Background: This study was designed to evaluate the relationship between serum interleukin-33 (IL-33) levels and clinical features of the disease in patients with Familial Mediterranean Fever (FMF).
Methods: Fifty-four patients diagnosed with FMF (28 colchicine responsive and 26 colchicine resistant) and 29 healthy controls constituted the study population. Demographic, clinical, biochemical and inflammatory parameters, as well as serum IL-33 levels of the participants, were compared.
Results: The mean age of FMF patients was 34.3 ± 9.8 years, and 54% were female. Colchicine-resistant patients exhibited significantly higher median CRP levels than both colchicine-responsive patients and healthy controls (median [IQR]: 16 [30.4] mg/L, 2.9 [3.4] mg/L, and 3.4 [2.8] mg/L, respectively; p < 0.001). Median serum IL-33 levels were higher in FMF patients than in controls (273 [387] ng/L vs. 221 [179] ng/L, p = 0.06). The colchicine-responsive group had significantly higher IL-33 levels compared to the control group (287 [495] ng/L vs. 221 [179] ng/L, p = 0.006), while no significant difference was observed between the colchicine-resistant group and controls (257 [219] ng/L vs. 221 [179] ng/L, p = 0.74). No significant correlations were identified between IL-33 levels and inflammatory markers or clinical characteristics.
Conclusions: Serum IL-33 levels do not seem to be associated with FMF disease activity; however, the observed increase in colchicine-responsive patients may indicate an immunomodulatory or compensatory function. Further comprehensive studies are needed to elucidate the role of IL-33 in FMF pathogenesis.
背景:本研究旨在评价家族性地中海热(FMF)患者血清白细胞介素-33 (IL-33)水平与疾病临床特征的关系。方法:54例确诊为FMF的患者(28例秋水仙碱应答,26例秋水仙碱耐药)和29例健康对照构成研究人群。比较参与者的人口学、临床、生化和炎症参数以及血清IL-33水平。结果:FMF患者平均年龄34.3±9.8岁,女性占54%。秋水仙碱耐药患者CRP水平中位数明显高于秋水仙碱应答患者和健康对照组(中位数[IQR]: 16 [30.4] mg/L, 2.9 [3.4] mg/L和3.4 [2.8]mg/L, p < 0.001)。FMF患者血清中位IL-33水平高于对照组(273 [387]ng/L vs. 221 [179] ng/L, p = 0.06)。秋水仙碱反应组IL-33水平明显高于对照组(287 [495]ng/L vs. 221 [179] ng/L, p = 0.006),而秋水仙碱耐药组与对照组无显著差异(257 [219]ng/L vs. 221 [179] ng/L, p = 0.74)。IL-33水平与炎症标志物或临床特征之间未发现显著相关性。结论:血清IL-33水平似乎与FMF疾病活动性无关;然而,观察到秋水仙碱反应患者的增加可能表明免疫调节或代偿功能。IL-33在FMF发病机制中的作用有待进一步深入研究。
{"title":"Assessment of Interleukin-33 Levels in Patients with Familial Mediterranean Fever.","authors":"Asil Demirezen, Aslihan Avanoğlu Güler, Hazan Karadeniz, Mustafa Kavutçu, Abdurrahman Tufan","doi":"10.2478/rjim-2026-0001","DOIUrl":"https://doi.org/10.2478/rjim-2026-0001","url":null,"abstract":"<p><strong>Background: </strong>This study was designed to evaluate the relationship between serum interleukin-33 (IL-33) levels and clinical features of the disease in patients with Familial Mediterranean Fever (FMF).</p><p><strong>Methods: </strong>Fifty-four patients diagnosed with FMF (28 colchicine responsive and 26 colchicine resistant) and 29 healthy controls constituted the study population. Demographic, clinical, biochemical and inflammatory parameters, as well as serum IL-33 levels of the participants, were compared.</p><p><strong>Results: </strong>The mean age of FMF patients was 34.3 ± 9.8 years, and 54% were female. Colchicine-resistant patients exhibited significantly higher median CRP levels than both colchicine-responsive patients and healthy controls (median [IQR]: 16 [30.4] mg/L, 2.9 [3.4] mg/L, and 3.4 [2.8] mg/L, respectively; p < 0.001). Median serum IL-33 levels were higher in FMF patients than in controls (273 [387] ng/L vs. 221 [179] ng/L, p = 0.06). The colchicine-responsive group had significantly higher IL-33 levels compared to the control group (287 [495] ng/L vs. 221 [179] ng/L, p = 0.006), while no significant difference was observed between the colchicine-resistant group and controls (257 [219] ng/L vs. 221 [179] ng/L, p = 0.74). No significant correlations were identified between IL-33 levels and inflammatory markers or clinical characteristics.</p><p><strong>Conclusions: </strong>Serum IL-33 levels do not seem to be associated with FMF disease activity; however, the observed increase in colchicine-responsive patients may indicate an immunomodulatory or compensatory function. Further comprehensive studies are needed to elucidate the role of IL-33 in FMF pathogenesis.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Urinary tract infections (UTIs) are associated with increased morbidity and mortality, yet data on the importance of secondary bacteremia remain scarce.
Methods: This retrospective, single-center study was conducted at a tertiary university hospital and included patients, hospitalized for UTIs, in order to assess the impact of secondary bacteremia on clinical outcomes (need for surgery, antibiotic change or death) and identify predictors for its presence.
