Karatas, Ezgi; Yavuzer, Bulent; Koksaldi, Seher; Kayabasi, Mustafa; Sezgin, Esra Tuba; Sarigul, Cengiz; Demir, Ozlem; Suleyman, Bahadir; Suleyman, Halis

Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy.

Binay, Umut Devrim; Karakeçili, Faruk; Barkay, Orçun; Kuru, Betül

Background and Objectives: Accurate assessment of liver fibrosis is essential for treatment decisions in patients with chronic hepatitis B (CHB). Although liver biopsy is considered the reference standard, its invasive nature limits routine use. Serum-based non-invasive fibrosis scores have been proposed as alternatives; however, their diagnostic performance in CHB remains variable. This study aimed to compare multiple serum-based non-invasive fibrosis scores with liver biopsy findings and to evaluate their association with histological activity. Materials and Methods: This retrospective cross-sectional study included 219 adult patients with CHB who underwent liver biopsy with simultaneous laboratory evaluation. Patients with viral co-infections (HIV, HCV, or HDV), metabolic syndrome, diabetes mellitus, hepatic steatosis, or incomplete data were excluded. Non-invasive fibrosis scores—including APRI, FIB-4, AST/ALT ratio (AAR), age–platelet index (API), GGT-to-platelet ratio (GPR), Lok index, modified Forns index, Albumin–Bilirubin (ALBI) score, and red cell distribution width (RDW)-based indices—were calculated using routine laboratory parameters. Histopathological fibrosis staging served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and areas under the curve (AUC) were compared using the DeLong test. Associations with histological activity index (HAI) were assessed using Spearman correlation. Results: For the prediction of significant fibrosis (≥F2), FIB-4 demonstrated the highest AUC, followed by ALBI and APRI. For advanced fibrosis (≥F3), FIB-4 again showed the highest AUC, followed by APRI and GPR. For significant fibrosis (≥F2), DeLong analysis revealed no statistically significant differences between FIB-4 and the other serum-based scores (p > 0.05). APRI (r = 0.556, p < 0.001) and FIB-4 (r = 0.463, p < 0.001) showed the strongest correlations with HAI. In ROC analysis for moderate-to-severe histological activity (HAI ≥ 4), APRI demonstrated the highest diagnostic accuracy (AUC = 0.677). Conclusions: Serum-based non-invasive fibrosis scores demonstrate comparable but overall modest diagnostic performance for biopsy-confirmed fibrosis in patients with chronic hepatitis B. Indices such as FIB-4 and APRI demonstrated relatively better discrimination and may be considered as screening or rule-out tools in selected clinical contexts. APRI and FIB-4 also show associations with histological activity; however, their clinical application should be interpreted with caution, given their moderate discriminatory capacity.

Barkay, Orçun; Keskin, Ercüment

Background and Objectives: Intravesical Bacillus Calmette-Guérin (BCG) therapy remains a cornerstone in the treatment of non-muscle-invasive bladder carcinoma due to its efficacy in reducing recurrence and progression rates. However, its use is associated with various complications—including urinary tract infections (UTIs)—which necessitates further exploration. This study aims to analyze UTIs occurring during intravesical BCG treatment, emphasizing the microbial spectrum, resistance patterns, and risk factors from an infectious diseases and clinical microbiology perspective. Materials and Methods: A retrospective analysis was conducted on 240 patients diagnosed with non-muscle-invasive bladder carcinoma who received intravesical BCG therapy between 2010 and 2021. Data were collected from hospital records, including demographic characteristics, comorbidities, number of intravesical BCG cycles, and microbiological findings. UTIs were classified based on susceptibility patterns, and statistical analyses were performed to determine associations between clinical variables and UTI risk. Results: UTIs developed in 39.1% (n = 94) of patients, with 25.8% (n = 62) caused by susceptible pathogens and 13.3% (n = 32) by resistant pathogens. The most common causative agent was Escherichia coli (80.7% in susceptible UTIs, 43.8% in resistant UTIs), followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The presence of diabetes mellitus and chronic kidney disease significantly increased the risk of developing a UTI (p < 0.05). A higher number of intravesical BCG cycles correlated with increased UTI occurrence (p < 0.001). Serum C-reactive protein (CRP) levels were significantly elevated in patients with resistant UTIs, while procalcitonin levels were not a reliable predictor of UTI occurrence. Conclusions: Intravesical BCG therapy is associated with a significant incidence of UTIs, particularly among patients with predisposing comorbidities. The increasing prevalence of antibiotic-resistant infections underscores the need for careful monitoring and targeted antimicrobial stewardship strategies. CRP may serve as a useful adjunctive marker for UTI diagnosis in this setting. Future studies should focus on optimizing infection control measures and refining diagnostic criteria to differentiate between BCG-related inflammation and infectious complications.

