ISSN 2149-2042 | e-ISSN 2149-4606
Volume : 40 Suppl : 4 Year : 2025
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Medeniyet Medical Journal - Medeniyet Med J: 40 (4)
Volume: 40  Issue: 4 - 2025
1. Cover

Page I

ORIGINAL ARTICLE
2. Sedentary Behavior Worsens the Adverse Impact of E-cigarettes Smoking on Sleep Quality
Mahmoud Awad ALOMARI, Omar Falah KHABOUR
doi: 10.4274/MMJ.galenos.2025.82754  Pages 202 - 208
Objective: Sleep is vital for homeostasis. Smoking negatively affects sleep quality, whereas regular physical activity and reduced sedentary behavior improve sleep quality. However, the combined effect of e-cigarettes, physical activity, and sedentary behavior remains unknown. Therefore, the current study compared sleep quality according to e-cigarette dependence status among adults with high versus low levels of physical activity and sedentary behavior.
Methods: In 644 adults, sleep, e-cigarette dependence, physical activity, and sedentary behavior were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Penn State E-Cigarette Dependence Index, and the International Physical Activity Questionnaire, respectively.
Results: The two-way ANCOVA, after controlling for gender, income, and disease status, revealed main effects of e-cigarette dependence (p<0.001) and sedentary behavior (p<0.03), and an interaction effect (p<0.05) on the PSQI. Post hoc comparisons showed significantly greater PSQI scores among adults with heavy e-cigarette dependence and in the high sedentary behavior group (p<0.05). However, the analysis showed no main effect of physical activity on PSQI scores (p>0.05).
Conclusions: The results suggest that heavy dependence on e-cigarettes negatively alters sleep quality. These adverse sleep alterations are exacerbated by sedentary behavior. Programs are needed to reduce e-cigarette use and sedentary behavior to enhance sleep quality.

3. Prenatal Exposure to 3.5 GHz Radiofrequency Radiation and Long-Term Skin Histomorphometry: An 18-Month Experimental Rat Study
Elif GELENLI DOLANBAY, Tugay MERT, Reyhan Nur KURTOGLU, Unal USLU, Suleyman DASDAG
doi: 10.4274/MMJ.galenos.2025.48323  Pages 209 - 216
Objective: This study aimed to evaluate long-term skin histomorphometry at 18 months postpartum in rats exposed in utero to 3.5 GHz radiofrequency radiation (RFR).
Methods: Pregnant Wistar Hannover rats were exposed to Global System for Mobile Communications-modulated 3.5 GHz RFR for 2 h/day throughout gestation, while the sham group underwent mock exposure. Offspring (n=5 per group) were not exposed to any further RFR until 18 months after birth. Dorsal skin samples were stained with hematoxylin–eosin and Masson’s trichrome, and dermal thickness, adipose tissue area, dermal area, adipose/dermis ratio, and fat percentage were quantified. Specific absorption rate (SAR) was calculated using CST Studio Suite. Data were analyzed using the Student’s t-test or the Mann-Whitney U test. Statistical significance was defined as p<0.05.
Results: The peak spatial SAR (psSAR) values were 0.06622 mW/g (for 1 g) and 0.03825 mW/g (for 10 g). No statistically significant differences were observed between RFR-exposed and sham groups in dermal thickness (655.32±87.46 μm vs 544.42±135.01 μm); fat area percentage (0.73±0.29% vs 0.66±0.22%); dermal area (1.05±0.17 vs 0.88±0.22); adipose/dermis ratio (1.78 ± 0.24 vs 1.54±0.28); or fat percentage (40.04±11.78% vs 42.96±11.60%) (all p>0.05).
Conclusions: Prenatal exposure to 3.5 GHz RFR did not cause significant skin histomorphometric alterations in the dermis of aged female rats. The skin’s barrier properties, regenerative capacity, and repair mechanisms may mitigate long-term structural effects of such exposures.

