Publications by authors named "Mehmet Akif Ozturk"

127 Publications

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer.

JCO Glob Oncol 2022 Jan;8:e2100153

Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Purpose: Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues.

Methods: A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed.

Results: A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor-positive disease, respectively.

Conclusion: This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.
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http://dx.doi.org/10.1200/GO.21.00153DOI Listing
January 2022

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

Clin Rheumatol 2022 Jan 11. Epub 2022 Jan 11.

Department of Internal Medicine, Division of Rheumatology, Facultyof Medicine, Gazi University, 06100, Ankara, Turkey.

Objective: The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores.

Method: Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively.

Results: Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r =  - 0.675) and ITAS scores (r =  - 0.385), as well as with CRP and CRI.

Conclusion: Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.
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http://dx.doi.org/10.1007/s10067-021-06020-yDOI Listing
January 2022

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma.

Balkan Med J 2021 Dec 20. Epub 2021 Dec 20.

Department of Medical Oncology, Marmara University School of Medicine, İstanbul, Turkey.

Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis.

Aim: To investigate the prognostic value of tissue-resident memory cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas.

Study Design: Retrospective cross-sectional study.

Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account.

Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn's-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn's-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29).

Conclusion: Tissue-resident memory cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.
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http://dx.doi.org/10.5152/balkanmedj.2021.21122DOI Listing
December 2021

Diagnostic utility of serum biomarkers in large vessel vasculitis and their correlation with positron emission tomography.

Mod Rheumatol 2021 Sep 24. Epub 2021 Sep 24.

Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey.

Objectives: To investigate the association between vascular inflammation, as detected by positron emission tomography (PET) imaging and interleukin-6 (IL-6), pentraxin3, and B-cell-activating factor (BAFF) in subjects with LVV.

Methods: The study included newly diagnosed giant cell arteritis (GCA, n = 27) or Takayasu arteritis (n = 9) patients and healthy control (HC, n = 31) subjects. PET scan and blood samples were obtained before the introduction of treatments. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay kits.

Results: Thirty-six patients with LVV (20 females, 16 males; age 64.5 ± 16.6 years) and 31 HC (14 females, 17 males; age 37.1 ± 9.6 years) were included. Serum levels of IL-6, PTX3, and BAFF were increased in patients with newly diagnosed LVV compared with healthy control subjects. In receiver operating characteristics (ROC) analysis, serum IL-6 and BAFF provided excellent discrimination of newly diagnosed LVV patients from HC (area under the ROC curve of >0.90 and >0.80, respectively). None of the inflammatory markers correlated with vascular inflammatory activity determined by PET scanning.

Conclusions: Our results suggest that IL-6 and BAFF may serve as markers of large vessel vasculitis, while PTX3 is not useful. None of the inflammatory markers correlated with PET assessed vasculitis activity.
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http://dx.doi.org/10.1093/mr/roab074DOI Listing
September 2021

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets.

Int J Mol Sci 2021 Sep 14;22(18). Epub 2021 Sep 14.

Department of Medical Oncology, Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK.

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.
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http://dx.doi.org/10.3390/ijms22189926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472415PMC
September 2021

Unraveling the Wide Spectrum of Melanoma Biomarkers.

Diagnostics (Basel) 2021 Jul 26;11(8). Epub 2021 Jul 26.

Department of Medical Oncology, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, UK.

The use of biomarkers in medicine has become essential in clinical practice in order to help with diagnosis, prognostication and prediction of treatment response. Since Alexander Breslow's original report on "melanoma and prognostic values of thickness", providing the first biomarker for melanoma, many promising new biomarkers have followed. These include serum markers, such as lactate dehydrogenase and S100 calcium-binding protein B. However, as our understanding of the DNA mutational profile progresses, new gene targets and proteins have been identified. These include point mutations, such as mutations of the BRAF gene and tumour suppressor gene tP53. At present, only a small number of the available biomarkers are being utilised, but this may soon change as more studies are published. The aim of this article is to provide a comprehensive review of melanoma biomarkers and their utility for current and, potentially, future clinical practice.
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http://dx.doi.org/10.3390/diagnostics11081341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391989PMC
July 2021

Long-term safety and efficacy of anakinra and canakinumab in patients with familial Mediterranean fever: a single-centre real-life study with 101 patients.

Clin Exp Rheumatol 2021 Sep-Oct;39 Suppl 132(5):30-36. Epub 2021 Jun 21.

Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey.

Objectives: Anakinra and canakinumab are the most commonly used agents in colchicine resistant/intolerant patients. In this study we investigated long-term efficacy and safety of anakinra and canakinumab.

