PIM Kinases as Potential Biomarkers and Therapeutic Targets in Inflammatory Arthritides.

The Proviral Integration site for the Moloney murine leukemia virus (PIM)-1 kinase and its family members (PIM-2 and PIM-3) regulate several cellular functions including survival, proliferation, and apoptosis. Recent studies showed their involvement in the pathogenesis of rheumatoid arthritis RA, while no studies are available on psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). The main objective of this study is to assess the expression of PIM kinases in inflammatory arthritides, their correlation with proinflammatory cytokines, and their variation after treatment with biologic disease-modifying anti-rheumatic drugs or JAK inhibitors. We evaluated PIM-1, -2, and -3 expression at the gene and protein level, respectively, in the peripheral blood mononuclear cells and serum of patients with RA, PsA, axSpA, and healthy individuals (CTR). All the samples showed expression of PIM-1, -2, and -3 kinases both at the gene and protein level. PIM-1 was the most expressed protein, PIM-3 the least. PIM kinase levels differed between controls and disease groups, with reduced PIM-1 protein and increased PIM-3 protein in all disease samples compared to controls. No difference was found in the expression of these molecules between the three different pathologies. PIM levels were not modified after 6 months of therapy. In conclusion, our preliminary data suggest a deregulation of the PIM pathway in inflammatory arthritides. In-depth studies on the role of PIM kinases in this field are warranted.

A Vicious NGF-p75NTR Positive Feedback Loop Exacerbates the Toxic Effects of Oxidative Damage in the Human Retinal Epithelial Cell Line ARPE-19.

In spite of its variety of biological activities, the clinical exploitation of human NGF (hNGF) is currently limited to ocular pathologies. It is therefore interesting to test the effects of hNGF in preclinical models that may predict their efficacy and safety in the clinical setting of ocular disorders and compare the effects of hNGF with those of its analogs. We used a human retinal pigment cell line, ARPE-19 cells, to investigate the effects of hNGF and its analogs, mouse NGF (mNGF) and painless NGF (pNGF), on cell viability under basal conditions and after exposure to oxidative stimuli, i.e., hydrogen peroxide (H2O2) and ultraviolet (UV)-A rays. The effects of hNGF and pNGF were also tested on the gene expression and protein synthesis of the two NGF receptor subtypes, p75 neurotrophic receptors (p75NTR) and tyrosine kinase A (TrkA) receptors. We drew the following conclusions: (i) the exposure of ARPE-19 cells to H2O2 or UV-A causes a dose-dependent decrease in the number of viable cells; (ii) under baseline conditions, hNGF, but not pNGF, causes a concentration-dependent decrease in cell viability in the range of doses 1-100 ng/mL; (iii) hNGF, but not pNGF, significantly potentiates the toxic effects of H2O2 or of UV-A on ARPE-19 cells in the range of doses 1-100 ng/mL, while mNGF at the same doses presents an intermediate behavior; (iv) 100 ng/mL of hNGF triggers an increase in p75NTR expression in H2O2-treated ARPE-19 cells, while pNGF at the same dose does not; (v) pNGF, but not hNGF (both given at 100 ng/mL), increases the total cell fluorescence intensity for TrkA receptors in H2O2-treated ARPE-19 cells. The present findings suggest a vicious positive feedback loop through which NGF-mediated upregulation of p75NTR contributes to worsening the toxic effects of oxidative damage in the human retinal epithelial cell line ARPE-19. Looking at the possible clinical relevance of these findings, one can postulate that pNGF might show a better benefit/risk ratio than hNGF in the treatment of ocular disorders.

Building a rheumatology biobank for reliable basic/translational research and precision medicine.

Research biobanks are non-profit structures that collect, manipulate, store, analyze and distribute systematically organized biological samples and data for research and development purposes. Over the recent years, we have established a biobank, the Rheumatology BioBank (RheumaBank) headed by the Medicine and Rheumatology unit of the IRCCS Istituto Ortopedico Rizzoli (IOR) in Bologna, Italy for the purpose of collecting, processing, storing, and distributing biological samples and associated data obtained from patients suffering from inflammatory joint diseases. RheumaBank is a research biobank, and its main objective is to promote large-scale, high-quality basic, translational, and clinical research studies that can help elucidate pathogenetic mechanisms and improve personalization of treatment choice in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritides (SpA).

Efficacy, safety and tolerability of very low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study.