4. Surgical Success and Predictive Factors for Residual Stones Following Supine Percutaneous Nephrolithotomy in the Galdakao-Modified Valdivia Position
Gunal OZGUR, Ersin GOKMEN, Yiloren TANIDIR, Kamil CAM, Tarik Emre SENER
doi: 10.4274/MMJ.galenos.2025.59265  Pages 217 - 225
Amaç: Supin perkütan nefrolitotomi (sPCNL), böbrek taşlarının tedavisinde güvenli ve etkili bir tedavi yöntemidir. Bu çalışmada, Galdakao-modifiye Valdivia pozisyonunda (GMV-sPCNL) uygulanan sPCNL sonrası cerrahi sonuçların değerlendirilmesi ve rezidüel fragmanları öngören faktörlerin belirlenmesi amaçlanmıştır.
Yöntemler: GMV-sPCNL uygulanan hastalara ait klinik veriler retrospektif olarak incelendi. Çalışmanın birincil sonucu taşsızlık ve komplikasyon oranlarının saptanmasıdır. Rezidü taş varlığına göre hastaların demografik, radyolojik ve perioperatif parametreleri karşılaştırıldı.
Bulgular: Çalışmaya 195 hasta [Erkek: 127 (%65.1)/Kadın: 68 (%34.9)]dahil edildi. Ortalama yaş 48,6 (±15,6) yıl, ortalama beden kitle indeksi (BKİ) 27,4 (±5) kg/m2 idi. Genel taşsızlık oranı %83,1 olarak saptandı. Rezidü taş varlığı; daha yüksek taş yükü (taş sayısı, boyutu, yüzey alanı ve hacmi), daha uzun operasyon süresi ve uzamış hastanede yatış süresi ile ilişkili bulundu (p<0,05). Cinsiyet, yaş, BKİ, cerrahi tarafı ve taş dansitesi ile taşsızlık arasında anlamlı bir ilişki saptanmadı. Receiver operating characteristic analizinde, taş sayısının 2’den fazla olması, taş boyutunun ≥26 mm ve taş hacminin ≥2639,8 mm3 olması rezidüel fragmanları anlamlı şekilde öngördü. Taş hacmi, en iyi öngörü performansını göstermiş olup, buna karşılık gelen duyarlılık ve özgüllük değerleri sırasıyla %81,8 ve %61,0 olarak bulunmuştur. GMV-sPCNL hastalarında düşük komplikasyon oranları gözlendi. Hastaların %86,2’sinde hiç komplikasyon görülmedi veya sadece minör olaylar yaşandı. Majör komplikasyon (Clavien-Dindo ≥3) oranı ise %4,6 olarak saptandı.
Sonuçlar: GMV-sPCNL, yüksek taşsızlık ve düşük komplikasyon oranları ile büyük böbrek taşlarında etkili bir tedavi seçeneğidir. Taş yükü parametreleri —taş sayısı, boyutu ve hacmi— cerrahi başarının önemli belirleyicileri olarak saptandı.

5. Serum Interleukin-40 and Soluble CD40 Ligand as Complementary Biomarkers for Disease Activity in Multiple Sclerosis Patients
Mustafa Ziyad NEAMAH, Inas K SHARQUIE, Gheyath AL GAWWAM
doi: 10.4274/MMJ.galenos.2025.48830  Pages 226 - 234
Objectives: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system for which reliable biomarkers of disease activity remain an unmet need. Interleukin-40 (IL-40) and soluble CD40 ligand (sCD40L) have been proposed to play roles in the pathogenesis of autoimmune diseases. This study aimed to evaluate serum levels of IL-40 and sCD40L as biomarkers of disease activity in MS patients, and to compare their diagnostic and monitoring performance between MS patients and healthy controls.
Methods: One hundred twenty MS patients were recruited from the Department of MS at the Baghdad Teaching Hospital and divided into two groups based on disease status: active (n=60) and inactive (n=60). Additionally, 57 matched healthy individuals were included as controls. A sandwich enzyme-linked immunosorbent assay was used to measure the serum levels of IL-40 and sCD40L in blood samples from each participant.
Results: Both active and inactive patient cohorts showed significantly higher serum levels of IL-40 (44.25±8.57 ng/mL and 38.98±11.31 ng/mL, respectively) compared with their control group (20.82±14.27 ng/mL) (p=0.005). Likewise, sCD40L concentrations were elevated in both active (2155.59±587.02 pg/mL) and inactive (1885.23±851.32 pg/mL) patients compared with controls (849.79±341.87 pg/mL; p=0.0006). IL-40 correlated positively with sCD40L (r=0.399, p=0.005). The receiver operating characteristic analysis showed high diagnostic performance for IL-40 (area under the curve =0.873; sensitivity 87.5%; specificity 76.7%) and sCD40L (area under the curve =0.901; sensitivity 92.5%; specificity 81.7%).
Conclusions: Both IL-40 and sCD40L are significantly elevated in MS and exhibit promising diagnostic validity. These biomarkers may serve as complementary tools for monitoring MS disease activity and progression, offering potential value in clinical practice and therapeutic decision-making.

