time, along with the discovery and usage of powerful antibiotics, it became a rare occurrence in modern practice. In this paper, we will present a case of a patient with craniofacial osteomyelitis, which occurred as a complication of previous trauma and incomplete surgical treatment, due to lack of compliance. Chronic diseases in the non-cooperative patient led to the development of a severe clinical state. We believe that the existence of communication between defects on the anterior wall of the frontal sinus and corresponding subcutaneous and cutaneous tissue may have prevented further complications, in particular endocranial. Despite of a severe local finding, there was no dramatic increase in inflammatory parameters in laboratory analysis, as expected in such cases. A careful diagnostic procedure, identification of causative agent, adequately applied antibiotic therapy followed by surgical treatment debridement, improved the general condition of the patient as well as local finding. A severe form of osteomyelitis of the facial bones can be a complication after facial bone osteosynthesis. The absence of endocranial complications can be explained by drainage of purulent content through defects in the skin of the face. Quick and precise diagnostics, followed by treatment that includes a combination of surgery and conservative treatment, give the best results in such complex conditions. [ABSTRACT FROM AUTHOR]

Objective: To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO). Methods: Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15 years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study. Results: Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2 years; age at diagnosis, 10.3 ± 3.3 years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%). Conclusion: Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis. Clinical relevance statement: When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible. Key Points: • Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected. [ABSTRACT FROM AUTHOR]

There is a strong association between vitamin D levels and periodontal disease based on numerous epidemiological studies. We have previously shown that experimental deficiency of serum vitamin D in mice leads to gingival inflammation and alveolar bone loss. Treatment of cultured oral epithelial cells with the active form of vitamin D, 1,25(OH)2 vitamin D3 (1,25(OH)2D3), inhibits the extracellular growth and intracellular invasion of bacteria associated with periodontal disease. Maintenance of periodontal health may be due in part to the anti-inflammatory activities of vitamin D. Furthermore, this hormone can induce the expression of an antimicrobial peptide in cultured oral epithelial cells. We have shown that oral epithelial cells are capable of converting inactive vitamin D to the active form, suggesting that topical treatment of the oral epithelium with inactive vitamin D could prevent the development of periodontitis. We subjected mice to ligature-induced periodontitis (LIP), followed by daily treatment with inactive vitamin D or 1,25(OH)2D3. Treatment with both forms led to a reduction in ligature-induced bone loss and inflammation. Gingival tissues obtained from vitamin D–treated LIP showed production of specialized proresolving mediators (SPM) of inflammation. To examine the mechanism, we demonstrated that apical treatment of 3-dimensional cultures of primary gingival epithelial cells with vitamin D prevented lipopolysaccharide-induced secretion of proinflammatory cytokines and led to a similar production of SPM. Analysis of the oral microbiome of the mice treated with vitamin D showed significant changes in resident bacteria, which reflects a shift toward health-associated species. Together, our results show that topical treatment of oral tissues with inactive vitamin D can lead to the maintenance of periodontal health through the regulation of a healthy microbiome and the stimulation of resolution of inflammation. This strongly supports the development of a safe and effective vitamin D–based topical treatment or preventive agent for periodontal inflammation and disease. [ABSTRACT FROM AUTHOR]