Introduction: Obesity can worsen fibromyalgia (FM) and very low-calorie ketogenic diet (VLCKD) is a potential therapeutic option for diseases that share clinical and pathophysiological features with FM. In this pilot interventional study, we investigated the effects of VLCKD in obese women with FM. Methods: Female patients with FM and a body mass index (BMI) ≥ 30 kg/m2 were eligible for VLCKD. The ketogenic phase (T0 to T8) was followed by progressive reintroduction of carbohydrates (T8 to T20). Changes in BMI, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), EuroQol 5D (EQ-5D) and 36-item Short Form Health Survey (SF-36) were evaluated. A change of 14% in FIQ was considered clinically relevant. The longitudinal association between BMI and patient-reported outcomes (PROs) was assessed using generalized estimating equations. Results: Twenty women were enrolled. Two discontinued the intervention. The mean age of the 18 patients who reached T20 was 51.3 years and mean BMI was 37.2 kg/m2. All patients lost weight during the first period of VLCKD and this achievement was maintained at T20. Mean BMI decreased from 37.2 kg/m2 at T0 to 34.8 kg/m2 at T4, 33.5 kg/m2 at T8 and 32.1 kg/m2 at T20 (p < 0.001). A significant reduction of mean FIQ from 61.7 at T0 to 37.0 at T4 and to 38.7 at T8 (p < 0.001) was observed and it was maintained at T20 with a mean FIQ of 39.1 (p = 0.002). Similar results were obtained for HADS, EQ-5D and SF-36. Analysing each participant, the reduction of FIQ was clinically meaningful in 16 patients (89%) at T4, in 13 (72%) at T8 and in 14 (78%) at T20. No significant association was observed between change in BMI and improvement of the PROs over time. Adverse effects were mild and transient. No major safety concerns emerged. Conclusion: These are the first data on the efficacy of VLCKD in FM. All patients achieved improvement in different domains of the disease, which was maintained also after carbohydrate reintroduction. Our results suggest that ketosis might exert beneficial effects in FM beyond the rapid weight loss. Clinical trial registration: This trial is registered on ClinicalTrials.gov, number NCT05848544.

Post-Acute COVID-19 Joint Pain and New Onset of Rheumatic Musculoskeletal Diseases: A Systematic Review.

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases.

mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models.

Initially introduced in therapy as immunosuppressants, the selective inhibitors of mTORC1 have been approved for the treatment of solid tumors. Novel non-selective inhibitors of mTOR are currently under preclinical and clinical developments in oncology, attempting to overcome some limitations associated with selective inhibitors, such as the development of tumor resistance. Looking at the possible clinical exploitation in the treatment of glioblastoma multiforme, in this study we used the human glioblastoma cell lines U87MG, T98G and microglia (CHME-5) to compare the effects of a non-selective mTOR inhibitor, sapanisertib, with those of rapamycin in a large array of experimental paradigms, including (i) the expression of factors involved in the mTOR signaling cascade, (ii) cell viability and mortality, (iii) cell migration and autophagy, and (iv) the profile of activation in tumor-associated microglia. We could distinguish between effects of the two compounds that were overlapping or similar, although with differences in potency and or/time-course, and effects that were diverging or even opposite. Among the latter, especially relevant is the difference in the profile of microglia activation, with rapamycin being an overall inhibitor of microglia activation, whereas sapanisertib was found to induce an M2-profile, which is usually associated with poor clinical outcomes.

Emil Zuckerkandl and his Dental Tubercle (Historical Note).

One of the eponyms most frequently cited in dental morphology texts, together with the Carabelli tubercle of the first permanent maxillary molars, is the Zuckerkandl tubercle of deciduous molars. However, references about Emil Zuckerkandl in the field of dental history and this particular entity are scarce. The reason this dental eponym was pushed "into the shadows" probably lies in the many other anatomical parts (including another tubercle, the pyramidal one of the thyroids), which took their names from this great anatomist.

The Extracellular Matrix in Glioblastomas: A Glance at Its Structural Modifications in Shaping the Tumoral Microenvironment-A Systematic Review.

BACKGROUND AND AIM: While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM's role in shaping tumoral development. METHODS: An online literature search was launched on PubMed/Medline and Scopus using the research string "((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))", and a systematic review was conducted in accordance with the PRISMA-P guidelines. RESULTS: The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns. CONCLUSIONS: Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.

Influence of Coaching on Effectiveness, Participation, and Safety of an Exercise Program for Postmenopausal Women with Osteoporosis: A Randomized Trial.

