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Objectives: The study aimed to determine the levels of change of the markers related to radiographic progression, such as Dickkopf-1 (DKK-1), sclerostin (SOST), bone morphogenetic protein (BMP)-2 and -4, and interleukin (IL)-17 and -23, in ankylosing spondyloarthritis (AS) during anti-tumor necrosis factor alpha (TNF-α) treatment., Patients and Methods: Fifty-three anti-TNF-α naïve AS patients (34 males, 19 females; median: 38 years; range, 20 to 52 years) refractory to conventional treatments meeting the modified New York criteria or Assessment of SpondyloArthritis International Society classification criteria were enrolled to this cross-sectional, controlled study between October 2015 and January 2017. Fifty healthy volunteers (35 males, 15 females; median: 36 years; range, 18 to 55 years) with similar age and sex characteristics were recruited. Serum DKK-1, BMP-2, BMP-4, SOST, IL-17, and IL-23 levels were measured in both groups. The serum levels of the markers were measured again after about two years (mean follow-up duration of 21.7±6.4 months) in AS patients who started anti-TNF-α treatment. Demographic, clinical characteristics, and laboratory parameters were recorded. The disease activity at the time of inclusion was assessed through the Bath Ankylosing Spondylitis Disease Activity Index., Results: Serum DKK-1, SOST, IL-17, and IL-23 levels in the AS group before anti-TNF-a treatment were significantly higher compared to the control group (p<0.01 for DKK-1, p<0.001 for others). There was no difference regarding serum BMP-4 levels, whereas BMP-2 levels were significantly higher in the control group (p<0.01). Forty (75.47%) AS patients had serum marker levels measured after anti-TNF-α treatment. No significant change was observed in the serum levels of these 40 patients measured 21.7±6.4 months after the initiation of anti-TNF-α treatment (p>0.05 for all)., Conclusion: In AS patients, there was no change in DKK-1/SOST, BMP, and IL-17/23 cascade with anti-TNF-α treatment. This finding may suggest that these pathways act independently of each other, and their local effects are not influenced by systemic inflammation., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

Objectives: This study aims to investigate the levels of bone morphogenic proteins (BMPs), one of the pathways affecting bone turnover in these diseases, and to investigate their relationship with disease activity., Patients and Methods: Between September 2013 and July 2015, a total of 100 ankylosing spondylitis (AS) patients (53 males, 48 females; median age: 40 years; range, 18 to 62 years), 58 rheumatoid arthritis (RA) patients (25 males, 33 females; median age: 40.5 years; range, 26 to 59 years), and 102 age- and sex-matched healthy controls (55 males, 47 females; median age: 38 years; range, 18 to 55 years) were included in the study. In all groups, serum BMP-2 and BMP-4 levels were measured using enzyme-linked immunosorbent assay (ELISA). Demographic data (age, sex, duration of disease) and acute phase reactants of the patients at the final visit were recorded. Disease activity was assessed through the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP) for AS patients and through the Disease Activity Score-28-CRP (DAS-28-CRP) for RA patients., Results: The median BMP-2 values were found to be significantly higher in the RA group compared to the other groups and in the control group compared to the AS group (p<0.001 for both). There was no significant difference between the groups in terms of median BMP-4 values (p>0.05). No significant relationship was found between serum BMP-2 and BMP-4 levels and disease activity in both AS and RA patients, while there was a weak positive correlation between erythrocyte sedimentation rate and CRP levels with BMP-2 level in RA patients (p=0.014, r=0.320 and p=0.029, r=0.287, respectively)., Conclusion: Our study results suggest that the BMP pathway may have different dual effects in AS and RA patients depending on the underlying pathogenesis, and that local effects are more prominent than serum levels., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish League Against Rheumatism.)