Pathogenic variants in valosin-containing protein (VCP) cause multisystem proteinopathy (MSP), a disease characterized by multiple clinical phenotypes including inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (FTD). How such diverse phenotypes are driven by pathogenic VCP variants is not known. We found that these diseases exhibit a common pathologic feature: ubiquitinated intranuclear inclusions affecting myocytes, osteoclasts, and neurons. Moreover, knock-in cell lines harboring MSP variants show a reduction in nuclear VCP. Given that MSP is associated with neuronal intranuclear inclusions comprised of TDP-43 protein, we developed a cellular model whereby proteostatic stress results in the formation of insoluble intranuclear TDP-43 aggregates. Consistent with a loss of nuclear VCP function, cells harboring MSP variants or cells treated with VCP inhibitor exhibited decreased clearance of insoluble intranuclear TDP-43 aggregates. Moreover, we identified 4 compounds that activate VCP primarily by increasing D2 ATPase activity, where pharmacologic VCP activation appears to enhance clearance of insoluble intranuclear TDP-43 aggregate. Our findings suggest that VCP function is important for nuclear protein homeostasis, that impaired nuclear proteostasis may contribute to MSP, and that VCP activation may be a potential therapeutic by virtue of enhancing the clearance of intranuclear protein aggregates. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.Twenty‐four 70‐day‐old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP‐Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT‐PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one‐way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters.Micro‐CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti‐inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is a rare epithelial malignancy, and approximately 30%-40% of EMPD patients overexpress human epidermal growth factor receptor 2 (Her-2). Currently, there are no established standard treatments for advanced EMPD while anti-Her-2 therapy is recommended for Her-2-positive cases. Case presentation: Here, we report a 51-year-old male diagnosed with advanced Her-2-positive EMPD, presenting with numerous lymph node metastases. This patient received disitamab vedotin (an antibody-drug conjugate, targeting Her-2) combined with serplulimab as first-line treatment. After seven cycles of combination therapy, the patient tolerated the treatment well and the lymph node lesions continued to shrink. However, the patient developed immunotherapy-related pneumonia following the eighth treatment. Hormone therapy was administered while all the anti-tumor therapies were halted. After the pneumonia improved, the patient underwent positron emission tomography-computed tomography, revealing a complete response to his tumor. To consolidate the effect, he received another five cycles of disitamab vedotin monotherapy as maintenance therapy, without experiencing any adverse events. To date, the patient has remained in good health without any recurrence 10 months after drug discontinuance. Conclusion: Disitamab vedotin combined with immunotherapy demonstrated a long-term clinical benefit in advanced Her-2-positive EMPD. For rare solid tumors with Her-2 overexpression, disitamab vedotin combined with immunotherapy might offer a viable therapeutic choice. [ABSTRACT FROM AUTHOR]

Introduction: chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, that most commonly first appears in childhood. Symptoms can be nonspecific at first (fever, night sweats, fatigue), followed by bone pain, bone swelling, nocturnal pain, and impaired function of the affected part of the body. Diagnosis is usually delayed, because there are no widely accepted criteria for CNO, so differentialdiagnoses need to be excluded (malignancy, infection). It can be accompanied by severe complications (vertebral fractures). Case report: this case series presents three female patients who were diagnosed with chronic nonbacterial osteomyelitis. They were referred to a pediatric rheumatologist a minimum of eight months after the first symptoms occurred. The most frequent symptoms were nocturnal bone pain and swelling. None of the patients had a fever. The bones primarily affected were the clavicle, mandible, humerus and vertebra with secondary complications such as compressive vertebral fractures, and scoliosis. One developed paradoxical psoriasis while being treated with TNF inhibitors. Conclusion: this case report highlights the importance of considering chronic nonbacterial osteomyelitis as a potential cause of bone swelling and pain. The key factors for improving the outcome of patients with CNO are early recognition and timely treatment, as well as a multidisciplinary approach due to the complexity of the diagnosis. [ABSTRACT FROM AUTHOR]

Pubic symphysis, also known as osteitis pubis, is an inflammatory condition of the pubic symphysis, clinically characterized by severe pelvic pain, abnormal gait with the increased base of support, and bone destruction of the pubic symphysis margins. Initially associated with certain surgical interventions, speculation about its pathogenesis includes infection, trauma, local vascular anomalies, and reflex-sympathetic dystrophy. This confusion about its etiology is reflected in the wide variety of treatments that have been used over the years, including radiation, bed rest for long periods, infiltration with local anesthetics, anti-inflammatories nonsteroidal drugs, antibiotics, heparin, surgical debridement, wedge resection of the pubic symphysis, and autologous iliac bone transplantation. Both bony infection and inflammation of the pubic area are rare. In the medical literature these two entities have been frequently confused, so that many diagnosed cases of osteitis pubis have actually been shown to be misdiagnosed osteomyelitis pubis. For this reason, an aggressive diagnostic approach is recommended, especially in post-surgical cases, with biopsy and arthrocentesis of the symphysis guided by computed tomography. [ABSTRACT FROM AUTHOR]