Results: A total of 232 patients were included, with 56 (24.1%) developing secondary bacteremia. The bacteremia group exhibited higher CRP levels (18 mg/dL vs. 8 mg/dL, p < 0.01), lower hemoglobin (11.1 vs. 12 g/dL, p < 0.01), and higher disease severity scores. Hospital-acquired infections were an independent predictor of bacteremia (aOR: 4.440, p = 0.045). Patients with bacteremia exhibited longer hospital stays (8.5 vs. 4 days, p < 0.01) while its presence was independently associated with mortality (OR 11.01, 95% CI 1.19-101.50, p = 0.034)Multidrug-resistant (MDR) pathogens were the main prognostic factor for poor outcomes (aOR: 7.792, p < 0.001).
Conclusions: Our study underscores the need for antimicrobial resistance surveillance, early detection and prompt intervention to improve patient outcomes.
导读:尿路感染(uti)与发病率和死亡率增加有关,但关于继发性菌血症重要性的数据仍然很少。方法:这项回顾性、单中心研究在一家三级大学医院进行,纳入了因尿路感染住院的患者,目的是评估继发性菌血症对临床结果(手术需求、抗生素更换或死亡)的影响,并确定其存在的预测因素。结果:共纳入232例患者,56例(24.1%)发生继发性菌血症。菌血症组CRP水平较高(18 mg/dL vs. 8 mg/dL, p < 0.01),血红蛋白水平较低(11.1 vs. 12 g/dL, p < 0.01),疾病严重程度评分较高。医院获得性感染是菌血症的独立预测因子(aOR: 4.440, p = 0.045)。菌血症患者住院时间较长(8.5天vs. 4天,p < 0.01),而其存在与死亡率独立相关(OR 11.01, 95% CI 1.19-101.50, p = 0.034)。耐多药(MDR)病原体是预后不良的主要预后因素(aOR: 7.792, p < 0.001)。结论:我们的研究强调了进行抗生素耐药性监测、早期发现和及时干预以改善患者预后的必要性。
{"title":"Bacteremic versus Non-Bacteremic Urinary Tract Infections: Predictors of Poor Clinical Outcome.","authors":"Eleni Polyzou, Stamatia Tsoupra, Maria Gavatha, Katerina Skintzi, Anne-Lise Delastic, Achilleas Livieratos, Vasiliki Niarou, Charalambos Gogos, Karolina Akinosoglou","doi":"10.2478/rjim-2025-0025","DOIUrl":"10.2478/rjim-2025-0025","url":null,"abstract":"<p><strong>Introduction: </strong>Urinary tract infections (UTIs) are associated with increased morbidity and mortality, yet data on the importance of secondary bacteremia remain scarce.</p><p><strong>Methods: </strong>This retrospective, single-center study was conducted at a tertiary university hospital and included patients, hospitalized for UTIs, in order to assess the impact of secondary bacteremia on clinical outcomes (need for surgery, antibiotic change or death) and identify predictors for its presence.</p><p><strong>Results: </strong>A total of 232 patients were included, with 56 (24.1%) developing secondary bacteremia. The bacteremia group exhibited higher CRP levels (18 mg/dL vs. 8 mg/dL, p < 0.01), lower hemoglobin (11.1 vs. 12 g/dL, p < 0.01), and higher disease severity scores. Hospital-acquired infections were an independent predictor of bacteremia (aOR: 4.440, p = 0.045). Patients with bacteremia exhibited longer hospital stays (8.5 vs. 4 days, p < 0.01) while its presence was independently associated with mortality (OR 11.01, 95% CI 1.19-101.50, p = 0.034)Multidrug-resistant (MDR) pathogens were the main prognostic factor for poor outcomes (aOR: 7.792, p < 0.001).</p><p><strong>Conclusions: </strong>Our study underscores the need for antimicrobial resistance surveillance, early detection and prompt intervention to improve patient outcomes.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashaq Hussain Parrey, Basharat Kassana, Hilal Bhat, Mohd Ismail
Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by sustained eosinophilia and multi-organ involvement resulting from eosinophil-mediated tissue injury. The condition may arise from diverse etiologies, including clonal myeloproliferative disorders, autoimmune diseases, infections, and idiopathic causes, posing significant diagnostic challenges.
Objective: To describe and analyze the varied clinical manifestations, etiologies, and outcomes of patients presenting with hypereosinophilia in a tertiary-care setting.
Methods: This case series includes five patients with persistent eosinophilia (absolute eosinophil count >1500 cells/μL) who presented with distinct systemic manifestations. All patients underwent detailed clinical, laboratory, and imaging evaluations to determine the underlying cause and extent of organ involvement.
Results: The clinical presentations were highly variable, including cerebral infarcts due to HES-related vasculopathy, disseminated fungal infection with lymph node and bone marrow eosinophilia, ANCA-associated vasculitis with neuropathy, bronchial asthma with marked eosinophilia, and eosinophilic gastrointestinal and hepatic disease. Corticosteroid therapy was the mainstay of treatment, supplemented with antifungal and immunosuppressive agents when indicated. Most patients showed significant improvement, though one had residual neurological deficits.
Conclusion: Hypereosinophilia can manifest through diverse pathophysiological mechanisms affecting nearly any organ system. Early recognition, exclusion of secondary causes, and timely initiation of corticosteroids or targeted therapies are essential to prevent irreversible organ damage and improve clinical outcomes.