Taş, Necip Gökhan; Aktaş, Osman; Taş, Hakan Gökalp; Zırh, Selim; Kurt, Nezahat; Uslu, Hakan

Background and Objective: Probiotics have been shown to be effective in controlling various adverse health conditions such as antibiotic-associated diarrhea, inflammatory bowel disease, obesity, and neurological diseases. However, to our knowledge, there is no research on the preventive effect of probiotics on heart damage caused by infections. This study examined the preventive benefits of probiotics against sepsis-related heart injury using a rat model caused by lipopolysaccharide (LPS). Materials and Methods: Four groups of twenty-four male Wistar albino rats, each with six rats, were set up. For 14 days, Group 1 (Sham Group) was given oral normal saline, intraperitoneal Escherichia coli O111-B4 lipopolysaccharide (LPS Group) was given to Group 2, and oral probiotics were given to Group 3 (Probiotic Group). Escherichia coli O111-B4 lipopolysaccharide was injected intraperitoneally after Group 4 (Probiotic + LPS) received oral probiotics containing Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 (109 CFU/day). Blood samples were taken twenty-four hours following the administration of LPS. The animals were then euthanized by cervical dislocation, and samples of cardiac tissue were taken in order to assess any damage to the heart. The following serum values were measured: C-reactive protein (CRP), creatine kinase-myocardial band (CK-MB), cardiac troponin subunit I (cTn-I), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The TNF-α, IL-1β, IL-6, glutathione (GSH), malondialdehyde (MDA), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), CRP, CK-MB, and cTn-I levels were assessed in tissue samples. Additionally, staining techniques were used to analyze histopathological alterations in tissues. Results: With the exception of serum IL-6 (p = 0.111), tissue and serum cytokine levels were considerably greater in the sepsis group (Group 2) than in the other groups (p < 0.05 to <0.001). The TAS, GSH, and SOD levels were significantly lower (p < 0.05 to <0.001) in septic rats, although the tissue levels of TOS, OSI, and MDA were significantly higher. With the exception of serum CRP in Group 3 (p = 0.328), the CK-MB, CRP, and cTn-I levels were considerably higher in Group 2 than in the other groups (p < 0.01 to <0.001). When compared to the other groups, histopathological examination showed significant alterations in the LPS group. Conclusions: Probiotics showed positive effects on oxidative stress markers and dramatically decreased sepsis-induced cardiac damage in the LPS-induced sepsis model. These results imply that probiotics could be used as a therapeutic approach to lessen the cardiac damage brought on by sepsis.

Gökçelik, Eda; Yılmaz, Coşkun; Budak, Cemallettin; Soylu, Hakan Hüseyin; Bayrakdaroğlu, Serdar; Ceylan, Halil İbrahim; Muntean, Raul Ioan; Küçük, Hamza; Ceylan, Levent

