Quantitative reconstruction of Holocene ground displacements in the offshore part of the Campi Flegrei caldera (southern Italy): Perspectives from seismo-stratigraphic and archaeological data

Analysis of high-resolution seismic profiles integrated with archaeological data along the coast has allowed quantifying the last ~10 ka BP displacements in the offshore part of the Campi Flegrei resurgent caldera, one of the world’s highest-risk volcanic areas. Previous onland studies revealed that, following the Neapolitan Yellow Tuff (NYT) eruption at 15 ka, post-caldera evolution was associated with rapid ground uplift and subsidence cycles. In this paper, we use the stacking pattern of Prograding Wedges (PWs) and Aggrading Fills (AF) to reconstruct relative sea-level changes and estimate the amount of vertical deformation in the Pozzuoli Bay, the submerged part of the caldera. We document five generations of prograding wedges (PW1 to PW5), associated with as many periods of relative ground stability between uplift and subsidence. Instead, deposition of aggrading fills above prograding wedges underpins the subsidence that typically follows volcanic unrest and uplift. The older wedges PW1 and PW2 are larger and likely indicate whole-caldera uplift events. In particular, the development of PW2 starting from ~5.2 ka is related to the rapid growth of a resurgent dome in the central part of the caldera. After ~3.7 ka, subsidence prevailed in the caldera leading to deposition of an aggrading fill (AF2). However, subsidence was interrupted by short-term uplift episodes in historical times at (100 BCE-100 CE, 600–700 CE, 1430–1538 CE) that led to the growth of comparatively minor-sized wedges PW1 to PW3, respectively. Displacement of coastal infrastructures of the Roman age (~2 ka BP) is consistent with the vertical motion retrieved by the seismostratigraphic analysis, and further indicates the existence of two deformation signals. A short-wavelength signal confined to the Pozzuoli Bay reflects the contribution of an intra-caldera source. This signal is superposed to a long-wavelength regional subsidence increasing between Naples and Procida Island from 1.5 to 2 mm/a, respectively. The east-to-west enhancing subsidence likely reflects the transition between the uplifting Apennines and the foundered Tyrrhenian back-arc basin

Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs)

Background: Biological DMARDs (bDMARDs) have been proven to prevent joint damage and bone erosions. Nevertheless, approximately 15% of rheumatoid arthritis (RA) patients on bDMARDs will progress despite good control of joint inflammation. Objectives: The objective of our study is to investigate the factors associated with radiological progression of patients treated with bDMARDs. Design: We conducted a retrospective analysis of longitudinally collected data on RA patients starting bDMARDs. Methods: Presence or development of new erosions was assessed by a skilled rheumatologist at the time of the visit (baseline and 12 months thereafter). To determine the predictors of erosions, we employed multivariable logistic regression models. Discriminatory capacity for the prediction of new erosion development was assessed with receiver operating characteristic (ROC) curve, which was based on the logistic regression model. Results: A total of 578 RA patients starting bDMARDs were included in the study. Overall, 46 patients (approximately 10%) had radiographic progression (at least one new erosion) at 12 months of follow-up. The factors independently associated with higher risk of developing new erosions while on bDMARD were younger age, high disease activity at baseline, not being treated with cDMARDs, and presenting with erosions at baseline. In addition, we built a predictive model that can accurately foresee new erosions (AUC 0.846) in patients receiving bDMARDs. Conclusion: We found that baseline erosive disease, higher disease activity during treatment, younger age, and monotherapy were the factors independently associated with the development of bone erosions. Our study may inform future targeted intervention in RA patients at risk of radiographic progression

New strategies for the prevention and treatment of systemic and local bone loss; from pathophysiology to clinical application

Bone loss is the result of a negative unbalance between bone formation ad bone resorption. In the last years, the studies on the Wnt canonical pathway have highlighted its crucial role in bone balance through its influence on the activity and maturation of the osteoblast line and in the Receptor Activator of Nuclear Factor \u3ba B (RANK) - RANK ligand (RANKL)/Osteoprotegerin (OPG) system. These mechanisms are involved not only in the pathological processes inducing not only systemic bone loss (ie. Postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, etc.), but also at a local level, as happens in Rheumatoid Arthritis (RA). Recently, several new drugs for the treatment of bone loss have been approved, while some others are still under development. The most promising new drugs in the treatment of osteoporosis include the antibody that neutralizes RANKL (denosumab, DMAb), monoclonal antibodies against sclerostin and parathyroid hormone-related protein analogue. Other new strategies for the prevention and treatment of bone loss include calcilytics, cathepsin K inhibitor or the combination or the sequential use of the current drugs. New insights concerning the treatment of the local bone loss in RA and in Complex Regional Pain Syndrome type I are also provided in this review