Background: In clinical practice, it is hard to judge the level of disease activity in some patients with ankylosing spondylitis (AS) who have low traditional acute phase reactant values such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) but have considerable pain and inflammation. The aim of this study is to investigate plasma pentraxin 3 (PTX3) and serum amyloid P (SAP) levels in patients with AS who had normal ESR and CRP but high disease activity., Methods: 100 AS patients and 100 gender- and age-matched controls were included. Epidemiological, clinical, and treatment data and plasma levels of CRP, ESR, PTX3, and SAP were evaluated. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP were used for evaluating disease activity. Plasma levels of PTX3 and SAP were compared between AS patients and controls and also among AS patients with active and inactive disease., Results: AS patients had significantly higher plasma levels of PTX3 and SAP than controls. There were not any significant correlations between PTX3 and SAP with BASDAI, ASDAS-CRP, and ESR. There was a positive correlation between PTX3 and CRP. No significant difference in plasma levels of PTX3 and SAP was observed between patients with active disease and inactive disease, both with normal ESR and CRP levels. Disease duration and treatment did not influence plasma PTX3 levels., Conclusions: In patients with AS, plasma levels of PTX3 and SAP were found to be elevated when compared to healthy controls. No association was observed between these biomarkers and disease activity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ali Erhan Özdemirel et al.)

Background: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy., Patients and Methods: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed., Results: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy., Conclusions: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.

Objective: Inflammatory breast cancer (IBC) has an unfavourable prognosis despite the advances made in the treatment of breast cancer. Our study aimed to define immunohistochemistry-based surrogate subtype distribution to determine whether the breast cancer subtype accompanied survival outcome differences in IBC., Materials and Methods: Medical records of female breast cancer patients with non-metastatic inflammatory breast cancer admitted to our clinic between March 2000 and December 2015 were retrospectively reviewed. Patient demographics, clinical and pathological feature of the primary tumour, adjuvant treatment options and survival data were analysed. Intrinsic breast cancer subtypes were defined according to ER, PR, HER-2 and ki-67 status., Results: We identified 129 non-metastatic inflammatory breast cancer patients. Median follow-up was 73 months. 10 (7.7%) were luminal A-like, 67 (51.9%) were luminal B-like, 37 (28.6%) were HER-2 positive, and 15 (11.6%) were triple negative (TNBC) by immunohistochemistry. There were no statistically significant differences between subtypes in terms of histological type, grade, tumour size and lymph node status. Median disease-free survival was 47 months (95% confidence interval [CI] 29.2-82.6) and median overall survival was 75 months (95% CI 64.7-90.8). Triple negative breast cancer showed poorer outcome than other subgroups. Presence of TNBC disease was associated with poorer outcome compared to luminal A (HR: 0.19, 95% CI 0.04-0.92, p: 0.039), luminal B (HR: 0.34, 95% CI 0.15-0.74, p: 0.007) and HER-2 positive subgroups (HR: 0.40, 95% CI 0.17-0.94, p:0.037). Luminal A patients had a trend to have a better overall survival which did not reach to a statistical significant difference., Conclusion: Our study put forth that IBC have a poor prognosis irrespective of breast cancer surrogate subtype distribution. Luminal A, the most frequent subtype of breast cancer was the least common in our IBC patient group. TNBC had the worst outcome when compared to other breast cancer subtypes., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Aim: This study aimed to assess the clinical efficacy and toxicity of sunitinib, a targeted-agent, for non-clear cell renal cell carcinoma., Patients and Methods: Sixty-three patients with complete clinical data from 13 oncology Centers were retrospectively evaluated. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse events., Results: The median age of all patients, 38 men (60.3%) and 25 women (39.7%), was 63 years (range=25-82 years). Histological subtypes included 46 (88%) cases of papillary RCC, 10 of chromophobe, and 7 unclassified cases. Median treatment duration was seven months (range=2-86 months). At the time of this analysis, 52 patients had discontinued treatment, 33 of whom had died. Treatment discontinuation was due to disease progression in 43 patients, and toxicity in nine. Dose interruption was necessary in 22 (34.9%) patients, and dose reduction in 27 (42.9%). The objective response rate and disease control rate were 11.1% and 63.5%, respectively. The median PFS and OS were 7.6 months (95% confidence interval (CI)=5.5-9.7 months) and 22.0 months (95% CI=13.4-30.6 months), respectively, with 1-year rates of 64.7% and 33.7%, respectively., Conclusion: Clinical outcome of the metastatic non-clear cell RCC patients with sunitinib treatment seemed to be worse than the historical data of clear cell RCC patients, in terms of PFS, OS and objective response. New and more effective targeted-therapies and better understanding of the underlying molecular processes are necessary to improve survival outcome for these patients., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)