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 antirheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. Conclusions: 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. [ABSTRACT FROM AUTHOR]

To report a case of bilateral retinal vasculitis successfully managed with adalimumab in a patient with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. SAPHO syndrome was diagnosed in a 48-year-old female with bilateral blurred vision refractory to steroid eye drops. A preliminary ophthalmic examination revealed bilateral intermediate uveitis with vitreous opacity, and fluorescein angiography (FA) revealed dye leakage from peripheral retinal vessels. Because oral antirheumatic drugs were ineffective in treating her osteitis, her internist prescribed adalimumab, which resulted in rapid normalization of C-reactive protein and improvement of osteitis. Following treatment with adalimumab for 5 months, FA revealed significant improvement of retinal vasculitis. This is the first report on the use of adalimumab for retinal vasculitis associated with SAPHO syndrome. We described a rare case of retinal vasculitis associated with SAPHO syndrome. Adalimumab treatment was effective in treating both osteitis and retinal vasculitis. [ABSTRACT FROM AUTHOR]

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-β (TGF-β). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway. [ABSTRACT FROM AUTHOR]

There has been growing interest in medical research focused on natural products. As a result of the ancestral knowledge passed down through generations and the demands of our current era, there has been an increased demand for new strategies and the search for new molecules with therapeutic potential. This increase is due to new technologies, the evolution of diseases, and the emergence of new ones. In this review, we focus on the work and relevance of Curcumin research, which is one of the main components of Curcuma longa. Additionally, we explore Amaranth in its various reported species and components (seed, leaf, stem) studied. The focus is on the anti-inflammatory therapeutic potential, not only in one, but in different diseases characterized by inflammation and bone destruction. We aim to analyze the possible molecular mechanisms by which curcumin and amaranth act as well as data currently obtained from different studies. This review aims to open a new perspective to the investigation of these compounds in the field of diseases characterized by inflammation and bone destruction. [ABSTRACT FROM AUTHOR]

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Periodontal disease is a chronic inflammatory condition that affects the supporting structures of the teeth, including the periodontal ligament and alveolar bone. Periodontal disease is due to an immune response that stimulates gingivitis and periodontitis, and its systemic consequences. This immune response is triggered by bacteria and may be modulated by environmental conditions such as smoking or systemic disease. Recent advances in single cell RNA-seq (scRNA-seq) and in vivo animal studies have provided new insight into the immune response triggered by bacteria that causes periodontitis and gingivitis. Dysbiosis, which constitutes a change in the bacterial composition of the microbiome, is a key factor in the initiation and progression of periodontitis. The host immune response to dysbiosis involves the activation of various cell types, including keratinocytes, stromal cells, neutrophils, monocytes/ macrophages, dendritic cells and several lymphocyte subsets, which release proinflammatory cytokines and chemokines. Periodontal disease has been implicated in contributing to the pathogenesis of several systemic conditions, including diabetes, rheumatoid arthritis, cardiovascular disease and Alzheimer’s disease. Understanding the complex interplay between the oral microbiome and the host immune response is critical for the development of new therapeutic strategies for the prevention and treatment of periodontitis and its systemic consequences. [ABSTRACT FROM AUTHOR]