Methods: In this retrospective study, we enrolled 101 adult patients with familial Mediterranean fever (FMF). Clinical and laboratory parameters before and after treatment with anakinra/canakinumab and the side effects observed during the treatment were recorded. All patients received anakinra initially and switched to canakinumab, in case of inadequate response/intolerance.

Results: The median (IQR) duration of treatment with anti-IL-1 agents was 35 (24-47.5) months. 101 patients were treated with anakinra and 27 patients with canakinumab. The autoinflammatory diseases activity and attacks decreased with both anakinra and canakinumab. Anakinra was effective in decreasing proteinuria and canakinumab was not effective in decreasing proteinuria in anakinra unresponsive patients. The modified FMF score was achieved in 76.2% of anakinra and 88.9% of canakinumab group. Injection site reactions (ISRs, n:15) was the most common reason of discontinuation of anakinra and most of ISRs developed in first 3 months of treatment. One severe skin rash, two anaphylactic reactions and one severe neutropenia were observed with anakinra; in the first, eighth, twelfth and fiftieth months, respectively. No severe side effects or side effect-related discontinuation of canakinumab were observed.

Conclusions: Anakinra and canakinumab seem to be effective in long-term management of FMF patients. Canakinumab had a favourable safety/tolerability profile. Anakinra is also generally safe, but the serious side effects that may be observed in the short and long-term use should be taken into account.
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October 2021

Evaluation of Asymptomatic Bacteriuria and Urinary Tract Infection in Patients With Primary Sjögren's Syndrome.

Arch Rheumatol 2020 Dec 25;35(4):592-599. Epub 2020 Jun 25.

Department of Internal Medicine, Division of Rheumatology, Gazi University Medical Faculty Hospital, Ankara, Turkey.

Objectives: This study aims to determine the frequency and risk factors of bacteriuria and urinary tract infection (UTI) in patients with primary Sjögren's syndrome (SS) and their differences from healthy individuals and rheumatoid arthritis (RA) patients.

Patients And Methods: The study included 107 female primary SS patients (mean age 50.7±11.6 years; range, 23 to 76 years), 53 healthy female control subjects (mean age 46.8±15.5 years; range 21 to 80 years), and 40 females with RA (mean age 51.7±14.2 years; range, 25 to 79 years). Participants were questioned for UTI risk factors and symptoms. Middle stream urine samples were taken and cultured. All participants were examined with urinary symptom questioning survey of American Urological Association (AUA-7).

Results: The urine cultures were positive in 18 primary SS patients (16.8%), eight RA patients (20%), and two healthy controls (3.7%). Escherichia coli, enterococci, Klebsiella, streptococci, and candida were detected in SS patients' cultures. Extended-spectrum beta-lactamase was positive in three cultures. Asymptomatic bacteriuria was not detected in any SS patient. The highest AUA-7 score was determined in SS group (p=0.031). Nineteen SS patients had vaginal dryness symptom and their AUA-7 scores were higher than the rest of the SS group. The risk of UTI development was not different between those who had or did not have vaginal dryness.

Conclusion: Urinary tract infections are seen more often in SS patients rather than normal population, which may be caused by SS' urinary system effects. It is difficult to distinguish between asymptomatic bacteriuria and infection because of the underlying urinary symptoms. Clinicians must be careful in patients receiving immunosuppressive therapy due to the high frequency of UTIs.
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http://dx.doi.org/10.46497/ArchRheumatol.2020.7427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945699PMC
December 2020

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Turk J Med Sci 2021 08 30;51(4):1695-1701. Epub 2021 Aug 30.

Department of Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkey

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia.

Materials And Methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively.

Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively).

Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.
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http://dx.doi.org/10.3906/sag-2011-273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569734PMC
August 2021

Characteristics of Diabetic Ageing Patients in Nursing Homes: One Center Experience in Turkey.

Nutr Metab Insights 2021 2;14:1178638821990345. Epub 2021 Feb 2.

Department of Internal Medicine, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.

Introduction: Due to its widespread distribution and effects, type 2 diabetes is a frequently researched topic. However, the amount of information about type 2 diabetes in nursing homes residents is inadequate. The aim of this study is to elucidate on the frequency, treatments, comorbidities, and deaths of nursing home residents diagnosed with type 2 diabetes.

Materials And Methods: Type 2 diabetes was evaluated in 612 people accepted to nursing homes as residents between January 2005 and January 2013. Medical records, prescriptions, laboratory results, and comorbidities were evaluated statistically.