Purpose: We compared two different strategies providing professional coaching to administer an exercise program for women with postmenopausal osteoporosis (POP): individual training (IT) at home with trainer's supervision provided by telephone contacts at regular time-intervals or group training (GT) with trainer's live supervision. Our working hypothesis was that IT is a valid alternative to GT when GT is not feasible. Patients and Methods: This was a single-blind, randomized study. We recruited 52 women with POP, without significant comorbidity, and no participation in any structured exercise program within the previous 6 months. They were assigned randomly to IT or GT groups (n = 26 each). Distribution of age (IT: 68±4, GT: 67±8 years) and body mass index (IT: 23.0±2.5, GT: 21.4±5.1) was similar between groups. Each group performed the exercise program in two 1-hour sessions per week for 18 months. Primary outcome measure was Health-Related Quality of Life (HRQoL), as measured by the Short Osteoporosis Quality of Life Questionnaire. Secondary outcome measures focused on domains acknowledged to influence HRQoL (disability, fear of falling, weekly physical activity, physical function) or the effectiveness of the exercise program (retention, adherence, and safety). Significance level was set at p < 0.05. Results: No significant differences were observed between IT and GT groups for any domain. Retention, adherence, and safety were also similar. HRQoL, disability and fear of falling did not change between baseline and follow-up for either group. However, for both groups, physical function (knee flexion, shoulder mobility) and functional capacity (6-minute walking test) improved. Weekly physical activity levels increased from moderate range at baseline to intense at final assessment for both groups. Conclusion: IT and GT supervised exercise programs for women with POP provide similar effectiveness, participation and safety. Hence, both modalities should be considered for future translation in clinical practice of exercise recommendations for POP.

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Spine Fragility Fracture Prediction Using TBS and BMD in Postmenopausal Women: A Bayesian Approach.

The trabecular bone score (TBS) estimates bone microarchitecture and can be used to evaluate the risk of osteoporotic fractures independently of bone mineral density (BMD). In this retrospective case-control study, we tested and compared the ability of TBS and lumbar spine BMD (LS-BMD) to predict vertebral fragility fractures. The inclusion criteria were female sex, age range 50-90 years, menopause, and clinical risk factors for osteoporosis. Patients with secondary osteoporosis were excluded. LS-BMD and TBS were measured at the L1-L4 vertebral level. The ability of the two diagnostic systems in predicting vertebral fragility fractures was assessed by combining LS-BMD and TBS according to the Bayesian "OR rule" (the diagnosis is negative only for those negative for both tests, and it is positive for those who were positive for at least one test) or to the "AND rule" (the diagnosis is positive only for those positive to both tests and is negative for those negative for at least one test). Of the 992 postmenopausal women included, 86 had a documented vertebral fragility fracture. At the cutoff value used in the present study, the TBS and LS-BMD showed a similar diagnostic ability to predict vertebral fragility fractures, having positive predictive values (PPV) of, respectively, 13.19% and 13.24%. Negative predictive values (NPV) were, respectively, 95.40% and 94.95%. Compared to that of each single diagnostic system, the "OR-rule" significantly increased the NPV to 97.89%, while no statistically significant differences were found by using the "AND-rule". In conclusion, the present study highlights the possibility that combining LS-BMD and TBS could improve their predictive ability in diagnosing vertebral fragility fractures, and that there is a significant probability of absence of fractures in women who test negative to both diagnostic systems.

The effects of painless nerve growth factor on human microglia polarization.

Previous studies in the rat suggest that microglial cells represent a potential druggable target for nerve growth factor (NGF) in the brain. The painless human Nerve Growth Factor (hNGFp) is a recombinant mutated form of human nerve growth factor (hNGF) that shows identical neurotrophic and neuroprotective properties of wild-type NGF but displays at least 10-fold lower algogenic activity. From the pharmacological point of view, hNGFp is a biased tropomyosin receptor kinase A (TrkA) agonist and displays a significantly lower affinity for the p75 neurotrophin receptor (p75NTR). This study aimed to evaluate the expression of TrkA and p75NTR NGF receptors in two different human microglia cell lines, and to investigate the effects of hNGFp and wild-type NGF (NGF) on L-arginine metabolism, taken as a marker of microglia polarization. Both NGF receptors are expressed in human microglia cell lines and are effective in transducing signals triggered by NGF and hNGFp. The latter and, to a lesser extent, NGF inhibit cytokine-stimulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in these cells. Conversely NGF but not hNGFp stimulates arginase-mediated urea production.

Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a 'Seed-and Soil' Approach: A Systematic Review.

Background and aim: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Methods: An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. Results: The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Conclusions: Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.

