Symptomatic vertebral fractures are common among the population and are associated with pain and obstruction of free movement of the individual. Vertebroplasty is a minimally invasive, fluoroscopically guided medical procedure widely used to treat these vertebral fractures. It involves the percutaneous injection of bone cement, typically polymethyl methacrylate, into the fractured vertebra to provide stabilization, alleviate pain, and restore structural integrity. However, fluoroscopy for real-time image guidance exposes patients to low doses of ionizing radiation. This study aimed to assess the extent of DNA damage by quantifying DNA double-strand breaks (DSBs) in peripheral blood mononuclear cells following low-dose irradiation in patients undergoing vertebroplasty. Blood samples were collected before and after the medical procedure. DNA damage was detected in lymphocytes using immunofluorescence microscopy, assessing the co-localization of γ-H2AX and 53BP1 DNA damage-repair proteins as markers of DSBs. No patient received more than a 100 mGy cumulative air kerma dose during fluoroscopy time. In the investigated group of 67 patients, a statistically significant increase in DSBs’ frequency was observed after vertebroplasty (p < 0.001) and this increase was not correlated with an increase in the dose received by the patient. Our findings indicate a significant rise in DNA damage in patients following vertebroplasty, despite the low radiation doses received during this routine medical procedure.
BACKGROUND:Immune thrombocytopenia (ITP) is a disorder of increased platelet destruction and reduced platelet production and is associated with an increased bleeding risk and a compromised quality of life. Available therapies are ineffective in at least 20% of cases. Mezagitamab is an anti-CD38 antibody that targets plasma cells, plasmablasts, and natural killer cells. METHODS:We conducted this multicenter, double-blind, randomized, placebo-controlled trial to assess the safety and efficacy of mezagitamab at a dose of 100 mg, 300 mg, or 600 mg, as compared with placebo, administered subcutaneously once weekly for 8 weeks in adults with persistent or chronic ITP (mean platelet count on ≥2 measurements, <30,000 per microliter). The primary end point was adverse events. A key secondary efficacy end point was a platelet response (defined by a platelet count of ≥50,000 per microliter and ≥20,000 per microliter above the baseline value) on at least two visits at any time through week 16. RESULTS:In the combined mezagitamab groups (28 participants), the mean age was 50 years (range, 24 to 88) and the mean number of previous ITP therapies was 4 (range, 1 to 9); in the combined placebo groups (13 participants), the mean age was 39 years (range, 20 to 65) and the mean number of previous ITP therapies was 4 (range, 1 to 13). The mean baseline platelet count was 19,100 and 17,300 per microliter, respectively. Adverse events were reported in 19 of 28 participants (68%) in the combined mezagitamab groups and in 9 of 13 participants (69%) in the combined placebo groups; adverse events of grade 3 or higher in 5 of 28 participants (18%) and in 3 of 13 participants (23%), respectively; and serious adverse events in 4 of 28 participants (14%) and in 1 of 13 participants (8%). Through week 16, a platelet response was observed in 10 of 11 participants (91%) in the mezagitamab 600-mg group and in 3 of 13 participants (23%) in the combined placebo groups. CONCLUSIONS:Treatment with mezagitamab led to increased platelet counts, with a safety profile that appeared to be similar to that of placebo among participants with persistent or chronic ITP. (Funded by Takeda Development Center Americas; ClinicalTrials.gov number, NCT04278924.).