Results: Approximately 26% (159) patients of the cohort had either preexisting type 2 diabetes during registration to nursing home or was diagnosed with it during the 8-year follow-up. The prevalence of DM was 25% in males and 26% in females. Average age was 75.7 ± 10.6 in diabetics and 76.7 ± 11.6 in non-diabetics. Hemoglobin, creatinine, triglycerides, HDL-cholesterol, and CRP values were not found to be different between the groups. Hypertension was diagnosed in 75% of diabetics versus 59% of non-diabetics, hyperlipidemia in 21% versus 7% ( < .01); however, atrial fibrillation was more common in non-diabetics ( = .022). There was no difference for survival rate between diabetic and non-diabetic groups ( = .743).

Conclusion: Approximately 1 out of 4 nursing home residents were found to have diabetes, with females being more affected then males. The survival rates both at the diabetic and non-diabetic patients were detected similar. Glucose, total cholesterol, LDL-cholesterol, and blood pressure values which can all impact survival should be closely watched from early on in the disease progress and their values should be optimized.
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http://dx.doi.org/10.1177/1178638821990345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863158PMC
February 2021

Work productivity impairment in patients with familial Mediterranean fever and effects of interleukin-1 antagonists.

Clin Rheumatol 2021 Jul 1;40(7):2865-2871. Epub 2021 Feb 1.

Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, 06100, Ankara, Turkey.

Introduction: Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever, serositis, and arthritis. Some patients suffer from associated inflammatory conditions and damage related to FMF that may potentially impair work productivity which have not been studied to date.

Methods: Consecutive FMF patients who were attending a tertiary referral center and age-and sex-matched healthy subjects enrolled into the study. Disease activity was assessed with autoinflammatory disease activity index (AIDAI) and patient global assessment. Damage was evaluated using Autoinflammatory Disease Damage Index (ADDI). Quality of life (QoL) and work productivity were determined with 36-Item Short Form Health Survey (SF-36) and Work Productivity and Activity Impairment Specific Health Problem v2.0 (WPAI:SHP), respectively.

Results: There were 111 FMF patients, 60 female (54%), mean age 32.7±8.7 years. There were significant impairments in all domains of the SF-36 QoL in FMF patients. Of the 111 patients enrolled, 65 (58.6%) were employed in a paid work. Mean% ±SD impairment in work productivity both assessed as absenteeism (9.3±23.2% vs. 0.7±2.6, p=0.013) and presenteeism (35.2±32.6% vs. 9.6±14.7, p<0.001) were significantly higher in FMF patients compared to healthy subjects. Impairment in work productivity was correlated with the number of attacks, disease activity, colchicine resistance, and disease-associated damage. Impairment was most significant in colchicine-resistant FMF patients but lower in those on interleukin (IL)-1 antagonist treatments.

Conclusions: FMF causes significant work impairment and reduced QoL which is associated with disease activity and damage. The use of IL-1 antagonists may help to improve work productivity and QoL in FMF patients with frequent attacks. Key points • Work productivity is impaired in patients with FMF. • Disease activity was an independent predictor for impaired work productivity. • IL-1 antagonists may improve work productivity and quality of life in FMF patients with frequent attacks.
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http://dx.doi.org/10.1007/s10067-021-05617-7DOI Listing
July 2021

Current and future immunotherapy approaches in ovarian cancer.

Ann Transl Med 2020 Dec;8(24):1714

Division of Medical Oncology, Department of Internal Medicine, Bahcesehir University Faculty of Medicine, Istanbul, Turkey.

Ovarian cancer (OC) is the major cause of gynecologic cancer deaths and relapse is common despite advances in surgery and systemic chemotherapy. Therefore, novel treatments are required to improve long-term outcomes of the disease. Efficacy of immunotherapy was demonstrated in many tumors and it has been since incorporated into clinical practice for them. Although early data form preclinical studies imply that OC has an immunogenic microenvironment, immune checkpoint inhibitors (ICIs) did not produce favorable results in clinical trials to date. This review will highlight data from clinical studies regarding immunotherapy in OC and its combination with other agents as well as immunologic prospects which could strengthen the therapeutic armament against the disease in the future.
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http://dx.doi.org/10.21037/atm-20-4499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812210PMC
December 2020

Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?

