Dickkopf-Related Protein 1 (DKK-1) as a Possible Link between Bone Erosions and Increased Carotid Intima-Media Thickness in Psoriatic Arthritis: An Ultrasound Study.

Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by its complex clinical expression. We enrolled patients who met the ClASsification for Psoriatic Arthritis (CASPAR) criteria for PsA (n = 17), and healthy controls (n = 13). The lipid profile, C-reactive protein (CRP) and Dickkopf-related protein 1 (DKK-1) circulating levels were measured for all subjects. For the patients with PsA, (1) the erosive character of the articular disease was assessed by a musculoskeletal ultrasound and (2) the cardiovascular risk was evaluated using the Systematic Coronary Risk Evaluation (SCORE) chart and the ultrasound measurement of the carotid intima-media thickness. A higher titer of serum DKK-1 was associated with the presence of erosions (p < 0.005) and the cIMT correlated with DKK-1 levels in patients with PsA (r = 0.6356, p = 0.0061). Additionally, we observed a positive correlation between increased cIMT and CRP (r = 0.5186, p = 0.0329). Our results suggest that DKK-1 could be used as an early biomarker for the erosive character of the articular disease and for the assessment of the cardiovascular risk in PsA patients.

Preliminary Study on the Antioxidant Effect of Natural Based Products with Potential Application in Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a complex condition characterized by chronic pain and various sensory, motor, and autonomic symptoms. It involves a complex interplay of mechanisms in the nervous system, including neuroinflammation, sensitization of pain pathways, and dysfunction of the sympathetic nervous system. Antioxidants may play a role in CRPS by helping to counteract oxidative stress, which is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defences. CRPS involves inflammation and tissue damage, which can lead to increased ROS production and oxidative stress. Our paper represents a preliminary study on various commercially available natural-based products regarding their antioxidant effect. Several natural products with antioxidant properties, such as vitamins C and E, polyphenols, flavonoids, and botanical extracts, have shown promise in preclinical studies for their potential to alleviate pain and reduce inflammation associated with CRPS. The potential use of natural-based products with antioxidant effects for mitigating CRPS symptoms is still an area of ongoing research and investigation, but nonetheless it holds promise.

Outcomes of Prospectively Followed Pregnancies in Rheumatoid Arthritis: A Multicenter Study from Romania.

Women with rheumatoid arthritis (RA) may carry an increased risk of adverse pregnancy outcomes (APO). The aims of this study were to compare pregnancy outcomes in RA patients as compared to the general obstetric population (GOP) and to identify a risk profile in RA. A case-control study was conducted on 82 prospectively followed pregnancies in RA and 299 pregnancies from the GOP. The mean age at conception was 31.50 ± 4.5 years, with a mean disease duration of 8.96 ± 6.3 years. The frequency of APO in RA patients was 41.5%, 18.3% experienced spontaneous abortions, 11.0% underwent preterm deliveries, 7.3% had small for gestational age infants, 4.9% experienced intrauterine growth restriction, 1.2% experienced stillbirth, and 1.2% suffered from eclampsia. The risk of APO was correlated with a maternal age higher than 35 years (p = 0.028, OR = 5.59). The rate of planned pregnancies was 76.8%, and the subfertility rate was 4.9%. Disease activity improved every trimester, and approximately 20% experienced an improvement in the second trimester. Planned pregnancies and corticosteroids use (≤10 mg daily) were protective factors for APO in RA pregnancies (p < 0.001, OR = 0.12, p = 0.016, OR = 0.19, respectively). There was no significant association between APO and disease activity or DMARDs used before and during pregnancy. Regarding the comparison between the RA group and the controls, RA mothers were significantly older (p = 0.001), had shorter pregnancies (p < 0.001), and had neonates with a lower birth weight (p < 0.001).

Computer-Aided Diagnosis of Pulmonary Nodules in Rheumatoid Arthritis.

(1) Background: Rheumatoid arthritis (RA) is considered a systemic inflammatory pathology characterized by symmetric polyarthritis associated with extra-articular manifestations, such as lung disease. The purpose of the present study is to use CAD in the detection of rheumatoid pulmonary nodules. In addition, we aim to identify the characteristics and associations between clinical, laboratory and imaging data in patients with rheumatoid arthritis and lung nodules. (2) Methods: The study included a number of 42 patients diagnosed with rheumatoid arthritis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, examined from January 2017 to November 2022 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. Medical records were reviewed. A retrospective blinded review of CT for biopsy-proven pulmonary nodules in RA using Veolity LungCAD software was performed (MeVis Medical Solutions AG, Bremen, Germany). Imaging was also reviewed by a senior radiologist. (3) Results: The interobserver agreement proved to be moderate (κ = 0.478) for the overall examined cases. CAD interpretation resulted in false positive results in the case of 12 lung nodules, whereas false negative results were reported in the case of 8 lung nodules. The mean time it took for the detection of lung nodules using CAD was 4.2 min per patient, whereas the detection of lung nodules by the radiologist was 8.1 min per patient. This resulted in a faster interpretation of lung CT scans, almost reducing the detection time by half (p < 0.001). (4) Conclusions: The CAD software is useful in identifying lung nodules, in shortening the interpretation time of the CT examination and also in aiding the radiologist in better assessing all the pulmonary lung nodules. However, the CAD software cannot replace the human eye yet due to the relative high rate of false positive and false negative results.