To address and regenerate infected bone defects complicated by issues such as inflammation and bone resorption, and to promote bone regeneration, this study focuses on the development of a composite scaffold with reactive oxygen species (ROS)‐scavenging and bacteria‐resistant properties. The composite scaffold integrates a self‐assembled small intestinal submucosa (SIS) hydrogel with pre‐adsorbed hydroxyapatite (HA) particles and tannic acid (TA), demonstrating distinctive mechanical resilience and porous structures, suitable for filling irregular cavities and facilitating cell infiltration, while exhibiting a broad‐spectrum of antibacterial efficacy and robust ROS‐scavenging capacity for tissue regeneration. RNA‐sequencing analysis indicates the underlying mechanism revealing the disrupting of arginine and alanine amino acid biosynthesis. Furthermore, the composite scaffold demonstrates excellent cytocompatibility, with cell viability exceeding 70%. Remarkably, it demonstrates exceptional anti‐inflammatory performances (≈5‐fold to the control). In an infected bone defect model, the composite scaffold facilitates superior bone regeneration, being ≈5‐fold greater than the control, while maintaining a conducive environment for cell adhesion and infiltration without scaffold collapse. This multifunctional composite scaffold emerges as a promising candidate for combating infections in bone regeneration, showcasing its potential in addressing complex bone‐related challenges. [ABSTRACT FROM AUTHOR]

Background: External ear canal exostoses are usually bilateral and broad-based, secondary to external ear canal chronic cold exposure, especially water. Objectives: The objectives were to analyze the influence of the surgeon's experience on the 3-year recurrence and on the complication. We also studied the influence of prolonged exposure to cold water on the incidence of recurrence. Material and Methods: This monocentric retrospective study included 98 ears operated for canalplasty between 2009 and 2016 by nine different operators including one senior, a junior, and seven beginner surgeons. Senior, Junior, and Beginner groups were compared. Results: 3-year recurrence rate was higher in the Beginner and Junior groups than in the Senior group (69% and 38% vs 18%, P =.001). Although there was a difference between the Beginner (69%) and Junior (38%) groups, it was not significant (P =.407). Among the recurrences, 48% had continued exposure to cold water while only 7% of the ears without recidivism were still exposed (P <.001, OR = 1.25 [4.4; 36.1]). The complication rates were similar between groups, concerning pain (8% vs 30% vs 12%), per procedure perforation (17% vs 10% vs 16%), scarring disorders (25% vs 20% vs 13%), and osteitis (8% vs 0% vs 1%). Hearing was unaffected. Conclusions: This is the first study evaluating the risk of recurrence of external ear canal exostoses after canalplasty based on the surgeon's experience. This risk of recurrence seems to decrease with the surgeon's experience. There was no difference in complication rates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The presence of osteoid bone in chronic rhinosinusitis especially the eosinophilic subtype is commonly associated with recalcitrant illness. In practice, the radiological features of osteitis sinus alterations are frequently described, but the clinical and histopathologic implications are not well understood. Objective: This study was done to correlate the radiological and the clinico-histopathological aspects in patients of eosinophilic chronic rhinosinusitis. Methods: A cross-sectional study was done on sixty patients of chronic rhinosinusitis with nasal polyposis (CRSwNP) patients especially the eosinophilic subtype undergoing sinus surgery. Radiologically, osteitis was graded using standards that had already been published in the literature. Analysis was done on the relationships between CT documented osteitis, histopathological, and peripheral eosinophilic counts in patients of eosinophilic chronic rhinosinusitis. Results: The patients with higher tissue eosinophilia and higher peripheral eosinophils had higher osteitis score. Pearson's correlation coefficient between Tissue Eosinophils and KOS was highly significant with p-value <0.001 (0.891). R2 value for KOS versus Tissue Eosinophils was 79.44%,implying that 79.44% variations were explained by Tissue Eosinophils in KOS. And R2 value for KOS versus Peripheral Eosinophils was 74.26%, implying that 74.26% variations were explained by Peripheral Eosinophils in KOS. Thereby, showing a positive relationship between the variables that were studied. Conclusion: Kennedy Osteitis Score, histopathological and peripheral eosinophilia can be used as a marker to predict the disease severity in eosinophilic chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P< 0.001), periosteal proteins (P< 0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P< 0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Purpose: The growing incidence of implant-associated infections (IAIs) caused by biofilm-forming Staphylococcus aureus in combination with an increasing resistance to antibiotics requires new therapeutic strategies. Lysostaphin has been shown to eliminate this biofilm. Own studies confirm the effectiveness in a murine model. The current study characterizes the effects of lysostaphin-coated plates in an IAI minipig model. Methods: The femur of 30 minipigs was stabilized with a five-hole plate, a bone defect was created, and in 20 cases methicillin-resistant Staphylococcus aureus was applied. Ten animals served as control group. After 14 days, local debridement, lavage, and plate exchange (seven-hole plate) were performed. Ten of the infected minipigs received an uncoated plate and 10 a lysostaphin-coated plate. On day 84, the minipigs were again lavaged, followed by euthanasia. Bacterial load was quantified by colony-forming units (CFU). Immunological response was determined by neutrophils, as well as interleukins. Fracture healing was assessed radiologically. Results: CFU showed significant difference between infected minipigs with an uncoated plate and minipigs with a lysostaphin-coated plate (p = 0.0411). The infection-related excessive callus formation and calcification was significantly greater in the infected animals with an uncoated plate than in animals with a lysostaphin-coated plate (p = 0.0164/p = 0.0033). The analysis of polymorphonuclear neutrophils and interleukins did not reveal any pioneering findings. Conclusion: This study confirms the minipig model for examining IAI. Furthermore, coating of plates using lysostaphin could be a promising tool in the therapeutic strategies of IAI. Future studies should focus on coating technology of implants and on translation into a clinical model. [ABSTRACT FROM AUTHOR]