Ann Transl Med 2020 Dec;8(24):1706

Medical School, University of Ioannina, Ioannina, Greece.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women, potentially due to ineffectiveness of screening tests for early detection. Patients typically present with advanced disease at diagnosis, whereas, up to 80% relapse and the estimated median progression-free survival (PFS) is approximately 12-18 months. Increased knowledge on the molecular biology of EOC resulted in the development of several targeted therapies, including poly(ADP-ribose) polymerase (PARP) inhibitors. These agents have changed the therapeutic approach of the EOC and exploit homologous recombination (HR) deficiency through synthetic lethality, especially in breast cancer genes 1 and 2 () mutation carriers. Furthermore, wild-type patients with other defects in the HR repair pathway, or those with platinum-resistant tumors may obtain benefit from this treatment. While PARP inhibitors as a class display many similarities, several differences in structure can translate into differences in tolerability and antitumor activity. Currently, olaparib, rucaparib, and niraparib have been approved by Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for the treatment of EOC, while veliparib is in the late stage of clinical development. Finally, since October 2018 talazoparib is FDA and EMA approved for carriers with metastatic breast cancers. In this article, we explore the mechanisms of DNA repair, synthetic lethality, efficiency of PARP inhibition, and provide an overview of early and ongoing clinical investigations of the novel PARP inhibitors veliparib and talazoparib.
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http://dx.doi.org/10.21037/atm.2020.03.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812175PMC
December 2020

The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Scand J Clin Lab Invest 2021 04 21;81(2):160-165. Epub 2021 Jan 21.

Faculty of Medicine, Rheumatology Department, Gazi University Hospital, Ankara, Turkey.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.
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http://dx.doi.org/10.1080/00365513.2021.1871641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832453PMC
April 2021

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Turk J Med Sci 2021 08 30;51(4):1706-1711. Epub 2021 Aug 30.

Department of Internal Medicine, Faculty of Medicine, Osmangazi University, Eskişehir, Turkey

Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it’s hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood.

Materials And Methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files.

Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001.

Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.
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http://dx.doi.org/10.3906/sag-2011-74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569750PMC
August 2021

Serum defensin levels in patients with systemic sclerosis.

Adv Rheumatol 2020 12 22;60(1):54. Epub 2020 Dec 22.

Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc.

Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed.

Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34).

Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease.

Trial Registration: This study is not a clinical trial study.
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http://dx.doi.org/10.1186/s42358-020-00156-2DOI Listing
December 2020

Covid-19 scientific publications from Turkey

Turk J Med Sci 2021 06 28;51(3). Epub 2021 Jun 28.

Department of Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkey

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak poses a major global threat to the public health worldwide. The infectious disease caused by the virus that affected the entire world was named as the Coronavirus disease-2019 (COVID-19). The knowledge regarding the wide clinico-biological aspects of the COVID-19 continues to evolve very rapidly, given the growing data from all over the world. During this complicated process, healthcare professionals have benefited from each other’s experiences in combatting against the COVID-19 syndrome. COVID-19 related studies have been performed by a wide variety of research groups in Turkey as well as the rest of the world. The aim of this paper is to outline Turkish COVID-19 research indexed in the LitCovid system. LitCovid is a curated literature hub for tracking up-to-date scientific data about the SARS-CoV-2. COVID-19’s first case was detected in Turkey, on March 11th, 2020. Six months after the first case was observed, the total number of COVID-19 patients was reported to be as 286,455, and the total number of deaths due to SARS-CoV-2 was 6895. The genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Numerous drugs including lopinavir/ritonavir, favipiravir, neuraminidase inhibitors, remdesivir, umifenovir, azithromycin, and chloroquine have been suggested for the management of COVID-19 although the exact treatment is yet to be determined.
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http://dx.doi.org/10.3906/sag-2010-261DOI Listing
June 2021

Compliance of Familial Mediterranean Fever Patients With Regular Follow-up Visits and Associated Factors.

J Clin Rheumatol 2022 Jan;28(1):e77-e80

From the Division of Rheumatology, Department of Internal Medicine.

Background: Follow-up is crucial to detect asymptomatic complications of familial Mediterranean fever (FMF). The current European League Against Rheumatism recommendations state that patients with FMF should be evaluated at least every 6 months to monitor attacks, acute phase response, and proteinuria.

Objectives: This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors.

Methods: Adult patients with a diagnosis of FMF who had their initial visit at least over 1 year ago were included. Demographic and socioeconomic data, family history, and comorbid diseases were obtained from medical records. The International Severity Score for FMF and the Autoinflammatory Disease Damage Index scores were calculated. We defined patients as "compliant with follow-up visits" both if they had at least 2 visits during the previous year and a compatible physician's assessment. The characteristics of the compliant and noncompliant patients were compared, and multivariable logistic regression analysis was used to determine the factors influencing visit compliance.

Results: Four hundred seventy-four patients with FMF were included. Two hundred thirty (48.5%) were compliant, and 244 (51.5%) were noncompliant with follow-up visits. A family history of FMF in parents, the absence of a family history of FMF in siblings, treatment with biologic agents, concomitant medication use, multisite involvement during FMF attacks, and treatment satisfaction were independent predictors of visit compliance.