{"title":"Hypereosinophilia: Clinical Presentations and Diagnostic Distinction Between Syndromic and Reactive Entities - A Case Series.","authors":"Ashaq Hussain Parrey, Basharat Kassana, Hilal Bhat, Mohd Ismail","doi":"10.2478/rjim-2025-0024","DOIUrl":"https://doi.org/10.2478/rjim-2025-0024","url":null,"abstract":"<p><strong>Background: </strong>Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by sustained eosinophilia and multi-organ involvement resulting from eosinophil-mediated tissue injury. The condition may arise from diverse etiologies, including clonal myeloproliferative disorders, autoimmune diseases, infections, and idiopathic causes, posing significant diagnostic challenges.</p><p><strong>Objective: </strong>To describe and analyze the varied clinical manifestations, etiologies, and outcomes of patients presenting with hypereosinophilia in a tertiary-care setting.</p><p><strong>Methods: </strong>This case series includes five patients with persistent eosinophilia (absolute eosinophil count >1500 cells/μL) who presented with distinct systemic manifestations. All patients underwent detailed clinical, laboratory, and imaging evaluations to determine the underlying cause and extent of organ involvement.</p><p><strong>Results: </strong>The clinical presentations were highly variable, including cerebral infarcts due to HES-related vasculopathy, disseminated fungal infection with lymph node and bone marrow eosinophilia, ANCA-associated vasculitis with neuropathy, bronchial asthma with marked eosinophilia, and eosinophilic gastrointestinal and hepatic disease. Corticosteroid therapy was the mainstay of treatment, supplemented with antifungal and immunosuppressive agents when indicated. Most patients showed significant improvement, though one had residual neurological deficits.</p><p><strong>Conclusion: </strong>Hypereosinophilia can manifest through diverse pathophysiological mechanisms affecting nearly any organ system. Early recognition, exclusion of secondary causes, and timely initiation of corticosteroids or targeted therapies are essential to prevent irreversible organ damage and improve clinical outcomes.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Numerous studies have demonstrated a connection between heightened arterial stiffness (AS) and cardiovascular disease. Over time, several techniques have been devised to gauge arterial stiffness.
Objective: This study aims to investigate the correlation between AS, measured using the PWV method on the arm, and the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score derived from coronary angiography (CAG).
Materials and methods: The cohort comprised 53 patients (51.0%) diagnosed with non-ST elevation myocardial infarction (NSTEMI) and 51 patients (49.0%) diagnosed with ST elevation myocardial infarction (STEMI), all aged between 18 and 80 years. Using the 'Mobil-O-Graph® ARCsolver algorithm' device, we measured parameters such as PWV, augmentation index (AIx), and arterial blood pressure for all participants. The SYNTAX score was employed to gauge the severity and extent of coronary artery disease.
Results: The patients' average age stood at 61.36 years, with 61 (60.6%) being male and 43 (39.4%) female. The mean BMI was recorded at 28.43 kg/m2. Upon comparing the patient groups based on PWV measurements, intriguing insights emerged. Specifically, within the NSTEMI group, a noteworthy positive correlation emerged between PWV and key factors such as age, RDW (Red Cell Distribution Width), blood urea nitrogen (BUN) levels, and SYNTAX score (p<0.05).
Conclusion: The elevation of PWV levels proved to be notably valuable in anticipating the severity of coronary artery disease in NSTEMI patients. Conversely, in STEMI patients, heightened PWV emerged as a predictor of an unfavorable prognosis, aligned with higher clinical risk scores.
背景:大量研究表明动脉硬化(AS)升高与心血管疾病之间存在联系。随着时间的推移,人们发明了几种测量动脉硬度的技术。目的:本研究旨在探讨采用PWV方法在手臂上测量的AS与冠状动脉造影(CAG)得出的SYNTAX (PCI with Taxus and Cardiac Surgery的协同作用)评分之间的相关性。材料与方法:该队列包括53例(51.0%)诊断为非ST段抬高型心肌梗死(NSTEMI)和51例(49.0%)诊断为ST段抬高型心肌梗死(STEMI),年龄均在18 ~ 80岁之间。使用“mobile - o - graph®ARCsolver算法”设备,我们测量了所有参与者的PWV、增强指数(AIx)和动脉血压等参数。SYNTAX评分用于衡量冠状动脉疾病的严重程度和范围。结果:患者平均年龄61.36岁,其中男性61例(60.6%),女性43例(39.4%)。平均BMI为28.43 kg/m2。在比较基于PWV测量的患者组后,出现了有趣的见解。具体而言,在NSTEMI组中,PWV与年龄、RDW(红细胞分布宽度)、血尿素氮(BUN)水平和SYNTAX评分等关键因素之间存在显著的正相关。结论:PWV水平升高在预测NSTEMI患者冠状动脉疾病严重程度方面具有显著价值。相反,在STEMI患者中,PWV升高是不良预后的预测因子,与较高的临床风险评分一致。
{"title":"The importance of arterial stiffness parameters for predicting Syntax Score in acute coronary syndrome.","authors":"Semih Gülle, Cenk Ekmekci, Harun Akar, Öner Özdoğan","doi":"10.2478/rjim-2025-0023","DOIUrl":"https://doi.org/10.2478/rjim-2025-0023","url":null,"abstract":"<p><strong>Background: </strong>Numerous studies have demonstrated a connection between heightened arterial stiffness (AS) and cardiovascular disease. Over time, several techniques have been devised to gauge arterial stiffness.</p><p><strong>Objective: </strong>This study aims to investigate the correlation between AS, measured using the PWV method on the arm, and the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score derived from coronary angiography (CAG).</p><p><strong>Materials and methods: </strong>The cohort comprised 53 patients (51.0%) diagnosed with non-ST elevation myocardial infarction (NSTEMI) and 51 patients (49.0%) diagnosed with ST elevation myocardial infarction (STEMI), all aged between 18 and 80 years. Using the 'Mobil-O-Graph® ARCsolver algorithm' device, we measured parameters such as PWV, augmentation index (AIx), and arterial blood pressure for all participants. The SYNTAX score was employed to gauge the severity and extent of coronary artery disease.