Tıp Fakültesi Koleksiyonu
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Article Alkaptonuria as a Cause of Pseudo-Proteinuria in Two Children Evaluated for Renal Disease(Springer, 2026-03-23) Becerir, Tulay; Kilic, Pinar; Girisgen, Ilknur; Altintas, Ummuhan Seda; Kabukcuoglu, Mirac Burak; Yuksel, SelcukProteinuria in childhood is a major warning sign of kidney disease and often prompts an extensive diagnostic work-up. However, not all protein detected by routine laboratory methods reflects true renal protein loss, and analytical interference may lead to misinterpretation and unnecessary invasive procedures. Alkaptonuria is a rare autosomal recessive disorder of tyrosine metabolism characterized by lifelong accumulation of homogentisic acid, which is known to interfere with some colorimetric urine protein assays and may cause pseudo-proteinuria. We report two children evaluated in a pediatric nephrology setting because of significant proteinuria. The first patient, who had familial Mediterranean fever, underwent kidney biopsy to exclude amyloidosis before the diagnosis of alkaptonuria was considered after a seemingly minor historical clue provided by the mother. The second patient was followed after a severe episode of hemolytic uremic syndrome, and persistent proteinuria was initially attributed to residual renal damage; however, further evaluation revealed underlying alkaptonuria and a marked discordance between total protein and albumin excretion. These cases illustrate an important diagnostic pitfall and emphasize that, particularly in the presence of discordance between total urine protein and albumin, pseudo-proteinuria should be considered. A simple question such as whether the urine darkens on standing may provide a crucial clue and prevent unnecessary investigations.Conference Object Malignant Solid Pseudopapillary Neoplasms: Histological Features, Molecular Alterations and Survival Outcomes(Springer, 2025) Comut, E.; Celik, A.; Uguz, A.; Ergun, O.; Erbil, S.; Argon, A.; Nart, D; Demirkan, N. Calli; Yilmaz, F.Article Understanding Antipsychotic Polypharmacy in Bipolar Disorder: The Role of Long-Acting Injectable Antipsychotics in a Naturalistic Inpatient Setting(Springer, 2026-01-10) Oktar Erdogan, Nilgun; Yucens, Bengu; Ozcan, Osman Mert; Ayhan, Fatmanur; Tumkaya, SelimAntipsychotic (AP) polypharmacy is common in the treatment of bipolar disorder (BD), particularly during inpatient care. Long-acting injectable antipsychotics (LAIs) are frequently used to prevent relapse. However, their relationship with AP polypharmacy remains unclear. This study examined the prescription patterns in inpatients with BD, focusing on the relationship between clinical characteristics, LAI use, and AP polypharmacy. Sociodemographic and clinical data of 175 inpatients diagnosed with BD were retrospectively analyzed. Antipsychotic use at three time points (pre-hospitalization, at initial treatment, and at discharge) was recorded. Factors predicting discharge AP count, AP dosage, and the potential direct and indirect effects of pre-hospitalization LAI use were examined. Patients using LAIs before hospitalization had earlier onset of illness, more manic episodes, and higher AP burden compared to non-users. Discharge AP count and dosage were significantly associated with AP count at initial treatment, length of hospital stay, and manic episode frequency. LAI use demonstrated a trend-level indirect association with fewer APs at discharge, mediated by shorter hospital stays, and this pathway appeared stronger among patients with fewer prior manic episodes. AP polypharmacy is common in BD, especially among patients on LAI. However, the association is indirect and shaped by clinical factors. Regular review of treatment regimens may help minimize unnecessary polypharmacy.Article Relationship of Cardiac MRI-Derived Pulmonary Arterial Stiffness Markers and Invasive Hemodynamic(Springer, 2026-01-03) Buber, Ipek; Heerdt, Paul; Singh, Inderjit; Phillip, Joseph; Sevgican, Cihan Ilyas; Lamy, Jerome; Xiang, Jie; Peters, Dana C.Pulmonary arterial stiffness (PAS) is a noninvasive imaging biomarker associated with disease severity in pulmonary hypertension (PH). This study aimed to evaluate PAS using cardiac magnetic resonance (CMR) imaging and investigate its relationship with