Nailfold capillaroscopy (NFC) is a well-established, highly specialized, non-invasive method for assessing microcirculation and represents the “gold standard” in rheumatology for distinguishing primary from secondary Raynaud’s phenomenon (RP). Through analysis of capillary structures in the nailfold region, clinicians can identify diff erent patterns (scleroderma, scleroderma-like, and non-specifi c). Despite its clinical signifi cance, image interpretation remains challenging due to subjectivity and the requirement for substantial examiner expertise. In recent years, artifi cial intelligence (AI) has off ered novel solutions through the automated recognition and analysis of capillary structures. Machine learning and deep learning approaches have demonstrated high eff ectiveness in detecting abnormalities, classifying capillary patterns, and predicting the risk of systemic sclerosis. Projects such as CAPI-Detect, along with various other machine learning, deep learning, and neural network models (DenseNet-121, Effi cientNet-B0, ResNet-34, NFC-Net), have shown that AI can identify novel quantitative parameters not accessible through traditional visual assessment and can increase the objectivity and reproducibility of results up to 90%. Most studies in this fi eld focus on capillaroscopic patterns in systemic sclerosis (SSc); however, pilot studies in juvenile dermatomyositis, diabetes mellitus, and hypertension further highlight the applicability of these technologies. Some AI models are even capable of distinguishing onychomycosis, nail psoriasis, and subungual melanoma. Machine learning and deep learning models based on image analysis (Vision Transformer, ViT) appear to represent an additional valid system for the early and rapid interpretation of NFC images and morphological biomarkers in systemic sclerosis (SSc), integrating EULAR-validated algorithms for distinguishing scleroderma from non-scleroderma patterns with artifi cial intelligence (AI). Beyond its diagnostic applications, AI also holds potential in disease monitoring, assessment of therapeutic response, and the development of personalized treatment strategies. The processing of digital images through validated machine learning algorithms, neural networks, and related approaches is aligned with the priorities of the National Health Strategy 2030 for digitalization and the development of eHealth (Policy 2.5). The establishment of a National Digital Platform for Medical Diagnostics is envisaged, aimed at supporting all medical specialties. This platform will be integrated with the National Health Information System and the electronic patient record, with the primary objective of improving the quality of healthcare services. The integration of AI into medical practice opens new opportunities to support early diagnosis and improved management of patients with microangiopathy, facilitating timely detection and the prevention of complications, with the ultimate aim of ensuring better quality of life and preserved functional capacity.
OBJECTIVES:A systematic literature review (SLR) of publications from 2000 to 2022 identified terminology for calcium pyrophosphate crystal deposition (CPPD) and revealed substantial heterogeneity and poor adherence to recommendations. This study aimed to standardise CPPD terminology by developing an international consensus on labels and definitions. METHODS:Members of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) were invited by email to participate in a 3-round Delphi exercise. A steering committee identified key components of CPPD aetiology, pathophysiology, and clinical presentation among elements appearing in >10% of SLR papers, adding or removing items when scientifically justified. Participants selected preferred labels for each element. Respondents to the first round were invited to subsequent rounds. This paper reports the resulting G-CAN CPPD nomenclature. RESULTS:Consensus was reached for 'calcium pyrophosphate (CPP) crystal' and 'calcium pyrophosphate crystal deposition (CPPD)' to describe the deposition process. The unified term 'calcium pyrophosphate crystal deposition on imaging' was adopted across imaging modalities, whereas 'chondrocalcinosis' was redefined as conventional radiographic cartilage calcification consistent with CPPD. Four clinical manifestations were identified: 'acute CPP crystal arthritis' (with 'flare' for acute episodes), 'chronic CPP crystal arthritis', 'crowned dens syndrome', and 'osteoarthritis with CPPD'; the term 'pseudogout' received no support. The condition is now classified as 'asymptomatic CPPD' or 'CPPD disease' for symptomatic presentations. CONCLUSIONS:This G-CAN nomenclature is the first systematic effort to align CPPD terminology with contemporary biological and imaging evidence. By resolving longstanding ambiguities-particularly regarding 'chondrocalcinosis'-it provides a framework for consistent research definitions, clinical trial homogeneity, and improved patient care.