Colchicine versus Physical Therapy in Knee Osteoarthritis.

Background: The treatment of osteoarthritis remains a major challenge due to the unavailability of a disease-modifying medication and the limitations of current therapeutic perspectives, which mainly target the symptoms, not the disease itself. The purpose of our study is to compare the efficacy of colchicine treatment versus physical therapy. Methods: The study included 62 patients diagnosed with knee osteoarthritis (KOA) according to the American College of Rheumatology (ACR) criteria, hospitalized within the time frame of October 2020−March 2022 in the Department of Rehabilitation Medicine and Physical Therapy of the Emergency Clinical County Hospital of Craiova. The participants were randomly divided into two groups. The observation period was 16 weeks long. The first group (31 patients) received colchicine at a dosage of 1 mg/day together with analgesics (acetaminophen < 2 g/day), while the second group (31 patients) received analgesics (acetaminophen < 2 g/day) together with a 16-week plan of physiotherapy. Results: Group II, in which patients underwent physical therapy, demonstrated a statistically significant decrease in both left (p < 0.001) and right (p = 0.012) knee VAS and WOMAC (p = 0.038) scores at 16 weeks, compared to the group treated with colchicine. Regarding the MSUS examination at 16 weeks, there were no significant changes in the structural abnormalities and no improvement in cartilage aspect or thickness. Higher BMI was associated with higher WOMAC score (p = 0.012), but not with higher VAS score (p = 0.062). Cholesterol and triglyceride levels were associated with high WOMAC (p < 0.001; p = 0.021) and high VAS (p = 0.023; p < 0.001) scores. Conclusions: Our study monitored VAS and WOMAC scores in two groups of patients with KOA, showing that physical therapy is more effective than colchicine in reducing symptoms. We found no statistically significant difference in musculoskeletal ultrasound (MSUS) feature improvement during the 16-week study.

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease-A Narrative Review.

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10-60% of patients with this disease. In this review, we aim to discuss the patterns of RA interstitial lung disease (ILD), the molecular mechanisms involved in the pathogenesis of ILD in RA, and also the therapeutic challenges in this particular extra-articular manifestation. The pathophysiology of RA-ILD has been linked to biomarkers such as anti-citrullinated protein antibodies (ACPAs), MUC5B mutation, Krebs von den Lungen 6 (KL-6), and other environmental factors such as smoking. Patients at the highest risk for RA-ILD and those most likely to advance will be identified using biomarkers. The hope is that finding biomarkers with good performance characteristics would help researchers better understand the pathophysiology of RA-ILD and, in turn, lead to the development of tailored therapeutics for this severe RA manifestation.

Interobserver Reliability of Magnetic Resonance Imaging of Sacroiliac Joints in Axial Spondyloarthritis.

INTRODUCTION: Axial spondyloarthritis (axSpA) is characterized by damage to the axial skeleton and entheses, and is often associated with extra-articular manifestations, in the presence of the human leukocyte antigen (HLA) B27. The aim of our study is to assess the performance of rheumatologists in interpreting the inflammatory and structural damage to sacroiliac joints, in comparison to radiologists. MATERIAL AND METHODS: The present study included a total of 34 patients diagnosed with axSpA, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA, examined from January 2021 to November 2021 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. All patients underwent physical examination, laboratory tests, and magnetic resonance imaging (MRI) of the sacroiliac joints. The images were interpreted by a senior radiologist (SR), a junior radiologist (JR), a senior rheumatologist (SRh), and a junior rheumatologist (JRh), who were blinded to the clinical and paraclinical data. RESULTS: The overall κ was 0.7 for the JR (substantial agreement), 0.707 for the SRh (substantial agreement), and 0.601 for the JRh (moderate agreement), in comparison with the SR. Regarding the overall inflammatory changes, the SRh and JR were proven to have substantial agreement (κ = 0.708 and 0.742, respectively) with the SR, while the JRh was proven to have moderate agreement (κ = 0.607). The structural damage observed by the JR showed substantial agreement (κ = 0.676) with the SR, while the SRh and JRh had substantial and moderate agreement (κ = 0.705 and 0.596, respectively) with the SR. CONCLUSIONS: Our study showed substantial agreement between the senior radiologist, senior rheumatologist, and junior radiologist, and moderate agreement with the junior rheumatologist.