Conclusions: Only half of the patients with FMF were compliant with follow-up visits. Better strategies should be implemented to increase the compliance of FMF patients. Identifying independent predictors would help to build one.
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http://dx.doi.org/10.1097/RHU.0000000000001632DOI Listing
January 2022

Comparison of the effectiveness of pilates exercises, aerobic exercises, and pilates with aerobic exercises in patients with rheumatoid arthritis.

Ir J Med Sci 2021 Aug 22;190(3):1027-1034. Epub 2020 Oct 22.

Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Gazi University, Ankara, Turkey.

Background: Rheumatoid arthritis (RA) is a rheumatic disease characterized by erosive synovitis and polyarthritis. Exercise is known to improve many symptoms in RA patients.

Aim: This study was designed to compare the effects of pilates exercises, aerobic exercises, and combined training including pilates with aerobic exercises on fatigue, depression, aerobic capacity, pain, sleep quality, and quality of life.

Methods: Thirty voluntary RA patients were included in this study. Patients were divided into three groups equally, and treatment was applied to each group for 8 weeks. Pilates exercises were practiced to the first group, aerobic exercises were practiced to the second group, and combined training was performed to the third group. Fatigue, depression, aerobic capacity, pain, sleep quality, and quality of life were evaluated using Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), 6-minute walk test (6MWT), McGill Pain Questionnaire- Short Form (MPQ-SF), Pittsburg Sleep Quality Index (PSQI), and Rheumatoid Arthritis Quality of Life (RAQoL), respectively.

Results: The results of the present study showed significant improvements for the first group on fatigue, depression, aerobic capacity, and quality of life (p < 0.05). Improvements in all parameters except for pain were obtained for the second and third groups (p < 0.05). In addition, there was no statistically significant difference among the treatment groups in assessments (p > 0.05).

Conclusion: Pilates exercises may have similar effects to aerobic exercises in patients with RA. Addition of clinical pilates exercises to the routine treatment of RA may enhance the success of rehabilitation. Trial registration NCT03836820.
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http://dx.doi.org/10.1007/s11845-020-02412-2DOI Listing
August 2021

Determination of the Voice Parameters in Adult Individuals With Rheumatoid Arthritis and the Relation of Voice With Depression and Inflammation.

J Voice 2020 Oct 6. Epub 2020 Oct 6.

Gazi University, Faculty of Medicine, Department of Otolaryngology, Ankara, Turkey.

Objectives: To assess, through both objective and subjective methods, the complaints of dysphonia among adults with rheumatoid arthritis (RA). The secondary purpose of the study is to determine whether complaints of dysphonia are related to depression and disease activity.

Study Design: This is a prospective cohort study.

Methods: Eighty subjects (38 RA and 42 healthy volunteers aged 18-65 years old) were included in the study. Participants were evaluated using the Voice Handicap Index-10 (VHI-10) to assess voice complaints. Laryngeal findings of participants with RA were performed by videolaryngoscopy. Maximum phonation time (MPT) measurements and acoustic voice analysis (PRAAT software) were performed to evaluate the presence of objective dysphonia. Disease activity of individuals was calculated by using Disease Activity Score-28 (DAS-28) scale. Beck Depression Inventory (BDI) was applied to evaluate the symptoms of depression in participants.

Results: The prevalence of laryngeal symptoms of participants with RA was %42.1. According to the cut-off score of VHI-10, 15.8% of the participants in the study group had voice complaints. Comparing the MPT and acoustic voice analyses values of the study and control group, the MPT of the RA participants were statistically lower (P< 0.05). Perturbation parameters of male participants in the study and control groups were statistically different. 15.8% of participants in RA group had symptoms of depression. However, there was no statistically significant difference between BDI and acoustic voice parameters.

Conclusions: RA may be associated with voice disorders. Male patients with RA had worse jitter parameters, but the number of participants was low. Dysphonia may not be associated with depression and disease activity in RA patients.
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http://dx.doi.org/10.1016/j.jvoice.2020.09.014DOI Listing
October 2020

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

Cytokine 2021 01 29;137:155302. Epub 2020 Sep 29.

Gazi University, Faculty of Medicine, Hospital Rheumatology Department, Ankara, Turkey.

Background: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19.

Objective: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis.

Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed.

Results: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission.

Conclusions: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.
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http://dx.doi.org/10.1016/j.cyto.2020.155302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522034PMC
January 2021

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

Rheumatology (Oxford) 2021 01;60(1):333-339

Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Gazi University, Ankara.