</p><p><strong>Results: </strong>The patients' average age stood at 61.36 years, with 61 (60.6%) being male and 43 (39.4%) female. The mean BMI was recorded at 28.43 kg/m<sup>2</sup>. Upon comparing the patient groups based on PWV measurements, intriguing insights emerged. Specifically, within the NSTEMI group, a noteworthy positive correlation emerged between PWV and key factors such as age, RDW (Red Cell Distribution Width), blood urea nitrogen (BUN) levels, and SYNTAX score (p<0.05).</p><p><strong>Conclusion: </strong>The elevation of PWV levels proved to be notably valuable in anticipating the severity of coronary artery disease in NSTEMI patients. Conversely, in STEMI patients, heightened PWV emerged as a predictor of an unfavorable prognosis, aligned with higher clinical risk scores.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheng-Hao Li, Lu Zhang, Hong-Juan Li, Ye Li, Yan-Min Zheng, Qing-Qing Wang
Objective: To elucidate the impact of left ventricular diastolic dysfunction (LVDD) on the risk of medium-term poor prognosis in patients with cirrhotic ascites.
Methods: A total of 194 patients with cirrhotic ascites were included in this retrospective study and categorized into two groups (LVDD and non-LVDD) based on echocardiography findings. Lasso and univariate Cox regression analyses were initially used to screen potential influencing factors of 1-year mortality from basic clinical data. Multivariate Cox regression was then performed to identify independent risk factors. Kaplan-Meier (K-M) and time-dependent receiver operating characteristic (ROC) curves were used to assess the predictive value of LVDD for 1-year mortality. Subgroup analysis was also conducted based on the presence or absence of hepatic malignancy.
Results: (1) LVDD was present in 47.4% (92/194) of patients with cirrhotic ascites; (2) Regression analyses (Lasso, univariate Cox, and multivariate Cox) revealed that LVDD (hazard ratio = 2.109, 95% confidence interval [1.279-3.478], P = 0.003) was an independent risk factor for 1-year mortality; (3) Time-dependent ROC curves demonstrated that the predictive performance of LVDD for 360-day mortality, in the overall population and patients without hepatic malignancy, was comparable to that of traditional Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores (P > 0.05 for all).
Conclusion: LVDD increases the risk of 1-year mortality in patients with cirrhotic ascites, particularly in those without hepatic malignancy.
{"title":"Left Ventricular Diastolic Dysfunction Increases the Risk of Medium-term Mortality in Patients with Cirrhotic Ascites.","authors":"Sheng-Hao Li, Lu Zhang, Hong-Juan Li, Ye Li, Yan-Min Zheng, Qing-Qing Wang","doi":"10.2478/rjim-2025-0022","DOIUrl":"https://doi.org/10.2478/rjim-2025-0022","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the impact of left ventricular diastolic dysfunction (LVDD) on the risk of medium-term poor prognosis in patients with cirrhotic ascites.</p><p><strong>Methods: </strong>A total of 194 patients with cirrhotic ascites were included in this retrospective study and categorized into two groups (LVDD and non-LVDD) based on echocardiography findings. Lasso and univariate Cox regression analyses were initially used to screen potential influencing factors of 1-year mortality from basic clinical data. Multivariate Cox regression was then performed to identify independent risk factors. Kaplan-Meier (K-M) and time-dependent receiver operating characteristic (ROC) curves were used to assess the predictive value of LVDD for 1-year mortality. Subgroup analysis was also conducted based on the presence or absence of hepatic malignancy.</p><p><strong>Results: </strong>(1) LVDD was present in 47.4% (92/194) of patients with cirrhotic ascites; (2) Regression analyses (Lasso, univariate Cox, and multivariate Cox) revealed that LVDD (hazard ratio = 2.109, 95% confidence interval [1.279-3.478], <i>P</i> = 0.003) was an independent risk factor for 1-year mortality; (3) Time-dependent ROC curves demonstrated that the predictive performance of LVDD for 360-day mortality, in the overall population and patients without hepatic malignancy, was comparable to that of traditional Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores (<i>P</i> > 0.05 for all).</p><p><strong>Conclusion: </strong>LVDD increases the risk of 1-year mortality in patients with cirrhotic ascites, particularly in those without hepatic malignancy.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18eCollection Date: 2025-12-01DOI: 10.2478/rjim-2025-0019
Valentin Nica, Medeea Badii, Orsolya Gaal, Georgiana Cabău, Maartje Cleophas, Akshayata Naidu, Ioana Hotea, Tim L Jansen, Cristina Pamfil, Simona Rednic, Radu A Popp, Yang Li, Tania O Crișan, Leo A B Joosten
Introduction: Monosodium urate (MSU) crystals are the primary cause of gout, however the knowledge on MSU crystals exposure and inflammatory changes found in immune cells is diverse, with reports ranging from very limited inflammatory effects to substantial reprogramming of the cells induced by MSU crystals alone. We examine the IL-1β production patterns and the transcriptomic signature in response to MSU crystals alone or in combination with TLR ligands in freshly isolated primary human peripheral blood mononuclear cells (PBMCs).