hemodynamic parameters from right heart catheterization (RHC) across PH subgroups. In this retrospective study, 44 patients with PH who underwent both RHC and CMR were classified into pre-capillary (precapPH), post-capillary (postcapPH), and combined pre- and post-capillary (combPH) PH groups based on guideline-defined criteria. PAS was assessed by CMR-derived pulse wave velocity (PWV) and relative area change (RAC) of the main pulmonary artery. RHC measurements included mPAP, PVR, and right ventricular pressures and mixed venous saturation. PWV was significantly higher in combPH (4.49 +/- 1.32 m/s) compared to precapPH (3.40 +/- 0.98 m/s, p = 0.04). RAC was significantly lower in combPH (0.18 +/- 0.11) than in postcapPH (0.28 +/- 0.09), p = 0.01) and precapPH (0.18 +/- 0.07, p = 0.01). PWV correlated with mPAP (r = 0.34, p = 0.022), RAP (r = 0.39, p = 0.008), and RVEDVi (r = 0.34, p = 0.022), while RAC showed a negative correlation with PVR (r = - 0.36, p = 0.01). Distinct RV adaptation patterns were observed among subgroups, with combPH patients exhibiting the most impaired hemodynamics. CMR-derived PAS indices correlate with invasive hemodynamic markers and differ among PH subtypes. PWV and RAC may serve as useful noninvasive markers for assessing pulmonary vascular burden and differentiating disease severity in PH. Larger prospective studies are needed to validate their clinical utility.Article Bevacizumab Combined With Irinotecan or Temozolomide in Recurrent Glioblastoma: A Turkish Oncology Group (TOG) Study(Springer, 2026-01) Akbas, Sinem; Alan, Ozkan; Yildiz, Oguzhan; Karakurt, Melek; Yildirim, Eda Caliskan; Colak, Rumeysa; Yilmaz, Mesut; Selcukbiricik, FatihPurpose Given the lack of an effective systemic therapy for recurrent glioblastoma, this study aims to compare response rates, progression-free survival, overall survival, and toxicity profiles of bevacizumab in combination with temozolomide (TMZ) versus irinotecan. Methods We retrospectively analyzed patients with recurrent glioblastoma from seventeen oncology centers in Turkiye who received bevacizumab combined with either TMZ or irinotecan after progression. Outcomes included response rates, progression-free survival (PFS), overall survival (OS), and adverse events assessed by CTCAE v4.0. Results Among 210 patients with recurrent glioblastoma, the median PFS was 7.9 months overall (5.2 months with TMZ-bevacizumab and 8.2 months with irinotecan-bevacizumab), and the median OS was 10.6 months overall (11.3 and 10.3 months, respectively). Six-month PFS and OS rates were 60% and 68% for the entire cohort, with no statistically significant differences between treatment regimens. Both combinations were generally well tolerated, with hypertension more frequent in the TMZ arm and liver enzyme elevation more common in the irinotecan arm. Conclusion In this multicenter cohort of patients with recurrent glioblastoma, bevacizumab combined with either temozolomide or irinotecan demonstrated comparable PFS and OS outcomes. Both regimens were generally well tolerated, suggesting that treatment choice may be guided by individual patient profiles and toxicity considerations rather than differences in efficacy.Article Predictors of Intercultural Sensitivity in Medical Students: An Assessment in a Turkish University in an Era of Global Healthcare(Springer, 2025-11-10) Yalcin, Sibel Oner; Uzun, Suleyman UtkuIn an increasingly globalized world, intercultural sensitivity (ICS) has become essential for medical professionals. Turkiye's unique position as a bridge between continents and its growing international student population make understanding intercultural sensitivity among medical students particularly relevant. This study aimed to assess intercultural sensitivity levels among medical students and identify associated factors. A cross-sectional study was conducted among 412 medical students at Pamukkale University Faculty of Medicine during 2020-2021. Stratified random sampling ensured representation across all six academic years. Data were collected using a sociodemographic questionnaire, cultural interaction assessment, and the validated Turkish version of the Intercultural Sensitivity Scale (ISS). Bivariate analyses (t-tests, ANOVA) and multiple linear regression (backward elimination) identified independent