Background: Acute hemorrhage is fatal in equines with a complication of severe hypovolemic shock that causes a sudden death in such cases. Aim: This study was designed to report the influences of acute bleeding in conscious non-sedated donkeys (Equus asinus) on the hematobiochemical variables, acid-base, blood gas elements, and markers of inflammation and bone metabolism. Methods: Eight healthy donkeys were used where a total of 900 ml of whole blood was collected. Five blood samples were collected from each animal: just before collection of blood (T0); (2) 30 (T1), 60 (T2), 120 (T3), and 240 minutes (T4) later. The blood panels including total white blood cells, lymphocytes, neutrophils, red blood cell counts (RBCs), HCT, hemoglobin (Hg), and RBCs indices were measured. Biochemical parameters and electrolytes were evaluated. The activity of aspartate aminotransferase (AST), creatine kinase (CK), and 1-glutamyl transferase (GGT) were also determined. Complete acid-base and blood gas panels were assessed. Serum amyloid A (SAA), haptoglobin (Hp), osteocalcin (OC), bone alkaline phosphatase (b-ALP), and pyridinoline cross-links (PYD) were measured. Results: The RBCs, Hg, and HCT increased significantly at points T1, T2, and T3 compared to T0. The concentrations of total proteins and albumin decreased significantly at points T3 and T4. The blood urea nitrogen concentrations increased significantly at T4. Creatinine concentrations increased significantly at T2 and T3. The AST, GGT, and CK decreased significantly. On the other hand, glucose increased significantly at T3 and T4. The pH decreased significantly at points T1, T2, T3, and T4. The PCO2 increased significantly at T3 and T4. The BE, HCO3, and TCO2 values decreased significantly at T2, T3, and T4. Contrary, the AG increased significantly at points T3 and T4. The potassium increased significantly at T1-T4 and chloride decreased significantly at T3 and T4. Lactate showed significant increases at T1-T4. The SAA, Hp, OC, b-ALP, and PYD did not differ significantly at T1-T4. Conclusion: In conscious non-sedated donkeys, induced bleeding resulted in significant changes in the hematobiochemical elements, the acid-base status, and blood gas and electrolyte parameters. However, it did not change the markers of inflammation and bone metabolism. [ABSTRACT FROM AUTHOR]