Background and Objectives: Post-menopausal estrogen decline is considered a contributing factor to sarcopenia, and inspiratory muscle training (IMT) may provide benefits in this demographic. This study examined the impact of a four-week IMT program on diaphragm thickness, abdominal wall muscle thickness (AWMT; transversus abdominis, internal oblique, and external oblique), and liver fat percentage in healthy elderly women. Materials and Methods: Twenty-six women aged 60–80 years were randomly assigned to an IMT group (n = 13) or a control group (n = 13). The IMT group used the PowerBreathe® Classic device at 40% of maximal inspiratory pressure (MIP), with weekly increments of 10%. Training was performed twice daily, five days per week, with 30 breathing cycles per session (60 per day). The control group maintained their usual routines. AWMT, diaphragm thickness (DT), and fatty liver density (FLD) were measured by a radiologist before and after the intervention. Results: After four weeks, the IMT group showed significant improvements in all parameters compared to controls. Mid-diaphragm thickness (MDT) increased by 11.44% (effect size (ES) = 0.358, p < 0.001) versus 0.76% in controls (p = 0.271). Posterior diaphragm thickness (PDT) improved by 7.48% (ES = 0.282, p < 0.001) versus 0.38% (p = 0.564). Right AWMT increased by 12.7% (ES = 0.492, p < 0.001) compared to 0.10% (p = 0.872), and left AWMT increased by 9.93% (ES = 0.395, p < 0.001) versus 2.64% (p = 0.014). FLD improved by 11.79% (ES = 0.959, p < 0.001) in the IMT group, while the control group showed no meaningful change (−0.13%, p = 0.847). Conclusions: A short-term IMT protocol significantly enhanced diaphragm and AWMT and reduced liver fat in elderly women. These findings support the use of IMT as a simple, non-invasive intervention to preserve musculoskeletal and metabolic health in aging populations.

Ergün, Sefa; Kutluk, Fadime; Turgut, Basar Can; Dumur, Seyma; Sayılı, Uğurcan; Ergun, Dilek Duzgun; Uzun, Hafize

Background and Objectives: Chronic mucosal infection with Helicobacter pylori (H. pylori) plays a key role in the development of gastroduodenal disorders such as chronic gastritis, peptic ulcers, gastric lymphoma, and gastric cancer by triggering local immune responses and inducing hypoxic and inflammatory conditions in the gastric mucosa. This study aims to evaluate the potential diagnostic value of hypoxia-inducible factors HIF-1α and HIF-2α, along with transmembrane prolyl 4-hydroxylase (P4H-TM), as biomarkers in H. pylori-positive patients. Additionally, the study investigates the association between these markers and alterations in lipid profiles, as well as their involvement in the molecular mechanisms underlying gastric conditions like gastritis, particularly in the context of H. pylori infection. Materials and Methods: This study was conducted at Istanbul Avcılar Murat Kölük State Hospital’s General Surgery Outpatient Clinic. A total of 60 participants were included: 40 patients diagnosed with chronic gastritis (20 H. pylori-positive and 20 H. pylori-negative) and 20 healthy controls confirmed negative by 13C-urea breath test. Blood samples were collected for ELISA analysis of HIF-1α, HIF-2α, and P4H-TM levels. Additionally, lipid profiles were measured and compared among the groups. Results: No significant differences were found among the groups in terms of demographic factors such as age, sex, or body mass index (BMI). However, significant variations were observed in the levels of HIF-1α, HIF-2α, and P4H-TM across all groups (p < 0.001 for each marker). These markers were substantially elevated in the H. pylori-positive gastritis group compared to both the H. pylori-negative and healthy control groups. Receiver Operating Characteristic (ROC) curve analysis revealed that all evaluated markers exhibited strong diagnostic accuracy in differentiating H. pylori-positive individuals from other groups. HIF-1α (AUC: 0.983) and HIF-2α (AUC: 0.981) both achieved 100% sensitivity with specificities of 93.3% and 91.1%, respectively. P4H-TM showed an AUC of 0.927, with 85% sensitivity and 95.6% specificity. Conclusions: These findings indicate that HIF-1α, HIF-2α, and P4H-TM may serve as effective biomarkers for diagnosing H. pylori-positive patients and may be linked to changes in lipid metabolism. The elevated expression of these markers in response to H. pylori infection highlights their potential roles in the inflammatory and hypoxic pathways that contribute to the pathogenesis of gastric diseases such as gastritis.