COVID-19-A Trigger Factor for Severe Immune-Mediated Thrombocytopenia in Active Rheumatoid Arthritis.

Thrombocytopenia is defined as a platelet count below 150,000/mm3 for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm3 to 150,000/mm3 should be classified as having genuine thrombocytopenia or borderline thrombocytopenia. Thrombocytopenia is considered mild when the platelet count is between 70,000 and 150,000/mm3 and severe if the count is less than 20,000/mm3. Thrombocytopenia in rheumatoid arthritis is a rare complication, with an incidence estimated between 3 and 10%. The main etiological aspects include drug-induced thrombocytopenia and immune thrombocytopenic purpura. The most common hematological abnormalities in SARS-CoV-2 infection are lymphopenia and thrombocytopenia. It has been observed that the severity of thrombocytopenia correlates with the severity of the infection, being a poor prognosis indicator and a risk factor for mortality. COVID-19 can stimulate the immune system to destroy platelets by increasing the production of autoantibodies and immune complexes. Autoimmunity induced by viral infections can be related to molecular mimicry, cryptic antigen expression and also spreading of the epitope. During the COVID-19 pandemic, it is of great importance to include the SARS-CoV-2 infection in differential diagnoses, due to the increased variability in forms of presentation of this pathology. In this review, our aim is to present one of the most recently discovered causes of thrombocytopenia, which is the SARS-CoV-2 infection and the therapeutic challenges it poses in association with an autoimmune disease such as rheumatoid arthritis.

Non-alcoholic fatty liver disease and hematologic manifestations (Review).

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, and it is associated with numerous extra-hepatic manifestations or additional co-occurring diseases. The aim of the present review was the identification and management of the hematologic manifestations of NAFLD. One of the triggers is considered to be iron abnormalities. Increased ferritin levels, hepatic iron deposits and iron overload are associated with NAFLD. The iron overload degree and severity are associated with the level of liver fibrosis and with the risk for hepatocellular carcinoma. Excess iron deposits refers to the dysmetabolic iron overload syndrome (DIOS) and it is characterized by steatosis associated with moderate tissue iron deposition and increased levels of serum ferritin, while the serum transferrin saturation was normal. Further prospective studies are necessary to determine whether NAFLD has an independent risk for hematologic symptoms, besides the known risk factors. Future studies are also needed in order to assess the increasing impact of NAFLD on the micro- and macro-vascular complications of this systemic disease.

Rheumatic Immune-Related Adverse Events-A Consequence of Immune Checkpoint Inhibitor Therapy.

The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells' ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.

The Role of Clinical and Ultrasound Enthesitis Scores in Ankylosing Spondylitis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease, part of the spondyloarthritis (SpA) group, characterized by axial (spine and sacroiliac joints), entheseal, and peripheral joint involvement, which is frequently associated with extra-articular manifestations. MATERIAL AND METHODS: The study included a number of 30 patients diagnosed with AS according to the New York modified criteria, with history of entheseal pain, hospitalized between 2016-2018 in the Department of Rheumatology of the Emergency County Hospital of Craiova. RESULTS: Regarding the Belgrade Ultrasound Enthesitis Score (BUSES) score and the disease activity calculated using the Ankylosing Spondylitis Disease Activity Score (ASDAS), they did not show a statistically significant association (p = 0.738). Additionally, BUSES did not have a statistically significant association with the disease activity quantified by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (p = 0.094). The Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) clinical score was not statistically associated with ASDAS (p = 0.434) nor with BASDAI (p = 0.130). The SPARCC clinical score and the BUSES ultrasound score were statistically significantly associated, registering a value of p = 0.018. CONCLUSIONS: Our study proved a significant correlation between SPARCC and BUSES, although in literature the evidence is contrasting.

Musculoskeletal Ultrasound Diagnosis in Calcium Pyrophosphate Dihydrate Crystal Deposition Disease.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is extremely versatile. We present the case of a 52 years old patient referred for inflammatory pain of the left knee and ankle of recent onset with intense inflammatory syndrome that mimics rheumatoid arthritis. Musculoskeletal ultrasound was able to detect effusion, hyperechoic crystals within the cartilage and fibrocartilage, inside tendons, suggestive for CPPD disease and to guide fluid aspiration as well as in sustaining a rapid diagnosis corroborating images suggestive for CPPD disease to biological data - hypercalcemia and hyperparathyroidism in finding the predisposing condition, the parathyroid adenoma.