The effects of CHF6467, a new mutated form of NGF, on cell models of human glioblastoma. A comparison with wild-type NGF.

CHF6467 is a mutated form of human recombinant nerve growth factor (NGF). The mutation selectively disrupts the binding of NGF to its p75NTR receptor while maintaining the affinity toward TrkA receptor. Because of such different profile of receptor interaction, CHF6467 maintains unaltered the neurotrophic and neuroprotective properties of wild-type NGF but shows reduced algogenic activity.In this study, we investigated the effects of CHF6467 on mortality, proliferation, cell-damage and migration in three human glioblastoma cell lines (U87MG, T98G, LN18), and in the rat astrocytoma C6 cells. Both CHF6467 and wild-type NGF, given in the range 1-50 ng/ml, did not modify cell proliferation, metabolism and migration, as well as the number of live/dead cells.The present in vitro data are predictive of a lack of tumorigenic activity by both wild-type NGF and CHF6467 on these cell types in vivo, and warrant for CHF6467 further clinical development.

Prevalence of Type 2 and Type 1 Diabetes in Psoriatic Arthritis: An Italian Study.

OBJECTIVE: Psoriatic arthritis (PsA) is burdened by an increased susceptibility to cardiovascular diseases. Comorbid diabetes may represent one of the key factors contributing to this risk. The aim of our medical records review study was to investigate the prevalence of type 2 diabetes (T2D) and type 1 diabetes (T1D) in an Italian PsA cohort. METHODS: The clinical records of all patients consecutively seen at our clinic with a diagnosis of PsA during a 12-month period were reviewed to identify comorbid T2D or T1D. For comparison, a 1:1 age- and sex-matched group of individuals with noninflammatory diseases was recruited. RESULTS: The final study cohort comprised 408 patients. The prevalence of T2D was 7.8% (95% confidence interval, 5.6-10.8) in PsA and 4.4% in controls (95% confidence interval, 2.8-6.9; p = 0.04). Two cases (0.49%) of T1D were identified in the PsA cohort, whereas no cases were observed in controls. In a multivariate logistic regression model including age, disease duration, and body mass index (BMI) as covariates, increasing age (odds ratio [OR], 1.079; p = 0.006) and BMI (OR, 1.188; p = 0.011) but not PsA duration predicted being classified as having T2D. In a similar model accounting for age and BMI, average disease activity score including 28 joints and C-reactive protein showed a trend toward significance (OR, 1.639; p = 0.066). CONCLUSIONS: In conclusion, our data provide further support to the emerging evidence of an increased risk of T2D in PsA patients. Cardiometabolic comorbidity represents a significant aspect of integrated arthritis management to improve long-term cardiovascular outcomes and to provide a comprehensive treatment.

Monoclonal Antibodies to CTLA-4 with Focus on Ipilimumab.

The immune checkpoint cytotoxic T lymphocyte-associated antigen 4 (CTLA-4 or CD152) is a negative regulator of T-cell-mediated immune responses which plays a critical role in suppressing autoimmunity and maintaining immune homeostasis. Because of its inhibitory activity on T cells, CTLA-4 has been investigated as a drug target to induce immunostimulation, blocking the interaction with its ligands. The antitumor effects mediated by CTLA-4 blockade have been attributed to a sustained active immune response against cancer cells, due to the release of a brake on T cell activation. Ipilimumab (Yervoy, Bristol-Myers Squibb) is a fully human anti-CTLA-4 IgG1κ monoclonal antibody (mAb) that represents the first immune checkpoint inhibitor approved as monotherapy by FDA and EMA in 2011 for the treatment of unresectable/metastatic melanoma. In 2015, FDA also granted approval to ipilimumab monotherapy as adjuvant treatment of stage III melanoma to reduce the risk of tumour recurrence. The subsequent approved indications of ipilimumab for metastatic melanoma, regardless of BRAF mutational status, and other advanced/metastatic solid tumours always involve its use in association with the anti-programmed cell death protein 1 (PD-1) mAb nivolumab. Currently, ipilimumab is evaluated in ongoing clinical trials for refractory/advanced solid tumours mainly in combination with additional immunostimulating agents.

Clinical experience with CTLA-4 blockade for cancer immunotherapy: From the monospecific monoclonal antibody ipilimumab to probodies and bispecific molecules targeting the tumor microenvironment.