Barkay, Orçun; Karakeçili, Faruk

Background: Coronavirus Disease-2019 (COVID-19) has posed formidable challenges to healthcare systems. Exploring novel biomarkers that can provide valuable prognostic insights, particularly in critically ill patients, has a significant importance. Against this backdrop, our study aims to elucidate the associations between serum chloride levels and clinical outcomes. Methods: A total of 499 patients were enrolled into the study. The serum chloride levels of patients upon hospital admission were recorded and then categorized into three groups (hypochloremia, normochloremia, and hyperchloremia) for the evaluation of clinical outcomes. Additionally, serum C-reactive protein, procalcitonin, and D-dimer measurements were recorded for further evaluation. Results: A total of 390 (78.1%) patients tested positive for COVID-19 via polymerase chain reaction testing. Non-contrast thorax computed tomography scans were indicative of COVID-19 compatibility for all patients. A total of 210 (42%) patients were female and 289 (58%) were male. A total of 214 (42.8%) patients necessitated tocilizumab intervention; 250 (50.1%) were at an intensive care unit (ICU), with 166 (66.4%) of them receiving tocilizumab. A total of 65 (13%) patients died, 40 (61.5%) of whom received tocilizumab; 41 (63%) were in the ICU. Serum chloride levels upon admission were markedly lower and elevated D-dimer levels were apparent in tocilizumab users, patients requiring ICU care, and patients who died. Conclusions: our findings provide robust evidence supporting the value of serum chloride levels as a prognostic biomarker in critically ill COVID-19 patients.

Yilmaz, Mehmet; Suleyman, Bahadir; Mammadov, Renad; Altuner, Durdu; Bulut, Seval; Suleyman, Halis

Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.

Aydın, Hasan; Kızılgöz, Volkan; Ersan, Önder; Hekimoğlu, Baki

Background and objectives: Our aim is to determine the diagnostic performance and utility of Diffusion Weighted MR Imaging (DWI) against the routine Magnetic Resonance Imaging (MRI) for the evaluation of patients with tendon injuries of the ankle and foot. Materials and Method: After institutional review board approval and informed consent taken from all the patients, ankle and foot MR imaging and DWI-Apparent Diffusion Coefficient (ADC) mapping were performed on the 81 injured tendons of 50 patients. All tendon injuries were named as Rupture (R), Partial tear (PT), and Tenosynovitis (T). Diagnostic interpretation was based on the MRI-DWI and ADC mapping, verified by either open surgery, diagnostic arthroscopy, or conservative procedures-splint application. Statistical analysis of this research was assessed by Fischer’s exact test, variance analysis test between dependent groups, Receiver Operating Characteristics (ROC) curve, and Pearson chi square statistics. Results: MRI depicted all tendon injuries with 70% sensitivity and 100% specificity, and showed a significant statistical relationship to surgical and arthroscopic references with high agreement (p < 0.05, k: 0.609). DWI had 100% sensitivity and 83–90% specificity for the visualization of tendon injuries with certain agreement and a significant statistical relationship to the gold standard (p < 0.05, k: 0.890–0.899). For all those injured tendons, DWI had 100% sensitivity for the diagnosis of R, and 92–97% sensitivity corresponding to PT and T over routine ankle MR imaging. The specificity of DWI to MRI ranged from 75 to 44% for all the injured tendons. DWI had significant statistical superiority over MRI for the visualization of R, PT, and T of all tendons included in this research (p < 0.05). Conclusions: DWI is a good imaging modality for the visualization of ankles with tendon injuries, possibly further improving the sensitivity of the classical ankle and foot MRI, and supplying more beneficial and diagnostic information than routine MR imaging on the basis of R, PT, and T of tendons at the ankle and foot.

Karavaş, Erdal; Karakeçili, Faruk

Background and objectives: In this study, we compare portal vein Doppler ultrasound (US) findings between patients with Crimean–Congo hemorrhagic fever (CCHF) and healthy persons and investigate the practicability of these findings in the prediction of disease severity. Materials and Methods: In this prospective study, portal vein Doppler US was performed in patients diagnosed with CCHF and healthy persons between March 2016 and May 2018. The patients were grouped according to mild-to-moderate and severe progression of CCHF. Liver size, portal vein diameter, portal vein flow rate, spleen volume, and splenic vein diameter were recorded in the patients and healthy controls. Results: Of the 48 patients diagnosed with CCHF, 25 were male. According to the scoring made, 38 patients were evaluated as having mild-to-moderate disease progression, and 10 were evaluated as having severe disease progression. With respect to the Doppler US findings, liver size, spleen volume, portal vein diameter, splenic vein diameter, and portal vein flow rate were significantly higher in the patient group compared with the controls. However, no significant difference was found in these parameters between the severe and mild-to-moderate progression groups. Conclusions: In the evaluation of and follow-up with patients with CCHF, portal vein Doppler US is a non-invasive and reliable tool for diagnosis.