Calcium and vitamin D supplementation: when and why

: Osteoporosis is a common disease, with fragility fractures representing its dreaded complications. The role of calcium and vitamin D supplementation needs to be addressed in the context of a heavy health burden, with a massive impact on individuals, healthcare systems, and societies as a whole. Calcium and vitamin D are often discussed together as interventions for promoting bone health. Still, it is essential to remember that they are quite distinct entities that play different roles in mineral metabolism. Insufficient calcium intake and vitamin D deficiency are common and widespread. Furthermore, a strong association between vitamin D deficiency and extra-skeletal outcomes has emerged over the last decades. When dietary intake is insufficient, with little room for improvement, several supplementation strategies have proved to be effective and safe. Adequate calcium intake and vitamin D serum levels should be pursued efficiently in the general population, and deficiency should be considered unacceptable in subsets particularly at risk. The aim of this narrative review was to present an overview of calcium and vitamin D intake and their supplementation

Gender disparity in authorship of guidelines and recommendations in rheumatology

Gender disparity in authorship of guidelines and recommendations in rheumatology

Electroencephalographic evaluation under standing sedation using sublingual detomidine hydrochloride in Egyptian Arabian foals for investigation of epilepsy

BackgroundA standardized protocol for electroencephalography (EEG) under standing sedation for the investigation of epilepsy in foals is needed.Hypothesis/objectivesTo evaluate a modified standardized EEG protocol under standing sedation using sublingual detomidine hydrochloride in Egyptian Arabian foals.AnimalsNineteen foals (controls, 9; juvenile idiopathic epilepsy [JIE], 10).MethodsDescriptive clinical study. Foals were classified as controls or epileptic based on history or witnessed seizures and neurological examination. Foals were sedated using sublingual detomidine hydrochloride at a dosage of 0.08 mg/kg to avoid stress associated with injectable sedation. Once foals appeared sedated with their heads low to the ground and with wide base stance (30 minutes), topical lidocaine hydrochloride was applied at the determined locations of EEG electrodes. Fifteen minutes were allowed for absorption and electrodes were placed, protected, and EEG recording performed.ResultsLevel of sedation was considered excellent with no need of redosing. The EEG recording lasted from 27 to 51 minutes and provided interpretable data. Epileptic discharges (ED) were noted predominantly in the central-parietal region in 9 of 10 epileptic foals. Photic stimulation triggered ED in 7 of 10 epileptic foals and in none of the controls. Foals were not oversedated and recovered uneventfully.Conclusions and clinical importanceSublingual detomidine hydrochloride is a safe, painless, simple, and effective method of sedation for EEG recording in foals. Sublingual sedation allowed the investigation of cerebral electrical activity during states of sleep and arousal, and during photic stimulation for the investigation of epilepsy in foals

Machine learning to characterize bone biomarkers profile in rheumatoid arthritis

BackgroundBone metabolism is disrupted in rheumatoid arthritis (RA); however, the bone metabolic signature of RA is poorly known. The objective of the study is to further characterize the bone metabolic profile of RA and compare it to psoriatic arthritis (PsA), systemic sclerosis (SSc) and healthy controls.MethodsWe did a cross-sectional case-control study on consecutively enrolled patients and age-matched controls. We collected clinical characteristics, serum biomarkers related to bone metabolism and Bone Mineral Density (BMD). A multiple correlation analysis using Spearman's rank correlation coefficient was conducted within the RA patient group to investigate associations between biomarker levels and clinical variables. Machine learning (ML) models and Principal Component Analysis (PCA) was performed to evaluate the ability of bone biomarker profiles to differentiate RA patients from controls.ResultsWe found significantly lower BMD in RA patients compared to PsA, and Systemic Sclerosis SSc groups. RA patients exhibited higher Dkk1, sclerostin and lower P1nP and B-ALP levels compared to controls. No significant differences in CTX levels were noted. Correlation analysis revealed associations between bone biomarkers and clinical variables. PCA and ML highlighted distinct biomarker patterns in RA which can effectively discriminated bone biomarkers profile in RA from controls.ConclusionOur study helped uncover the distinct bone profile in RA, including changes in bone density and unique biomarker patterns. These findings enhance our comprehension of the intricate links between inflammation, bone dynamics, and RA activity, offering potential insights for diagnostic and therapeutic advancements in managing bone involvement in this challenging condition