Osteitis of the sternocostoclavicular (SCC) region, referred to as sternocostoclavicular hyperostosis (SCCH), is the clinical expression of chronic non-bacterial osteitis (CNO) in adults with this rare chronic auto-inflammatory disorder of the axial skeleton. The diagnosis is based on distinctive computerized tomography (CT) features of sclerosis and hyperostosis of the SCC region, and local increases in osteoid formation visualized by high radiopharmacon uptake on skeletal scintigraphy but clear radiologic diagnostic criteria are lacking. In a cross-sectional study, CT scans and whole-body skeletal scintigraphy images obtained in 169 patients seen at the Center for Bone Quality of the Leiden University Medical Center between 2008 and 2018 with a suspected diagnosis of CNO of the SCC region were re-evaluated by 2 skeletal radiologists and 2 nuclear physicians. The diagnosis was confirmed in 118 (70%) predominantly female patients (n  = 103, 89.2%); median age at first symptoms 45 years (range 20-73). The diagnosis was excluded in the remaining 51 "non-CNO" patients. Increased radiopharmacon uptake at the SCC region was observed in 82% CNO patients, with the manubrium sterni having the highest predictive ability to discriminate on both imaging modalities. The prevalence of sclerosis of the clavicles, manubrium and first ribs was significantly higher in CNO patients (P  < 0.001). Hyperostosis was not observed in non-CNO patients. 46 CNO versus only 2 non-CNO patients had costoclavicular ligament calcification. Our findings identify CT scan features of sclerosis and hyperostosis of manubrium sterni, medial end of clavicles and first ribs, and calcification of costoclavicular ligaments, associated with increased tracer uptake on skeletal scintigraphy at the SCC region, specifically manubrium sterni, as well-defined imaging diagnostic criteria for adult CNO. Pitfalls encountered in the diagnosis of CNO are highlighted. These defined imaging diagnostic criteria for adult CNO should facilitate the diagnosis of this rare auto-inflammatory bone disease across the spectrum of its early to late stages. [ABSTRACT FROM AUTHOR]

T cells are adaptive immune cells essential in pathogenic response, cancer, and autoimmune disorders. During the integration of biomaterials with host tissue, T cells modify the local inflammatory environment by releasing cytokines that promote inflammatory resolution following implantation. T cells are vital for the modulation of innate immune cells, recruitment and proliferation of mesenchymal stem cells (MSCs), and formation of functional tissue around the biomaterial implant. We have demonstrated that deficiency of αβ T cells promotes macrophage polarization towards a pro-inflammatory phenotype and attenuates MSC recruitment and proliferation in vitro and in vivo. The goal of this study was to understand how CD4+ and CD8+ T cells, subsets of the αβ T cell family, impact the inflammatory response to titanium (Ti) biomaterials. Deficiency of either CD4+ or CD8+ T cells increased the proportion of pro-inflammatory macrophages, lowered anti-inflammatory macrophages, and diminished MSC recruitment in vitro and in vivo. In addition, new bone formation at the implantation site was significantly reduced in T cell-deficient mice compared to T cell-competent mice. Deficiency of CD4+ T cells exacerbated these effects compared to CD8+ T cell deficiency. Our results show the importance of CD4+ and CD8+ T cells in modulating the inflammatory response and promoting new bone formation in response to modified Ti implants. CD4+ and CD8+ T cells are essential in modulating the peri-implant microenvironment during the inflammatory response to biomaterial implantation. This study shows that deficiency of either CD4+ or CD8+ T cell subsets altered macrophage polarization and reduced MSC recruitment and proliferation at the implantation site. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Osteomyelitis of the elbow is a rare but potentially serious inflammatory condition affecting the elbow joint. The condition is characterized by infection of the bone and surrounding tissue, usually caused by pathogenic bacteria. Although less frequent than osteomyelitis seen in other parts of the body, such as the hips or knees, elbow osteomyelitis requires special attention due to its complex localization and the diagnostic challenges it presents. Case Presentation: We will discuss the case of a 46-year-old patient who presented with an osteosynthesis-treated olecranon fracture and poor follow-up, who subsequently presented to the emergency department with osteomyelitis of the elbow. Conclusion: Elbow osteomyelitis is a complex and potentially devastating condition requiring a multidisciplinary clinical approach and early management. In light of the case study presented and the review of existing literature, several important conclusions can be drawn to improve the management of this condition. [ABSTRACT FROM AUTHOR]