Objective: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items.

Methods: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items.

Results: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency.

Conclusion: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.
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http://dx.doi.org/10.1093/rheumatology/keaa378DOI Listing
January 2021

Use of prognostic nutritional index in the evaluation of disease activity in patients with Behçet's disease.

Eur J Rheumatol 2020 Jul 21;7(3):99-104. Epub 2020 Jul 21.

Division of Rheumatology, Department of Internal Medicine, Gazi University School of Medicine, Ankara, Turkey.

Objective: Behçet's disease (BD) is a chronic, multisystem disorder that can cause severe morbidity and mortality. Monitoring tools that measure disease activity are required for effective management of BD. We aimed to investigate the association of prognostic nutritional index (PNI) with disease activity in BD.

Methods: In this cross-sectional study, we enrolled 88 adult patients with BD and 51 healthy controls. The patients were divided into patients with active and inactive BD according to their disease activities. PNI was calculated using the following formula: 10×serum albumin (g/dL)+0.005×peripheral lymphocyte count (per mm3). To evaluate BD activity, the Behçet Disease Current Activity Form was used. The relations of BD activity with PNI, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, erythrocyte sedimentation rate, and C-reactive protein were investigated. A receiver operator characteristic curve analysis was used to define the optimum cutoff value of PNI for active BD.

Results: A total of 48 patients were classified as having active BD and 40 as having inactive BD. Patients with active BD had lower mean PNI than patients with inactive BD and healthy controls (51.8±4.2, 57.4±2.9, and 56.6±3.6, respectively; p<0.001). In multivariate analysis, PNI was the only independent predictor of BD activity (odds ratio, -0.687; 95% confidence interval 0.548-0.861; p=0.001). The optimum cutoff of PNI for active BD was 55.35 with 79.2% sensitivity and 77.75% specificity.

Conclusion: PNI was significantly associated with BD activity. PNI may be a useful tool for the assessment of disease activity in BD.
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http://dx.doi.org/10.5152/eurjrheum.2020.20010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431357PMC
July 2020

Factors associated with damage in patients with familial Mediterranean fever.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):42-48. Epub 2020 Jun 18.

Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey.

Objectives: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage.

Methods: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes.

Results: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score.

Conclusions: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.
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December 2020

Modified Glasgow Prognostic Score, Prognostic Nutritional Index and ECOG Performance Score Predicts Survival Better than Sarcopenia, Cachexia and Some Inflammatory Indices in Metastatic Gastric Cancer.

Nutr Cancer 2021 9;73(2):230-238. Epub 2020 Apr 9.

Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.

Gastric carcinoma (GC) patients usually present with locally advanced or metastatic disease; therefore treatment aim is mainly palliation. In this study our purpose is to analyze the prognostic values of the sarcopenia index (SI), cachexia index (CIn) and other inflammatory indexes (advanced lung cancer inflammation index [ALI], modified Glasgow Prognostic Score [mGPS], prognostic index [PI], prognostic nutritional index [PNI] and neutrophil-to-lymphocyte ratio [NLR]) in metastatic GC patients. Data from the files of metastatic GC patients, who applied to Medical Oncology outpatient clinic in Marmara University Pendik Education and Research Hospital between January 2011 and June 2016, were retrospectively reviewed. Five hundred seventy patients with gastric cancer were detected. Exclusion criteria were the inability to reach the patient surveys for prognostic index calculations, the presence of additional comorbidities to affect the laboratory parameters, and the absence of metastatic disease. Finally, 87 of these patients were included in this study. For SI calculation L3 level muscle area was measured from patients' computed tomography (CT) by a radiologist. SI reference value was obtained from western-EGWSOP (The European Working Group on Sarcopenia in Older People) and eastern (Harada Y, et al.) sources separately, as Turkey doesn't have a reference value for SI. NLR cutoff value was accepted as the median value of patients' NLR measurements. Statistical analysis was conducted using SPSS. Kaplan-Meier and Cox regression models were used to assess independent prognostic factors. The area under the curve was used to compare the prognostic value of indexes. The median length of follow-up of 87 patients was nine months (1-64 mo,/s), and 78 patients died during follow-up. Fifty-nine patients were male (63%), and the median age was 62 (range, 23-88). According to univariate analysis high mGPS and PI score, PNI level <45, NLR level ≥ 3.41, ALI level <18, CI level under 35, SI (Harada Y, et al) ≤44.5 for males and ≤36.5 for females, ECOG score ≥ 2, weight loss more than 10% during last 6 mo, BMI under 24 were poor prognostic factors. Age, gender, having multiple organ metastasis, history of gastric surgery, positivity C-erb-B2, SI (EGWSOP) ≤52.4 for males, and ≤38.4 for females did not have any impact on survival. According to multivariate analysis, high mGPS (score 2) (HR 2,494, 95% CI 1.25-4 .94,  = 0.02), PNI (score 1) (HR 4.2, 95% CI 1.73-10.1,  < 0.001) and ECOG score (≥2) (HR 1.541, 95% CI 1,089-4,214,  = 0.004) have been found to be independent prognostic factors which are determining the survival. mGPS was found to be more valuable than other indexes for predicting mortality by measuring the AUC with ROC analysis. In our study, mGPS, PNI and ECOG score were independent indicators for shorter survival in metastatic gastric cancer patients. mGPS and PNI, which can be done by using only serum CRP, albumin level and complete blood count, might be inexpensive, practical and beneficial to use in routine clinical practice to determine survival.
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http://dx.doi.org/10.1080/01635581.2020.1749290DOI Listing
August 2021

Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography for the Evaluation of Patients With Inflammation of Unknown Origin.

J Clin Rheumatol 2021 Sep;27(6):219-225

From the Division of Rheumatology, Department of Internal Medicine.

Background: Sometimes, the underlying causes of inflammation cannot be established despite meticulous investigation, including medical history, physical examination, laboratory tests, and radiologic procedures. Rheumatologists are often faced with patients whose condition is known as inflammation of unknown origin (IUO). Differential diagnosis of IUO is diverse, and investigation of these cases is challenging and time-consuming.

Objective: The study aimed to assess the diagnostic role of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with IUO.

Methods: The study sample consisted of 97 adult patients with IUO who have not been previously diagnosed with an infectious, inflammatory, or malignant disease. The necessary data were collected from January 2015 to June 2018 with a 6-month follow-up period. The patients were screened using PET/CT after a specific diagnosis could not be established with detailed laboratory and radiologic evaluations.

Results: A final diagnosis was established at follow-up, and 47 (54%) of the 97 patients had inflammatory diseases, 30 (34.4%) had malignancies, and 10 (11.4%) had infections. Despite meticulous investigation, 10 patients were left undiagnosed in the follow-up. PET/CT aided diagnosis in 59 patients (60.8%), but it was not helpful in 38 patients (39.2%). PET/CT was positive in 30 (63%) of the 47 patients with inflammatory diseases, whose final diagnosis was inflammatory rheumatic disease, as follows: large-vessel vasculitis in 19 patients, polymyalgia rheumatica in 7 patients, and seronegative arthritis or other rare miscellaneous diseases in 4 patients. The sensitivity of PET/CT was 67% with a specificity and diagnostic accuracy of 100% and 71%, respectively.

Conclusions: Investigation of the underlying etiology of IUO is time-consuming and challenging. PET/CT may help identify the final diagnosis more quickly by locating an obscure inflammatory site; thus, it may reduce the number of unnecessary biopsies, diagnostic time, anxiety, work loss, morbidity, and mortality.
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http://dx.doi.org/10.1097/RHU.0000000000001297DOI Listing
September 2021

Hepatoid adenocarcinoma of the lung and the review of the literature.

J Oncol Pharm Pract 2020 Sep 10;26(6):1505-1510. Epub 2020 Feb 10.

Department of Nuclear Medicine, Istanbul Oncology Hospital, Istanbul, Turkey.

Introduction: Hepatoid adenocarcinoma of the lung is an extremely rare type of the non-small cell lung cancer. Treatment principles and prognosis are similar to that of lung adenocarcinoma.

Case Report: A 62-year-old female smoker presented with a huge mass in the left upper lobe. After diagnostic biopsy, she underwent left pneumonectomy and mediastinal lymph node dissection. A diagnosis of stage T4N1M0 hepatoid adenocarcinoma of the lung with positive surgical margins was made.

Management And Outcome: After the operation, the level of serum alpha fetoprotein was 9010 ng/ml (N: <10). The level of serum alpha fetoprotein was decreased with concurrent chemoradiotherapy and chemotherapy. Disease progression was detected at 11 months after diagnosis. No response was obtained to other therapies. The patient died at 14 months from the time of diagnosis.

Discussion: Usually, patients with hepatoid adenocarcinoma of the lung are male smokers. Hepatoid adenocarcinoma tends to settle in the upper lobes of the lung. The most important prognostic factor of the hepatoid adenocarcinoma of the lung is the disease stage at the diagnosis and patients with metastatic disease have poor survival.
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http://dx.doi.org/10.1177/1078155220903360DOI Listing
September 2020

Does metformin affect mammographic breast density in postmenopausal women with type 2 diabetes.