Materials and methods: PBMCs were isolated by density gradient centrifugation and were stimulated for 24 hours with palmitate in the presence or absence of MSU crystals, followed by cytokine production measurement by ELISA. Two bulk RNA-sequencing analyses were performed independently following the same experimental conditions using PBMCs of patients with gout stimulated with medium control, palmitate and LPS in the presence or absence of MSU crystals.
Results: MSU crystals alone induced a small but significant increase in IL-1β production in human PBMCs. IL-1β production was significantly increased when PBMCs were stimulated with palmitate and this was further amplified by the palmitate-MSU combination. Of high interest, MSU crystals alone or in combination with other stimuli caused no significant transcriptomic alterations.
Conclusions: We confirm the synergistic effect of MSU crystals with palmitate that leads to higher IL-1β production. Transcriptomic analysis shows that MSU crystal exposure is not associated with major transcriptional changes in PBMCs. This suggests that the production of IL-1β in response to MSU crystals may largely be regulated at the post-transcriptional level and additional synergistic stimuli are likely required to fully explain the inflammatory response observed clinically in gout. Moreover, this could also bear relevance for other metabolic disorders associated to hyperuricemia where asymptomatic MSU crystal deposition may be present.
{"title":"Monosodium urate crystals exposure is associated with limited transcriptional changes in primary human PBMCs.","authors":"Valentin Nica, Medeea Badii, Orsolya Gaal, Georgiana Cabău, Maartje Cleophas, Akshayata Naidu, Ioana Hotea, Tim L Jansen, Cristina Pamfil, Simona Rednic, Radu A Popp, Yang Li, Tania O Crișan, Leo A B Joosten","doi":"10.2478/rjim-2025-0019","DOIUrl":"10.2478/rjim-2025-0019","url":null,"abstract":"<p><strong>Introduction: </strong>Monosodium urate (MSU) crystals are the primary cause of gout, however the knowledge on MSU crystals exposure and inflammatory changes found in immune cells is diverse, with reports ranging from very limited inflammatory effects to substantial reprogramming of the cells induced by MSU crystals alone. We examine the IL-1β production patterns and the transcriptomic signature in response to MSU crystals alone or in combination with TLR ligands in freshly isolated primary human peripheral blood mononuclear cells (PBMCs).</p><p><strong>Materials and methods: </strong>PBMCs were isolated by density gradient centrifugation and were stimulated for 24 hours with palmitate in the presence or absence of MSU crystals, followed by cytokine production measurement by ELISA. Two bulk RNA-sequencing analyses were performed independently following the same experimental conditions using PBMCs of patients with gout stimulated with medium control, palmitate and LPS in the presence or absence of MSU crystals.</p><p><strong>Results: </strong>MSU crystals alone induced a small but significant increase in IL-1β production in human PBMCs. IL-1β production was significantly increased when PBMCs were stimulated with palmitate and this was further amplified by the palmitate-MSU combination. Of high interest, MSU crystals alone or in combination with other stimuli caused no significant transcriptomic alterations.</p><p><strong>Conclusions: </strong>We confirm the synergistic effect of MSU crystals with palmitate that leads to higher IL-1β production. Transcriptomic analysis shows that MSU crystal exposure is not associated with major transcriptional changes in PBMCs. This suggests that the production of IL-1β in response to MSU crystals may largely be regulated at the post-transcriptional level and additional synergistic stimuli are likely required to fully explain the inflammatory response observed clinically in gout. Moreover, this could also bear relevance for other metabolic disorders associated to hyperuricemia where asymptomatic MSU crystal deposition may be present.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":"300-309"},"PeriodicalIF":0.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17eCollection Date: 2025-12-01DOI: 10.2478/rjim-2025-0018
Andreea Cristina Ivănescu, Georgeta Camelia Badea, Gheorghe-Andrei Dan
We present the longitudinal evolution of a previously published case of hypereosinophilic syndrome (HES) with cardiac involvement. A 27-year-old woman initially presented with eosinophilic myocarditis and peripheral neuropathy in the absence of a clear etiology, fulfilling criteria for idiopathic HES. Despite thorough investigations, eosinophilic granulomatosis with polyangiitis (EGPA) could not be confirmed due to the lack of clear criteria. The patient responded favorably to corticosteroids and heart failure treatment, with normalization of eosinophil count and improvement of left ventricular systolic function to near-normal parameters. However, during the following 1.5 years, she developed persistent asthma and subsequently presented with recurrent eosinophilia, severe fatigue, and systemic symptoms. This constellation now fulfilled the American College of Rheumatology and Lanham criteria for EGPA. Pulse therapy with intravenous methylprednisolone was initiated, followed by initiation of Rituximab (500 mg bid), and afterward maintained on a remission protocol consisting of Rituximab and gradual tapering. This protocol led to a clinical and biological improvement. Cardiac function remained unaffected. This updated case highlights the evolving nature of EGPA and reinforces the importance of long-term follow-up in patients with hypereosinophilia and cardiac involvement. Atypical presentations of disease underscore the importance of maintaining a high index of clinical suspicion, accompanied by diligent follow-ups, to ensure accurate and timely diagnosis. Early diagnosis and prompt initiation of therapy remain crucial for improving prognosis and preventing organ damage.