6. Machine Learning-Based Analysis of Serum Interleukin-39 and Interleukin-40 Levels for Differentiating Rheumatoid Arthritis and Systemic Lupus Erythematosus
Inas K. SHARQUIE, Faiq Isho GORIAL, Zahraa Adnan AL-GHURAIBAWI, Amal Mahdi AL RUBAYE
doi: 10.4274/MMJ.galenos.2025.95690  Pages 235 - 240
Amaç: Romatoid artrit (RA) ve sistemik lupus eritematozus (SLE), bağışıklık düzensizliği ve sistemik enflamasyon ile karakterize edilen ciddi otoimmün hastalıklardır. Tanı araçlarındaki gelişmelere rağmen klinik belirtilerin birbiriyle örtüşmesi nedeniyle RA'yı SLE'den ayırt etmek hala zordur. Ortaya çıkan kanıtlar, interlökin-39 [(IL)-39] ve IL-40 gibi yeni sitokinlerin otoimmün patogenezdeki potansiyel rollerini vurgulamaktadır. Bu çalışma, çeşitli makine öğrenimi (ML) algoritmaları kullanarak RA ile SLE’yi ayırt etmek için serum IL-39 ve IL-40 düzeylerinin tanısal yararını değerlendirmeyi amaçlamıştır.
Yöntemler: RA’lı 66 hasta ve SLE’li 66 hastadan elde edilen veriler, daha önce yayınlanmış serum IL-39 ve IL-40 veri setleri kullanılarak analiz edilmiştir. Lojistik regresyon, rastgele orman, karar ağacı ve destek vektör makinesi gibi ML algoritmaları uygulandı. Model performansı, duyarlılık, doğruluk, özgüllük ve alıcı işletim karakteristik eğrisi altındaki alan kullanılarak değerlendirildi.
Bulgular: SLE hastaları, RA hastalarına göre anlamlı olarak daha yüksek serum IL-39 ve IL-40 düzeyleri sergiledi (p<0,001). Rastgele orman modeli %92,4 doğruluk ve 0,95 AUC elde etti. Özellik önem analizi, IL-39 ve IL-40’ın sınıflandırma performansına sırasıyla %58 ve %42 katkıda bulunduğunu ortaya koydu.
Sonuçlar: IL-39 ve IL-40 serum düzeylerine dayalı ML modelleri, RA’yı SLE’den etkili bir şekilde ayırt edebilir. Bulgular, yapay zeka tabanlı analitik yaklaşımların yeni sitokin biyobelirteçleriyle entegre edilmesinin, otoimmün hastalıklarda tanı doğruluğunu artırabileceğini ve ayırıcı tanıyı destekleyebileceğini göstermektedir.

7. Evaluation of the Combined Effects of Rosmarinic Acid and Cisplatin in Gastric Cancer Cells
Ceren SARI, Ceren SUMER, Saniye KOC ADA, Burcu YUCEL
doi: 10.4274/MMJ.galenos.2025.47041  Pages 241 - 249
Objective: Gastric cancer remains a significant global health concern, necessitating investigation into more effective treatment approaches. This study investigates the combined effects of rosmarinic acid, a polyphenolic compound with known anticancer properties, and cisplatin, a conventional chemotherapeutic agent, on human gastric carcinoma (HGC-27) cells.
Methods: Cell viability was evaluated at different concentrations for rosmarinic acid and cisplatin, and inhibitory concentration (IC)50, IC30, and IC10 values were subsequently determined. IC30 and IC10 doses were selected for combination experiments. Thiazolyl Blue Tetrazolium Bromide assay, colony formation assay, in vitro scratch assay, and 3D tumor spheroid growth assay were performed to evaluate the effects of individual and combined treatments.
Results: Rosmarinic acid and cisplatin individually reduced cell viability in a dose-dependent manner. Both the IC10 and IC30 dose combinations of the two agents demonstrated significant inhibitory effects on colony formation and cell motility, indicating an additive interaction compared with the control and the individual treatments. The combined treatment also inhibited spheroid growth, although the extent of the reduction was similar to that observed with the individual agents.
Conclusions: This study provides initial insights into the potential efficacy of the rosmarinic acid-cisplatin combination. The combination of these agents reduced cell viability, colony formation, and cell motility. The increased cytotoxicity observed in 2D models was not evident in 3D spheroid models, highlighting the importance of 3D systems that more accurately mimic the complex structure of tumors. This finding suggests that differences in drug sensitivity between 2D and 3D models should be considered when evaluating combination therapies.