Gynecol Endocrinol 2020 Sep 10;36(9):800-802. Epub 2020 Feb 10.

Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey.

Increased mammographic breast density (MBD) is known to be associated with an increased risk of developing breast cancer. In this study, we aimed to research the possible relationship between MBD and metformin use in postmenopausal women diagnosed with type 2 diabetes mellitus (T2DM). The patients were divided into two groups: women with T2DM and who were on metformin and women who were newly diagnosed with T2DM and had not yet taken metformin. MBD types are evaluated by a specialist radiologist. Among the 74 women, 32 (43.2%) were in the group that did not use metformin and 42 (56.8%) were in the group of patients using metformin. The duration of breastfeeding ( = .0003), fasting blood glucose ( = .0003) and HbA1c ( = .0006) were statistically significantly higher in the group not using metformin. The quantitative mean ranks of the group members' MBD's were 41.81 in the metformin naïve group and 34.21 in the group using metformin ( = .12). In conclusion, metformin has no statistically significant effect on MBD in postmenopausal female patients with T2DM.
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http://dx.doi.org/10.1080/09513590.2020.1725972DOI Listing
September 2020

Platelet/lymphocyte ratio and mean platelet volume in patients with granulomatosis with polyangiitis.

Adv Rheumatol 2019 12 31;60(1). Epub 2019 Dec 31.

Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Gazi University, Ankara, Turkey.

Background: Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody is a valuable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) has been regarded as a potential marker in assessing systemic inflammation. We aimed to explore the value of PLR and MPV in the assessment of disease activity and manifestations of disease in GPA.

Methods: 56 newly diagnosed GPA patients and 53 age-sex matched healthy controls were included in this retrospective and cross-sectional study with comparative group. Complete blood count was performed with Backman Coulter automatic analyzer, erythrocyte sedimentation rate (ESR) with Westergen method and C-reactive protein (CRP) levels with nephelometry. The PLR was calculated as the ratio of platelet and lymphocyte counts.

Result: Compared to control group, ESR, CRP and PLR were significantly higher and MPV significantly lower in GPA patients. In patients group, PLR was positively correlated with ESR and CRP (r = 0.39, p = 0.005 and r = 0.51, p < 0.001, respectively). MPV was negatively correlated with ESR and CRP (r = - 0.31, p = 0.028 and r = - 0.34 p = 0.014, respectively). Patients with renal involvement had significantly higher PLR than patients without renal involvement (median:265.98, IQR:208.79 vs median:180.34 IQR:129.37, p = 0.02). PLR was negatively correlated with glomerular filtration rate (r = - 0.27, p = 0.009). A cut-off level of 204 for PLR had 65.6% sensitivity and 62.5 specificity to predict renal involvement.

Conclusion: PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA.
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http://dx.doi.org/10.1186/s42358-019-0110-8DOI Listing
December 2019

Monocyte to Lymphocyte Ratio, Neutrophil to Lymphocyte Ratio, and Red Cell Distribution Width are the Associates with Gouty Arthritis.

Acta Medica (Hradec Kralove) 2019 ;62(3):99-104

Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey.

Background: Neutrophils, monocytes, and macrophages activations are associated with a gout attack. Monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), red cell distribution width (RDW), and mean platelet volume (MPV) are well-known inflammation markers. In this study, we aimed to investigate whether they could be a predictive marker to the gout attack.

Material And Methods: A hundred and ten gout patients (male/female, 86/24) and 90 (male/female, 64/26) age-, gender-, and body mass index-matched volunteer controls were included in the study. Blood samples were obtained in the intercritical and attack period of the patients. Hemogram, serum uric acid (SUA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were studied.

Results: In the attack period NLR (p < 0.001), PLR (p < 0.05), MLR (p < 0.001), RDW (p < 0.05), MPV (p < 0.05), ESR (p < 0.001), CRP (p < 0.001) and SUA (p < 0.001) values were significantly higher than intercritical period values. According to the results of regression analysis; There was an independent strong relationship between the gout attack and SUA, (Beta [β] = 0.352, p < 0.001), ESR (β = 0.329, p < 0.001), CRP (β = 0.286, p < 0.001), MLR (β = 0.126, p < 0.001), RDW (β = 0.100, p = 0.003) and NLR (β = 0.082, p = 0.014).

Conclusions: MLR, RDW, and NLR may be a strong predictive marker for a gout attack. MPV and PLR values in the gout attack may be associated with systemic inflammation.
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http://dx.doi.org/10.14712/18059694.2019.132DOI Listing
April 2020
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