predictors of total ISS scores. The overall mean ISS score was 93.02 +/- 10.80, indicating moderate-to-high ICS. Students scored highest on "Responsibility in Communication" and "Respect for Cultural Differences". Multiple regression analysis revealed five significant predictors: having international friendships (beta = 0.25, p < 0.001), frequent international media consumption (beta = 0.15, p = 0.004), higher foreign language proficiency (beta = 0.12, p = 0.026), absence of language barriers in cross-cultural interactions (beta = 0.18, p = 0.002), and absence of religion-related difficulties (beta = 0.13, p = 0.010). Medical students demonstrated moderate intercultural sensitivity, primarily influenced by direct cross-cultural experiences. These findings underscore the importance of fostering international interactions within medical curricula to enhance intercultural sensitivity.Article Real-World Comparison of Doxorubicin-Ifosfamide Versus Gemcitabine-Docetaxel Regimens in Metastatic Uterine Leiomyosarcoma: A Multicenter Retrospective Study(Springer, 2025-11-17) Tunbekici, Salih; Sahin, Gokhan; Yuksel, Haydar Cagatay; Acar, Caner; Akin, Imge; Aslanhan, Hasan; Isci, Mert; Goker, ErdemBackgroundUterine leiomyosarcoma is a rare and aggressive malignancy with limited responsiveness to standard therapies. We conducted a real-world, multicenter study to compare the clinical efficacy and safety of two commonly used first-line chemotherapy regimens-doxorubicin-ifosfamide and gemcitabine-docetaxel-in patients with metastatic uterine leiomyosarcoma.MethodsThis retrospective cohort included 271 patients with advanced or metastatic uterine leiomyosarcoma treated between 2010 and 2023 across 30 centers in Turkey. Patients received either doxorubicin-ifosfamide (n = 142) or gemcitabine-docetaxel (n = 129) as first-line therapy. The primary endpoint was overall survival; secondary endpoints included progression-free survival, objective response rate, disease control rate, and safety. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0, while survival outcomes were estimated using the Kaplan-Meier method and further analyzed with Cox proportional hazards models.ResultsMedian overall survival was 19.7 months with doxorubicin-ifosfamide and 20.2 months with gemcitabine-docetaxel (P = .26). Median progression-free survival was 5.5 months with doxorubicin-ifosfamide and 7.0 months with gemcitabine-docetaxel (P = .62). The objective response rate was numerically higher with gemcitabine-docetaxel (35% vs. 26%), although not statistically significant (P = .11). Grade 3-4 neutropenia (16% vs. 12%) and febrile neutropenia (7% vs. 6%) were more frequent with doxorubicin-ifosfamide.ConclusionsIn this largest-to-date real-world cohort of metastatic uterine leiomyosarcoma, doxorubicin-ifosfamide and gemcitabine-docetaxel demonstrated comparable survival outcomes. Gemcitabine-docetaxel, however, was associated with a more favorable hematologic safety profile. These findings support the clinical utility of both regimens while underscoring the need for prospective, biomarker-driven studies to refine treatment selection and improve personalization in this rare malignancy.Article Possible TLR-Mediated Immunostimulatory Effect of Palbociclib in Breast Cancer(Springer, 2025-11-26) Bayav, Ibrahim; Sag, Sevda; Ergezgin, Huriye; Dodurga, Yavuz; Tomatir, Ayse GayeBackgroundPalbociclib, which exerts its effect by inhibiting the cell cycle in cancer cells, is a CDK inhibitor used in the treatment of ER+/HER- breast cancer. In this study, we aimed to investigate the effect of Pablosiklib on TLR, which plays an important role in the immune response, in MCF-7 (ER+/HER2-) and MDA-MB-231 (ER-/PR-/HER2-) cell lines.Methods and resultsThe expression levels of TLR 1-10 genes, cell cycle-related genes (CDK4/6), and genes involved in the apoptotic pathway (Bcl-2, Bax, Cas-3) in MCF-7 and MDA-MB-231 cells treated with palbociclib were evaluated using the real-time PCR (qRT-PCR) method. Additionally, the levels of total retinoblastoma (RB) and phosphorylated retinoblastoma (pRB) proteins were analyzed using the Western blot method. CDK4/6 and pRB expression decreased in MCF-7 and MDA-MB-231 cells treated with palbociclib. Bax and Cas-3 expression increased, while Bcl-2 expression decreased. Changes