{"title":"The hypereosinophilia dilemma: what's beyond cardiac involvement?","authors":"Andreea Cristina Ivănescu, Georgeta Camelia Badea, Gheorghe-Andrei Dan","doi":"10.2478/rjim-2025-0018","DOIUrl":"10.2478/rjim-2025-0018","url":null,"abstract":"<p><p>We present the longitudinal evolution of a previously published case of hypereosinophilic syndrome (HES) with cardiac involvement. A 27-year-old woman initially presented with eosinophilic myocarditis and peripheral neuropathy in the absence of a clear etiology, fulfilling criteria for idiopathic HES. Despite thorough investigations, eosinophilic granulomatosis with polyangiitis (EGPA) could not be confirmed due to the lack of clear criteria. The patient responded favorably to corticosteroids and heart failure treatment, with normalization of eosinophil count and improvement of left ventricular systolic function to near-normal parameters. However, during the following 1.5 years, she developed persistent asthma and subsequently presented with recurrent eosinophilia, severe fatigue, and systemic symptoms. This constellation now fulfilled the American College of Rheumatology and Lanham criteria for EGPA. Pulse therapy with intravenous methylprednisolone was initiated, followed by initiation of Rituximab (500 mg bid), and afterward maintained on a remission protocol consisting of Rituximab and gradual tapering. This protocol led to a clinical and biological improvement. Cardiac function remained unaffected. This updated case highlights the evolving nature of EGPA and reinforces the importance of long-term follow-up in patients with hypereosinophilia and cardiac involvement. Atypical presentations of disease underscore the importance of maintaining a high index of clinical suspicion, accompanied by diligent follow-ups, to ensure accurate and timely diagnosis. Early diagnosis and prompt initiation of therapy remain crucial for improving prognosis and preventing organ damage.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":"316-322"},"PeriodicalIF":0.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-14eCollection Date: 2025-12-01DOI: 10.2478/rjim-2025-0017
Vladimir Bratu, Ruxandra Copciag, Roxana Rimbas, Dragos Vinereanu
Purpose: To assess reproducibility of 2D echocardiography parameters of right ventricular systolic function, such as tricuspid annular plane systolic excursion, right ventricular systolic wave velocity, fractional area change, and 3D right ventricular ejection fraction, through measurements performed by operators with different levels of experience, in patients with acute myocardial infarction.
Methods: Measurements were performed offline, independently, by three echocardiographers with different levels of experience: Reader 1 - advanced (5 years of training in 2DE, 3 years in 3DE); Reader 2 - intermediate (3 years of training in 2DE, 1 year in 3DE); Reader 3 - beginner (1 year of training in 2DE, 3 months in 3DE). Interobserver variability and agreement between readers were compared using Bland-Altman plots, as bias and limits of agreement (LOA), Pearson correlations and intraclass correlation coefficients.
Results: 63 patients (52 males, 56.8±10.3 years) were analysed. All measurements showed excellent interobserver variability and agreement. Bias values were low, and LOA intervals were narrow, across all assessed parameters. Generally, bias values were lower between the advanced and intermediate readers with the exception of FAC: R1 vs R2 - bias 0.36, LOA -4.9;5.62 (r=0.96, p<0.001); R1 vs R3 - bias 0.09, LOA -6.4;6.6 (r=0.94, p<0.001); R2 vs R3 - bias -0.27, LOA -8.1;7.5 (r=0.91, p<0.001). Pearson correlation coefficients were excellent (>0.88) with significant p-values across all parameters (p<0.001). ICC were also excellent (>0.967).
Conclusion: 2DE and 3DE parameters of right ventricular (RV) systolic function are highly reproducible, independent of operator experience, in patients presenting with acute myocardial infarction.