BACKGROUND:Rezpegaldesleukin is an interleukin-2 receptor agonist that selectively expands and enhances the function of regulatory T cells (Tregs), offering a novel therapeutic approach for autoimmune and inflammatory diseases such as atopic dermatitis. We aimed to compare the efficacy and safety analyses of rezpegaldesleukin with placebo in adults with moderate-to-severe atopic dermatitis naive to biological treatments. METHODS:REZOLVE-AD was a phase 2b, randomised, double-blind, placebo-controlled study conducted in 107 community research centres or hospitals in ten countries (Australia, Bulgaria, Canada, Croatia, Czechia, Germany, Hungary, Poland, Spain, and the USA). Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria) diagnosed at least 12 months before enrolment, with moderate-to-severe disease activity defined by an Eczema Area and Severity Index (EASI) score of at least 16·0, validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of at least 3 (moderate), and at least 10% affected body surface area. Patients were randomly allocated (3:3:3:2) to receive subcutaneous rezpegaldesleukin 24 μg/kg or rezpegaldesleukin 18 μg/kg every 2 weeks, rezpegaldesleukin 24 μg/kg every 4 weeks, or placebo for 16 weeks during the induction period. Randomisation was done by an independent vendor using Randomisation and Trial Supply Management methodology via an interactive response system and was stratified by baseline disease severity (vIGA-AD 3 [moderate] vs 4 [severe]) and geographical region (North America vs rest of world). All patients, investigators, and those assessing outcomes were masked to treatment assignment. Outcomes for the induction period were assessed through week 16 and are included in this report. The primary endpoint was percentage change from baseline in EASI score at week 16. Efficacy and safety analyses were conducted in all randomly assigned patients exposed to study treatment, excluding those enrolled at two sites closed due to Good Clinical Practice non-compliance, both of which received notification of closure approximately 300 days before database lock. All missing data were imputed with multiple imputation. The trial was registered with ClinicalTrials.gov (NCT06136741). FINDINGS:398 patients were enrolled between Nov 15, 2023, and Jan 9, 2025. A total of 393 patients were analysed (104 in the rezpegaldesleukin 24 μg/kg every 2 weeks group, 106 in the rezpegaldesleukin 18 μg/kg every 2 weeks group, 110 in the rezpegaldesleukin 24 μg/kg every 4 weeks group, and 73 in the placebo group); 203 (52%) patients were female and 190 (48%) were male. All three rezpegaldesleukin groups met the primary endpoint. Rezpegaldesleukin showed dose-dependent improvements compared with placebo in mean percentage change in EASI from baseline at week 16: -61% (SE 3·8) for rezpegaldesleukin 24 μg/kg every 2 weeks, -58% (3·8) for rezpegaldesleukin 18 μg/kg every 2 weeks, and -53% (3·7) for rezpegaldesleukin 24 μg/kg every 4 weeks versus -31% (4·5) for placebo. Treatment differences versus placebo were -30 percentage points (95% CI -41·3 to -18·0; p<0·0001) for rezpegaldesleukin 24 μg/kg every 2 weeks, -27 percentage points (-38·5 to -15·7; p<0·0001) for rezpegaldesleukin 18 μg/kg every 2 weeks, and -22 percentage points (-33·3 to -10·3; p=0·0002) for rezpegaldesleukin 24 μg/kg every 4 weeks. Treatment-emergent adverse events observed in at least 5% of rezpegaldesleukin-treated patients (n=320) and greater than placebo (n=73) included injection-site reaction (223 [70%] vs three [4%]), eosinophilia (25 [8%] vs two [3%]), pyrexia (20 [6%] vs two [3%]), headache (20 [6%] vs three [4%]), upper respiratory tract infections (19 [6%] vs four [5%]), and arthralgia (16 [5%] vs one [1%]). Nearly all (>99%) injection-site reactions were mild to moderate in severity and resolved. There was no evidence of an increased risk of serious or severe adverse events, and no deaths were reported during the induction period. INTERPRETATION:Over the 16-week induction period, rezpegaldesleukin treatment resulted in significant and clinically meaningful improvements across multiple clinical endpoints, including the primary endpoint of EASI percentage change from baseline, in comparison with placebo. Rezpegaldesleukin had a clinically favourable adverse event profile in adult patients with moderate-to-severe atopic dermatitis, supporting its further development as a novel Treg-enhancing biological treatment. FUNDING:Nektar Therapeutics.