in TLR expression were also observed.ConclusionsWe believe that palbociclib not only stops the cell cycle and induces apoptosis in breast cancer cells, but also activates the immune response via TLRs.Article Nutritional Status and Surgical Outcomes in Patients With Esophageal Atresia: Findings from Turkish Esophageal Atresia Registry(Springer, 2025-10-04) Soyer, Tutku; Bostanci, Suleyman Arif; Durakbasa, Cigdem Ulukaya; Ozcan, Coskun; Ciftci, Ilhan; Gollu, Gulnur; Parlak, Ayse; Dağ, OsmanPurpose To evaluate the relationship between nutritional status and surgical outcomes in patients with esophageal atresia (EA) from the Turkish Esophageal Atresia Registry (TEAR). Methods Between 2015 and 2024, 713 patients with the complete data of neonatal period and first year of life were included. According to FENTON, growth charts and patients were grouped as small for gestational age (SGA, < 10 percentiles), medium SGA (percentiles = 10-20), appropriate for gestational age (AGA, percentiles = 20-90) and large for gestational age (LGA, percentiles > 90) at birth. The z scores for height-for-weight were reevaluated at 6th and 12th months of age. Results Among 713 patients, 56% were boys. 23.7% of patients were SGA. There was no difference among groups for demographic features, outcomes, and mortality (p > 0.05). Patients with SGA had a higher rate of karyotype anomalies (23.1%, p < 0.05). At the 6th month, 20% of patients had improved nutritional status, 46.2% unchanged, and 33.5% worsened. At the 12th month, it was 31.6%, 50.2%, and 18.3%, respectively. 32.8% of the SGA patients had severe malnutrition at the 6th month, while this rate decreased to 10.2% at the end of the first year of life. Patients with worsened nutritional status had a significantly higher rate of mortality (10.2%) than patients with unchanged and improved nutritional status (3.7%, 2%, respectively, p < 0.05). There was no statistical difference between nutritional status and surgical outcomes at the 6th and 12th months (p > 0.05). Conclusions The incidence of SGA was significantly higher in EA patients with karyotype anomalies. While 20% of patients improved nutritional status at the 6th month, only one-third of patients improved nutritional status at the end of the first year. Closer follow-up is needed in patients with EA to avoid malnutrition, which can lead to poor growth, developmental delay, and impaired immune function.Article Investıgatıon of NTRK Fusıon in Non-Small Cell Lung Cancers by Immunohıstochemıcal and Molecular Methods(Springer, 2025-07-05) Ozturk, Ubeydullah; Kilicarslan, Emel; Taskoylu, Burcu Yapar; Oncel, Sevin Baser; Bir, FerdaNeurotrophic tyrosine receptor kinase (NTRK) fusions, which have been identified as a major genetic alteration in some tumors, have rarely been reported in more common tumors such as non-small cell lung carcinoma(NSCLC). In addition to immunohistochemical methods for NTRK fusion detection, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction and next generation sequencing tests are used molecularly. The aim of this study was to investigate to what extent NTRK gene fusion play a role in the tumorigenesis of NSCLC, associated with clinicopathologic parameters and prognosis. This retrospective study included 340 cases of NSCLC diagnosed in our institution. All cases were analyzed in terms of Pan-TRK immunohistochemical expression, clinicopathologic parameters and prognosis. Immunohistochemical Pan-TRK positivity was confirmed by reverse transcriptase-polymerase chain reaction. In cases in which NTRK fusion was detected by reverse transcriptase polymerase chain reaction, NTRK fusion was reconfirmed by fluorescence in situ hybridization. Immunohistochemical Pan-TRK (clone EPR17341) expression was observed in 25 (7.4%) cases. NTRK3 fusion was detected in 3 of these cases by reverse transcriptase-polymerase chain reaction test and confirmed by fluorescence in situ hybridization. Two NTRK fusion positive cases were squamous cell carcinoma and one case was adenocarcinoma. Our findings suggest that immunohistochemistry can be used as a screening test, but requires molecular confirmation. Our finding of NTRK3 fusion in squamous cell carcinomas with limited treatment options, suggests that the driver function of this gene may be more effective in this group.