{"title":"Reproducibility of parameters assessing right ventricular systolic function in patients after an acute myocardial infarction.","authors":"Vladimir Bratu, Ruxandra Copciag, Roxana Rimbas, Dragos Vinereanu","doi":"10.2478/rjim-2025-0017","DOIUrl":"10.2478/rjim-2025-0017","url":null,"abstract":"<p><strong>Purpose: </strong>To assess reproducibility of 2D echocardiography parameters of right ventricular systolic function, such as tricuspid annular plane systolic excursion, right ventricular systolic wave velocity, fractional area change, and 3D right ventricular ejection fraction, through measurements performed by operators with different levels of experience, in patients with acute myocardial infarction.</p><p><strong>Methods: </strong>Measurements were performed offline, independently, by three echocardiographers with different levels of experience: Reader 1 - advanced (5 years of training in 2DE, 3 years in 3DE); Reader 2 - intermediate (3 years of training in 2DE, 1 year in 3DE); Reader 3 - beginner (1 year of training in 2DE, 3 months in 3DE). Interobserver variability and agreement between readers were compared using Bland-Altman plots, as bias and limits of agreement (LOA), Pearson correlations and intraclass correlation coefficients.</p><p><strong>Results: </strong>63 patients (52 males, 56.8±10.3 years) were analysed. All measurements showed excellent interobserver variability and agreement. Bias values were low, and LOA intervals were narrow, across all assessed parameters. Generally, bias values were lower between the advanced and intermediate readers with the exception of FAC: R1 vs R2 - bias 0.36, LOA -4.9;5.62 (r=0.96, p<0.001); R1 vs R3 - bias 0.09, LOA -6.4;6.6 (r=0.94, p<0.001); R2 vs R3 - bias -0.27, LOA -8.1;7.5 (r=0.91, p<0.001). Pearson correlation coefficients were excellent (>0.88) with significant p-values across all parameters (p<0.001). ICC were also excellent (>0.967).</p><p><strong>Conclusion: </strong>2DE and 3DE parameters of right ventricular (RV) systolic function are highly reproducible, independent of operator experience, in patients presenting with acute myocardial infarction.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":"277-286"},"PeriodicalIF":0.8,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Acute type A aortic dissection (ATAAD) remains one of the most time-critical cardiovascular emergencies, with early mortality continuing to pose substantial clinical and organizational challenges. Large-scale observational registries offer valuable insights into real-world outcomes across healthcare systems.
Aim: To synthesize and compare early mortality rates in patients with ATAAD as reported by national and multicentre registries.
Methods: A structured search was conducted in PubMed, Google Scholar and the Cochrane Library for studies published within the last 10 years. We included registry-based studies reporting in-hospital, 30-day, operative or 48-hour mortality following ATAAD. Study characteristics, demographic profiles and preoperative risk factors were extracted.
Results: A total of 20 studies, comprising 77,267 patients, were included. In-hospital mortality was reported in 13 registries (n = 50,470), with rates ranging from 5% to 29%. Thirty-day mortality was reported in 5 registries (n = 19,521) and operative mortality in 2 registries (n = 14,825). Substantial variation in outcome definitions and case inclusion criteria limited direct comparability.
Conclusions: Early mortality in ATAAD remains high and heterogeneous across registries. Strengthening global registry participation and adopting standardized reporting practices are essential steps toward improving risk stratification, guiding clinical decisions, and advancing equitable care in ATAAD.
{"title":"Mortality in acute type A aortic dissection - A systematic review based on contemporary registries.","authors":"Diana-Cristina Matei, Cornel Robu, Celia Georgiana Ciobanu, Oliviana Dana Geavlete, Elena-Laura Antohi, RăZvan Ilie Radu, Șerban Bubenek, Vlad Anton Iliescu, Ovidiu Chioncel","doi":"10.2478/rjim-2025-0015","DOIUrl":"10.2478/rjim-2025-0015","url":null,"abstract":"<p><strong>Background: </strong>Acute type A aortic dissection (ATAAD) remains one of the most time-critical cardiovascular emergencies, with early mortality continuing to pose substantial clinical and organizational challenges. Large-scale observational registries offer valuable insights into real-world outcomes across healthcare systems.</p><p><strong>Aim: </strong>To synthesize and compare early mortality rates in patients with ATAAD as reported by national and multicentre registries.</p><p><strong>Methods: </strong>A structured search was conducted in PubMed, Google Scholar and the Cochrane Library for studies published within the last 10 years. We included registry-based studies reporting in-hospital, 30-day, operative or 48-hour mortality following ATAAD. Study characteristics, demographic profiles and preoperative risk factors were extracted.</p><p><strong>Results: </strong>A total of 20 studies, comprising 77,267 patients, were included. In-hospital mortality was reported in 13 registries (n = 50,470), with rates ranging from 5% to 29%. Thirty-day mortality was reported in 5 registries (n = 19,521) and operative mortality in 2 registries (n = 14,825). Substantial variation in outcome definitions and case inclusion criteria limited direct comparability.</p><p><strong>Conclusions: </strong>Early mortality in ATAAD remains high and heterogeneous across registries. Strengthening global registry participation and adopting standardized reporting practices are essential steps toward improving risk stratification, guiding clinical decisions, and advancing equitable care in ATAAD.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":" ","pages":"209-220"},"PeriodicalIF":0.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144744607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-26eCollection Date: 2025-09-01DOI: 10.2478/rjim-2025-0014
Paula Alexandra Vulciu, Luminita Pilat, Norberth-Istvan Varga, Voicu Dascau, Calin Popa, Maria-Daniela Mot, Paula Irina Barata, Imola Donath Miklos, Maria Puschita
Background and objectives: Heart failure (HF) with left ventricle ejection fraction (LVEF) >45% lacks reliable biomarkers for risk stratification complicating its management, as it encompasses both heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) and mildly reduced ejection fraction (HFmrEF, LVEF 45-49.9%). This study aimed to evaluate serum tetranectin (TETRA) as a novel biomarker for assessing disease severity and predicting mortality in patients with HF with EF >45%.
Materials and methods: In a prospective cohort study including 116 patients HF with EF>45% from a single center in Arad, Romania, stratified by NYHA class (G1: NYHA I, n=48; G2: NYHA II, n=37; G3: NYHA III-IV, n=31), serum TETRA levels were measured using ELISA. Echocardiographic parameters (E/e' ratio, LAVI, LAS, GLS, LVEF) and NT-proBNP were assessed at baseline, with all-cause mortality (9 deaths) tracked over a 12-month follow-up.
