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Coatomer subunit α (COPA) syndrome is a mendelian autosomal dominant immune dysregulation disease characterized by early onset lung disease in the form of diffuse alveolar hemorrhaging or interstitial lung disease, frequently associated with arthritis, glomerulonephritis, and high titer autoantibodies usually mimicking other autoimmune diseases. While immunosuppressive medication has been effective in controlling arthritis, data on long-term lung disease control remains scarce, which poses a real challenge as the progression of lung disease is the main cause of poor life expectancy in COPA patients. Nevertheless, JAK inhibitor therapy seems to be the most promising therapeutic choice now.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (Ɛ R ) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of Ɛ R in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including Ɛ R measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for Ɛ R , and patients with Ɛ R ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with Ɛ R > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, Ɛ R was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). Ɛ R is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Objectives: The study has as main objective the evaluation of the potential roles of vitamin D, the neutrophil to lymphocyte ratio (NLR), and the systemic inflammation index (SII) as future biomarkers regarding the classification of flares in systemic lupus erythematosus (SLE)., Material and Methods: Individuals diagnosed with SLE were encompassed in this observational study. The current applicable criteria, namely The European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019 criteria had to be fulfilled. The participants underwent specific musculoskeletal examination, paraclinical investigations including complete blood count (CBC), determination of serum creatinine levels, as well as liver enzymes, and also the markers of inflammation. The fractions of the serum complement (C3 and C4) were also evaluated, together with serum vitamin D concentrations. Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) was required in order to analyze the research group's disease activity., Results: NLR and SII demonstrated validity, having statistically significant correlations with SELENA-SLEDAI (p value less than 0.001). The ROC analysis proved a strong discriminative power for NLR (AUC=0.96) and SII (AUC=0.963) in predicting severe disease flares. Optimal cut-off values were 3.45 for NLR and 877,002.19 for SII. Serum vitamin D concentrations had a weak association with the SLEDAI score (p=0.048, r=0.213)., Conclusions: NLR and SII can be considered reliable biomarkers for discriminating between the levels of disease activity in SLE individuals. Low serum levels of vitamin D may also influence disease severity, but require further validation., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022, Medical University Publishing House Craiova.)

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.

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., Competing Interests: None to declare, (Copyright © 2023, Medical University Publishing House Craiova.)

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).

(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.

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.

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.

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.

Thrombocytopenia is defined as a platelet count below 150,000/mm 3 for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm 3 to 150,000/mm 3 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/mm 3 and severe if the count is less than 20,000/mm 3 . 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 (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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Pădureanu et al.)

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.

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.

Introduction: Spondyloarthritis (SpA) is a group of chronic inflammatory disorders which includes ankylosing spondylitis (SA), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD) and undifferentiated spondyloarthritis (uSpA). The enthesis, the area of insertion of the tendon, ligament or joint capsule onto the bone, can be characterized as a central feature in PsA., Material and Methods: The study included a number of 28 patients, 18 females and 10 males, with PsA hospitalized during 2016-2018 in the Department of Rheumatology of the Emergency County Hospital of Craiova. All the patients were diagnosed with psoriatic arthritis according to CASPAR criteria and had a history of entheseal pain, mandatory criteria for inclusion in the study. All patients underwent clinical examination, laboratory tests and musculoskeletal ultrasonography (MSUS)., Results: The Belgrade Ultrasound Enthesitis Score (BUSES) was not significantly associated either with ESR (p=0.536) or CRP (p=0.965) values. Furthermore, the clinical evaluation through the LEEDS enthesitis index (LEI) showed no significant association with ESR (p=0.067) or CRP (p=0.206). Despite MSUS and clinical findings, there was no significant correlation between disease activity in psoriatic arthritis (DAPSA) and BUSES (p=0,549) or LEI (p=0,197). However, clinical and echographic scores (BUSES and LEI) were significantly associated (p=0.001)., Conclusions: Our study proved a significant correlation between LEI and BUSES, although in literature the evidence is contrasting. This is probably due to the fact that the majority of the patients had high disease activity which made the clinical assessment similar to the US. Further studies on more numerous groups of patients have to be conducted in order to debate the inconsistencies related to clinical and US examinations in patients with PsA.

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.