Objective Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. Methods We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). Results In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P  = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P  < 0.001). Conclusions High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions. [ABSTRACT FROM AUTHOR]

Objective: Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA‐binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group. Methods: We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology. Results: In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single‐photon emission computed tomography. Interpretation: The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Hypertrophy of inferior turbinate (IT) may arise from soft tissue and/or bony enlargement and is most related to inflammatory rhinitis. We aimed to study and compare the histopathological changes in the IT mucosa, submucosa, and bone in chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP). Methods: The specimens of the IT in patients who underwent endoscopic sinus surgery and inferior turbinoplasty (ITplasty) were included and studied under the microscope in the high-power field. The changes in the mucosa, submucosa, and bone were studied, graded accordingly, and compared between the 2 groups. Results: In the mucosa, there was no significant difference in the polymorphonuclear neutrophils (PMN) and lymphocytic counts; however, the eosinophilic count in the mucosa was significantly higher in CRSwNP (P = .001). There was no significant difference in basement membrane thickness or subepithelial oedema. However, the lymphocyte count was higher in CRSsNP (P = .003), and the eosinophilic count was higher in CRSwNP (P = .001). The bone did not show inflammation. The significant osteitic changes in the bone were periosteal thickening with osteoblastic activity (P = .016). Conclusion: The mucosa and submucosa had a significant change in CRSwNP related to the eosinophilic infiltrates. In the submucosa, the lymphocyte count was significantly higher in CRSsNP. The osteitic changes seen were limited to periosteal thickening with minimal osteoblastic activity in both groups, but were significantly higher in CRSsNP. Hence, we can resect only the effected mucosa and spare bone during ITplasty in cases of CRSwNP, and IT bone may be partly resected in CRSsNP patients [ABSTRACT FROM AUTHOR]

The benefits of probiotics on dysbiotic microbiomes and inflammation are dependent on the tested strain, host factors, and the resident microbiome. There is limited knowledge on the effects of probiotics in A. actinomycetemcomitans-associated periodontitis. Thus, Lactobacillus acidophilus LA5 (LA5) was orally inoculated for 30 days in C57Bl/6 mice infected with A. actinomycetemcomitans JP2 (Aa) and S. gordonii (Sg). Alveolar bone loss, gingival gene expression, and oral and gut microbiomes were determined. LA5 controlled bone loss in Aa+Sg-infected mice, downregulated the expression of Il-1β and upregulated Il-10 in gingival tissues, and altered the oral and gut microbiomes. LA5 increased the diversity of the oral microbiome of Aa+Sg infected mice, and Aa+Sg and Aa+Sg+LA5 oral or gut microbiomes clustered apart. LA5 induced shifts in Aa+Sg infected mice by increasing the abundance of Muribaculaceae and decreasing Bifidobacteriaceae in the oral cavity and increasing the abundance of Verrucomicrobiae and Eggerthellales in the gut. In conclusion, LA5 oral administration controls experimental Aa-associated periodontitis by altering inflammatory gene expression and the oral and gut microbiomes. [ABSTRACT FROM AUTHOR]