Results: Median TETRA levels decreased with worsening NYHA class (G1: 48.9 ng/mL, G2: 33.2 ng/mL, G3: 27.6 ng/mL; p < 0.001) and correlated negatively with NT-proBNP (rho = -0.66, p < 0.001), E/e' ratio (rho = -0.58, p = 0.003), and LAVI (rho = -0.52, p = 0.010), while positively correlating with LAS (rho = 0.55, p = 0.005). In univariable Cox analysis, lower TETRA levels were associated with higher all-cause mortality (HR = 1.38 per 10 ng/mL decrease, 95% CI: 1.06-1.81, p = 0.045), but this association was not significant after adjustment for age and NT-proBNP (HR = 1.22, 95% CI: 0.94-1.86, p = 0.112).
Conclusions: TETRA levels are inversely associated with severity in heart failure with EF>45% and may reflect disease progression.
背景和目的:左心室射血分数(LVEF)低于45%的心力衰竭(HF)缺乏可靠的风险分层生物标志物,使其管理复杂化,因为它包括射血分数保留的心力衰竭(HFpEF, LVEF≥50%)和轻度降低的射血分数(HFmrEF, LVEF 45-49.9%)。本研究旨在评估血清四联素(TETRA)作为评估疾病严重程度和预测心力衰竭患者死亡率的一种新的生物标志物。材料和方法:在一项前瞻性队列研究中,来自罗马尼亚Arad单一中心的116例HF伴EF bb0 45%的患者,按NYHA分级(G1: NYHA I, n=48; G2: NYHA II, n=37; G3: NYHA III-IV, n=31),采用ELISA检测血清TETRA水平。在基线时评估超声心动图参数(E/ E比值、LAVI、LAS、GLS、LVEF)和NT-proBNP,并在12个月的随访中跟踪全因死亡率(9例死亡)。结果:TETRA中位水平随NYHA分级加重而降低(G1: 48.9 ng/mL, G2: 33.2 ng/mL, G3: 27.6 ng/mL, p < 0.001),与NT-proBNP (rho = -0.66, p < 0.001)、E/ E′比(rho = -0.58, p = 0.003)、LAVI (rho = -0.52, p = 0.010)呈负相关,与LAS呈正相关(rho = 0.55, p = 0.005)。在单变量Cox分析中,较低的TETRA水平与较高的全因死亡率相关(每降低10 ng/mL, HR = 1.38, 95% CI: 1.06-1.81, p = 0.045),但在调整年龄和NT-proBNP后,这种关联不显著(HR = 1.22, 95% CI: 0.94-1.86, p = 0.112)。结论:TETRA水平与心力衰竭的严重程度呈负相关,EF bb0为45%,可能反映疾病进展。
{"title":"Tetranectin as a potential biomarker in heart failure with ejection fraction >45%: A prospective cohort study.","authors":"Paula Alexandra Vulciu, Luminita Pilat, Norberth-Istvan Varga, Voicu Dascau, Calin Popa, Maria-Daniela Mot, Paula Irina Barata, Imola Donath Miklos, Maria Puschita","doi":"10.2478/rjim-2025-0014","DOIUrl":"https://doi.org/10.2478/rjim-2025-0014","url":null,"abstract":"<p><strong>Background and objectives: </strong>Heart failure (HF) with left ventricle ejection fraction (LVEF) >45% lacks reliable biomarkers for risk stratification complicating its management, as it encompasses both heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) and mildly reduced ejection fraction (HFmrEF, LVEF 45-49.9%). This study aimed to evaluate serum tetranectin (TETRA) as a novel biomarker for assessing disease severity and predicting mortality in patients with HF with EF >45%.</p><p><strong>Materials and methods: </strong>In a prospective cohort study including 116 patients HF with EF>45% from a single center in Arad, Romania, stratified by NYHA class (G1: NYHA I, n=48; G2: NYHA II, n=37; G3: NYHA III-IV, n=31), serum TETRA levels were measured using ELISA. Echocardiographic parameters (E/e' ratio, LAVI, LAS, GLS, LVEF) and NT-proBNP were assessed at baseline, with all-cause mortality (9 deaths) tracked over a 12-month follow-up.</p><p><strong>Results: </strong>Median TETRA levels decreased with worsening NYHA class (G1: 48.9 ng/mL, G2: 33.2 ng/mL, G3: 27.6 ng/mL; p < 0.001) and correlated negatively with NT-proBNP (rho = -0.66, p < 0.001), E/e' ratio (rho = -0.58, p = 0.003), and LAVI (rho = -0.52, p = 0.010), while positively correlating with LAS (rho = 0.55, p = 0.005). In univariable Cox analysis, lower TETRA levels were associated with higher all-cause mortality (HR = 1.38 per 10 ng/mL decrease, 95% CI: 1.06-1.81, p = 0.045), but this association was not significant after adjustment for age and NT-proBNP (HR = 1.22, 95% CI: 0.94-1.86, p = 0.112).</p><p><strong>Conclusions: </strong>TETRA levels are inversely associated with severity in heart failure with EF>45% and may reflect disease progression.</p>","PeriodicalId":21463,"journal":{"name":"Romanian Journal of Internal Medicine","volume":"63 3","pages":"251-262"},"PeriodicalIF":0.8,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}