Tapering glucocorticoids and risk of flare in rheumatoid arthritis on biological disease-modifying antirheumatic drugs (bDMARDs)

Introduction: Glucocorticoids are still a mainstream of rheumatoid arthritis (RA) treatment. Reducing glucocorticoids should be attempted in all patients. However, choosing the right tapering strategy is challenging. The primary aim of our study is to determine the dose-response association between glucocorticoid tapering and risk of flare in RA. Methods: We conducted a case-crossover study to determine the factors associated to higher risk of flare in patients with RA. In case-crossover studies time-varying factors are assessed before events (hazard periods) and before control periods. We defined hazard periods as the 6 months immediately preceding flares of RA. Control periods were the 6 months prior to visits without flare. Exposure of interest was the tapering of glucocorticoids to various doses. Results: 508 patients with RA were included in the study and 267 (52.5%) had at least a flare and served as the case-crossover study population. 1545 visits were available for analysis and 345 (22.3%) flares were recorded. Discontinuation of glucocorticoids (ie, tapering to doses of 0 mg/day) and tapering to 0-2.5 mg/day was associated with higher risk of flare (adjusted OR (aOR) of 1.45, 95% CI: 1.13 to 2.24 and aOR of 1.37; 95% CI: 1.06 to 2.01, respectively). Tapering to doses >2.5 mg/day was not associated with significantly higher risk of flare. Conclusions: We found that tapering to doses of >2.5 mg/day was generally effective in terms of risk of flare. Flare risk was higher when glucocorticoids were tapered to doses ≤2.5 mg/day. Our study might help design new tapering strategies in patients with RA on biological disease-modifying antirheumatic drugs

Pharmacological treatment in adult patients with CRPS-I: A systematic review and meta-analysis of randomised controlled trials

Objective. Several pharmacological treatments have been proposed for the treatment of complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse the efficacy of the various pharmacological approaches in adults with CRPS-I.Methods. We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30 June 2021 to identify placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, CSs, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or IVIGs for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment.Results. We included 20 placebo-controlled or active-controlled RCTs (including a total of 818 adults with CRPS-I) that used bisphosphonates (n = 7), ketamine (n = 2), CSs (n = 2), anti-epileptics (n = 1), NSAIDs/selective inhibitors of cyclooxygenase-2 (COXIBs) (n = 2), scavengers/magnesium sulphate (n = 5), or IVIGs (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. Treatment with bisphosphonates showed a significant reduction in the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: -23.8, 95% CI: -28.0 to -19.6; I-2 = 36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS for pain (random effects WMD: -8.27, 95% CI: -12.9 to -3.70; I-2 = 0%). Treatment with other agents did not reduce the values of the VAS/NRS assessments of pain.Conclusion. This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I

Bone loss occurs in Inflammatory Rheumatic Musculoskeletal Diseases (iRMD) patients treated with low dose glucocorticoids, but is prevented by anti-osteoporosis medications

Background: The negative effects of glucocorticoids (GCs) on the bone depend on dose and treatment duration. However, it is unclear whether a safe dose exists, especially for patients with inflammatory rheumatic musculoskeletal diseases (iRMDs). Methods: We conducted a longitudinal cohort study on women with iRMD. Bone mineral density and fractures were assessed prospectively and compared to a matched cohort. Kaplan-Meier curves with log-rank test were made for iRMD (stratified for glucocorticoid use and dosage) and matched cohort respectively. Multivariable Cox regression survival models were also employed to analyze the effect of GCs on fracture. Results: 884 women with iRMD and 1,766 controls (age, T-score, and 10-year fracture risk matched) were included in the study and followed for up to 6 years. BMD levels decreased significantly in all GCs users not receiving anti-osteoporosis treatment (-4.26% p 0.0011, -4.23% p 0.0422, -2.66% p 0.0006 for ≥5 mg/day, 2.5 mg to 5 mg and 0 to 2.5 mg/day of prednisolone, respectively). Anti-osteoporotic treatment (largely bisphosphonates) prevented bone loss only in patients receiving less than 5 mg/day of prednisone. Fracture incidence was greater in patients with iRMD compared to controls but only GC doses above 5 mg/day were associated with significantly higher risk of fracture. Conclusion: GC doses as low as 2.5 mg/day were associated with BMD loss in iRMD but this effect was preventable. BMD loss in patients taking ≥5 mg/day was not totally prevented by anti-osteoporotic medications currently used in clinical practice, resulting in higher risk of fracture. This article is protected by copyright. All rights reserved