8. Safety Profile of Roxadustat in Anemic Patients: A Meta-Analysis of 21 RCTs
Lokman Hekim TANRIVERDI, Ahmet SARICI, Mehmet Ali ERKURT, Hacı Bayram BERKTAS
doi: 10.4274/MMJ.galenos.2025.44045  Pages 250 - 261
Objective: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor used to treat anemia in patients with chronic kidney disease. We aimed to assess its safety and tolerability profile through a meta-analysis of randomized controlled trials (RCTs).
Methods: A systematic search of the Cochrane CENTRAL, Ovid Medline R, PubMed, and Web of Science databases was conducted up to January 1, 2025 was conducted. RCTs comparing roxadustat with control groups were included. Inverse-variance-weighted random-effects models were used. The primary outcome was the risk of any serious treatment-emergent adverse event (TEAE). Subgroup analyses were based on etiology, comparator, and prior erythropoiesis-stimulating agent (ESA) use.
Results: Twenty-one RCTs involving 11.686 patients were included. Roxadustat was not associated with a higher risk of any serious TEAE compared with placebo [risk ratio (RR) =1.37, 95% confidence interval (CI): 0.79-2.37] or with ESA (RR=1.05, 95% CI: 0.99-1.10). Similarly, cardiac serious adverse events (SAEs) did not differ significantly when compared with ESA (RR=1.11, 95% CI: 0.75-1.12) or placebo (RR=1.11, 95% CI: 0.92-1.35). Hyperkalemia incidence was significantly higher compared with placebo (RR=1.25, 95% CI: 1.02-1.53) but not compared with ESA (RR=1.03, 95% CI: 0.77-1.36). There were also no significant differences in the incidence of serious infections (RR=0.74, 95% CI: 0.21-2.59), azotemia (RR=0.96, 95% CI: 0.46-2.00), hypertension (RR=1.06, 95% CI: 0.93-1.21), or pneumonia (RR=0.96, 95% CI: 0.81-1.14) compared with ESA. Notably, withdrawal due to adverse events (RR=2.11, 95% CI: 1.59-2.79) was significantly higher compared with ESA. TEAEs leading to death were similar compared with ESA (RR=0.98, 95% CI: 0.85-1.13) but were increased compared with placebo (RR=1.21, 95% CI: 1.04-1.42). All-cause mortality was significantly lower than with placebo (RR=0.40, 95% CI: 0.28-0.57) but was similar to ESA (RR=0.89, 95% CI: 0.57-1.37). Subgroup analyses for the primary outcome by etiology and prior ESA use were not consistent with the main findings.
Conclusions: Roxadustat demonstrated a SAE profile generally comparable to that of ESA, with no significant differences in cardiac SAEs, serious infections, azotemia, hypertension, or pneumonia. Hyperkalemia was more frequent compared with placebo, and withdrawals due to adverse events were more frequent compared with ESA. TEAEs leading to death were similar to ESA but higher than with placebo, whereas all-cause mortality was lower than with placebo and comparable to ESA. Taken together, current evidence supports the overall non-inferiority of roxadustat to ESA in terms of safety.