The immune checkpoint cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an inhibitory regulator of T-cell mediated responses that has been investigated as target of monoclonal antibodies (mAbs) for cancer immunotherapy. The anti-CTLA-4 mAb ipilimumab represents the first immune checkpoint inhibitor that significantly improved overall survival in patients with unresectable/metastatic melanoma. The subsequent approved indications (often in the first-line setting) for melanoma and other advanced/metastatic solid tumors always require ipilimumab combination with nivolumab, an anti-programmed cell death protein 1 (PD-1) mAb. However, the improved clinical efficacy of the mAb combination is associated with increased immune-related adverse events, which might require treatment discontinuation even in responding patients. This drawback is expected to be overcome by the recent development of anti-CTLA-4 probodies proteolitycally activated in the tumor microenvironment and bispecific molecules targeting both CTLA-4 and PD-1, whose co-expression is characteristic of tumor-infiltrating T cells. These molecules would preferentially stimulate immune responses against the tumor, reducing toxicity toward normal tissues.

Osteitis condensans ilii: prevalence and characteristics of a neglected mimic of sacroiliitis.

OBJECTIVES: Osteitis condensans ilii (OCI) is a benign condition characterised by triangular sclerosis of the iliac bone which may mimic radiographic sacroiliitis. Prevalence is estimated between 0.9 and 2.5%, with female predominance, but the most recent article reporting original epidemiological data in the general population was published in 1971. The aim of our study is to contribute updated figures about prevalence of OCI in Italy. METHOD: A retrospective review of pelvic radiographs was conducted. Consecutive patients visiting the emergency department of our Institution between 1st January and 31st December 2020 were enrolled. Individuals with a past diagnosis of axial spondyloarthritis were excluded. Presence of OCI was evaluated by two musculoskeletal radiologists. Clinical and radiologic features such as osteoarthritis and insertional enthesopathy were also assessed. RESULTS: We included 1047 individuals (61% female) with a median age of 74 years. OCI was present in 10 cases, accounting for a prevalence in the general population of 1.0% (95% CI 0.5-1.7). All patients with OCI were women and, in the female sample, prevalence was 1.6% (95% CI 0.7-2.8). Clinical characteristics and associated radiographic features were not different between patients with OCI and women without OCI. CONCLUSIONS: The prevalence of OCI observed in our study is consistent with previous literature, and we confirm that it is more frequently retrieved in women. Longitudinal research is warranted to elucidate the evolution, while knowledge about the disorder is needed to raise the awareness of rheumatologists and radiologists and to properly identify and report the condition. Key Points • OCI may mimic sacroiliitis and is a major differential diagnosis of radiographic axial spondyloarthritis. • Prevalence of OCI in our sample is 1.0%, in line with previous literature. • OCI predominantly affects women, and our study suggests that the disorder can be incidentally identified even after childbearing age. • Increased awareness of the characteristics of OCI can facilitate identification and reporting of the disorder.

The Effect of Ketogenic Diet on Inflammatory Arthritis and Cardiovascular Health in Rheumatic Conditions: A Mini Review.

The principle of ketogenic diet (KD) is restriction of carbohydrates to a maximum of 5-10% of the total daily caloric intake, aiming at shifting body metabolism toward ketone bodies. Different studies suggested promising results of KD to help patients to lose weight, to reduce insulin requirements in diabetes, to supplement cancer protocols, to treat neurological conditions and to optimize control of metabolic and cardiovascular diseases. However, literature about the anti-inflammatory properties of KD in rheumatic diseases is still limited. The beneficial effects of weight loss in patients with inflammatory arthritis can be explained by biomechanical and biochemical factors. Obesity is associated with macrophage activation and production of pro-inflammatory cytokines including TNF-α, IL-1b, and IL-6. The clinical effect of KD may be primarily attributed to improvement of insulin sensitivity. Insulin resistance is associated with an increase of TNF-α, IL-1α, IL-1ß, IL-6, and leptin. Moreover, reduction of body's adipose tissue and weight loss account for part of the anti-inflammatory effects and for the impact of KD on cardiovascular health. In rheumatoid arthritis, fasting was shown to be effective in reducing disease symptoms, possibly through the production of ß-hydroxybutyrate (BHB), the main ketone body. BHB may exert inhibitory effects also on IL-17 and intermittent fasting improved the clinical manifestations of psoriatic arthritis. In ankylosing spondylitis, current literature doesn't allow to draw conclusion about the effects of KD. Future prospective studies will be needed to elucidate the potential beneficial effects of KD on specific domains and clinical outcomes in patients with inflammatory arthritis.

Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.

OBJECTIVE: Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19. METHODS: Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey. RESULTS: A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents. CONCLUSION: Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.