SAPHO syndrome is a complex disease that encompasses both inflammatory arthritis and/or osteitis and dermatologic manifestations. It is considered a rare disease, in fact, no clinical trials have been conducted on its therapy and management. Therefore, therapeutic approach is based on small case studies. Here, we described the case of a 63-year-old woman affected by SAPHO syndrome, treated with the selective IL-23p19 antagonist, Risankizumab, after unsuccessful therapies with Methotrexate, Infliximab, Adalimumab, and an allergic reaction to Secukinumab. At the beginning of therapy, in November 2022, the patient presented with arthritis in both knees associated with palmar pustulosis and guttate psoriasis on the trunk. DAPSA score was 24, PtGA 80 mm, PASI score 11.1, and BSA 40%. Thereafter, Risankizumab was started at the standard dosage of 150 mg. At week 24 patient achieved clinical remission, DAPSA score was 8, PtGA was 30 mm, PASI was 1, and BSA 2.5. Patient maintained clinical remission state at the subsequent week 52 evaluation. At the same time, the patient did not report any adverse effects. Health-related quality of life was also assessed at the same time points aforementioned, showing significant improvement. In conclusion, this case report wants to point out the efficacy and safety of Risankizumab in SAPHO syndrome, reporting a sustained disease remission through a 12 months long follow-up period. We can consider IL-23p19 targeted therapy as a novel treatment option for SAPHO—with a high efficacy potential—especially on patients that have already been treated with other biologics. [ABSTRACT FROM AUTHOR]

Introduction: Chronic non-bacterial osteomyelitis (CNO) is a rare, non-infection- related inflammatory disorder that affects children and teens. Clinical manifestations of CNO range widely from moderate, time-limited, monofocal inflammation of the bone to extreme multifocal or chronically active inflammation of the bone. Objectives: The main aim of this study was to explore the correlation between musculoskeletal (MSK) symptoms and health-related quality of life (HRQoL) in patients with CNO. Methods: Children and adults with CNO and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical and therapeutic data, MSK discomfort form based on the Nordic MSK Questionnaire and HRQoL based on Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL rheumatology module. The inclusion criteria included diagnosis of CNO before the age of 18. Patients who had malignancies or any chronic rheumatic, MSK, neurological disease prior to CNO onset were excluded. Results: There was a total of 68 participants, mostly females (66.2%), with median age 14 years and median disease duration 4.75 years. The median number of bones affected by CNO was 5 and ranged from 1 to 24 bones. Among the studied patients, 45 patients (66.2%) had MSK manifestations at the last month. The most commonly affected part was ankle and feet (26.5%). Regarding HRQoL, patients with MSK manifestations had lower scores than did patients without in PedsQL-4 (p < 0.001) including domains of physical functioning (p < 0.001), emotional functioning (p = 0.033), social functioning (p < 0.001) and school functioning (p = 0.007) in addition to lower scores in PedsQL rheumatology module (p < 0.001) including domains of pain and hurt (p < 0.001), daily activities (p < 0.001), treatment (p = 0.035), worry (p = 0.001) and communication (p < 0.001). Conclusion: MSK manifestations have a negative impact on HRQoL in CNO patients. So, early identification and treatment are highly recommended. [ABSTRACT FROM AUTHOR]

Alveolar bone resorption caused by bacteria‐induced periodontitis remains challenging due to sustained inflammation. Periodontal pathogens like Porphyromonas gingivalis launch the primed signal of NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome in macrophages; consequent overproduction of proinflammatory cytokines and reactive oxygen species (ROS) leads to tissue destruction. This provides potential targets for a new therapeutic strategy. Herein, a multifunctionalized and dual‐crosslinked hydrogel pGM/cPL@NI with NLRP3 inhibitor MCC950 loaded is prepared. Driven by the strategic functionalization of gelatin methacryloyl and ε‐poly‐lysine with phenylboronic acid and catechol, respectively, pGM/cPL@NI containing dynamic and photo‐crosslinking networks demonstrates superior mechanical strength and stimuli‐responsive behavior, as well as the overwhelmed performance in bacteria killing and ROS scavenging. Crucially, pGM/cPL@NI restores the compromised osteogenesis by specifically suppressing the proinflammatory cytokine cascade triggered by NLRP3 inflammasome activation and promoting anti‐inflammatory polarization of macrophages. Collectively, pGM/cPL@NI presents robust potential as an effective "cocktail therapy" by combining antibacterial, antioxidant, inflammation resolution, and tissue regenerative functions. The present study reveals the underlying mechanism of the bacterial‐immune‐regeneration cascade and provides an extended approach for periodontal tissue engineering. [ABSTRACT FROM AUTHOR]