9. Serum Podocalyxin Level as a Potential Biomarker for Diagnosis of Nephrotic Syndrome and Prediction of Steroid Response
Emre LEVENTOGLU, Mustafa SORAN, Ummugulsum CAN
doi: 10.4274/MMJ.galenos.2025.15043  Pages 262 - 268
Objective: Idiopathic nephrotic syndrome (NS) is a common pediatric glomerular disorder. Podocyte damage constitutes a central mechanism in its pathophysiology. Podocalyxin, a major sialoglycoprotein expressed on podocytes, has been found to be elevated in urine samples from patients with glomerular diseases. However, its potential role in serum and its association with steroid responsiveness in NS remain unexplored.
Methods: This observational study included 17 children diagnosed with NS and age-matched controls without kidney pathology. Serum podocalyxin levels were measured at diagnosis using enzyme-linked immunosorbent assay. Patients received standard corticosteroid therapy at a dose of 2 mg/kg/day for four weeks, followed by a gradual taper. Based on clinical response, patients were classified as steroid-sensitive or steroid-dependent NS (SDNS). Serum podocalyxin levels were compared between patients and controls, and among subgroups based on treatment response.
Results: Serum podocalyxin levels were significantly higher in NS than in the control group [1.87 ng/dL [interquartile range (IQR: 0.87)] vs. 1.54 ng/dL (IQR: 0.29), p=0.031]. All patients initially achieved remission with corticosteroids; however, six patients subsequently developed SDNS. Among these, 4 responded to calcineurin inhibitors, while 2 required rituximab to achieve remission. Current results indicate that serum podocalyxin levels do not provide sufficient predictive value for estimating steroid response or disease course. No significant correlations were found between podocalyxin levels and other laboratory parameters.
Conclusions: Serum podocalyxin levels are elevated in pediatric NS and may reflect the degree of podocyte injury. However, current findings indicate that serum podocalyxin levels are insufficient for predicting disease severity or steroid response. Additional studies involving larger patient cohorts are needed to further substantiate findings.

10. The Effect of Flow-Controlled Ventilation on Mechanical Power in Laparoscopic Surgeries: A Comparative Analysis with Pressure Controlled Volume Guaranteed and Volume Controlled Ventilation
Ayse SENCAN, Nurseda DUNDAR, Bedirhan GUNEL, Ahmet YUKSEK
doi: 10.4274/MMJ.galenos.2025.66664  Pages 269 - 277
Objective: To compare mechanical power (MP) levels among flow-controlled ventilation (FCV), volume-controlled ventilation (VCV), and pressure-controlled volume-guaranteed ventilation (PCV-VG) during laparoscopic surgery and to test the hypothesis that the stable flow dynamics of FCV would reduce MP.
Methods: Patients were divided into three groups according to the mechanical ventilation modes applied during laparoscopic surgery: PCV-VG (n=15), VCV (n=14), and FCV (n=15). MP was calculated at four timepoints: baseline (T1), post-induction (T2), during CO2 insufflation (T3), and post-insufflation (T4). The primary outcome of the study was the comparison of MP in the FCV mode with MP in the other groups during insufflation. Driving pressure (DP), plateau pressure, and peak airway pressure were also analyzed.
Results: Baseline MP was highest in PCV-VG (6.9 J/min vs. 5.0 J/min in VCV and 5.1 J/min in FCV; p=0.002). During insufflation (T3), MP increased to a similar extent across groups (PCV-VG: 9.4 J/min, VCV: 8.7 J/min, FCV: 8.6 J/min), with PCV-VG showing the smallest relative rise (p<0.001). DP and plateau pressures increased during pneumoperitoneum, but Bonferroni-adjusted comparisons revealed that these were not statistically significant. PCV-VG maintained higher positive end-expiratory pressure (5 vs. 4 cmH2O, p<0.001); however, it did not significantly affect peak pressures.
Conclusions: Contrary to our hypothesis, FCV did not reduce MP more effectively than either VCV or PCV-VG. However, PCV-VG demonstrated better mitigation of insufflation-induced increases in MP, suggesting potential advantages for lung protection during laparoscopy. Further prospective studies are needed to assess clinical outcomes.

LETTERS TO THE EDITOR
11. Right Coronary Artery Perforation with Subsequent Graft Stent Embolization to the Left Main Coronary Artery: It Never Rains but It Pours!
Efe YILMAZ, Furkan KARAHAN, Çağlar KAYA, Kenan YALTA
doi: 10.4274/MMJ.galenos.2025.89021  Pages 278 - 279
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INDEX
12. 2025 Referee Index

Page E1
Abstract |Full Text PDF