Acta Medica

Mismatch Repair (MMR) protein expression in liver tissue and cancer: A study utilizing Human Protein Atlas Data

Meral Üner — 2026-06-28

Objective: Alterations in mismatch repair (MMR) protein expression have been reported in liver cancers, including hepatocellular carcinoma and cholangiocarcinoma. Loss or reduced expression of MMR proteins is commonly associated with microsatellite instability (MSI), which has important prognostic and therapeutic implications. Immunohistochemistry represents a cost-effective and reliable method for detecting deficient MMR (dMMR). However, due to potential technical pitfalls and variable staining patterns, careful interpretation of MMR immunostaining is required.

Materials and Methods: In this study, virtual slides of tumor microarray cores from 35 patients were re-evaluated. The cases were stained with different antibody clones targeting MLH1, PMS2, MSH2, and MSH6. Based on the percentage of nuclear staining, immunohistochemical expression patterns were categorized as: (1) total expression loss (<25% nuclear staining), (2) focal expression loss (25-75% nuclear staining), and (3) intact expression (>75% nuclear staining).

Results: Among 35 cases (21 hepatocellular carcinomas and 14 cholangiocarcinomas), clone-dependent variability in MMR immunohistochemistry performance was observed. Using the most effective antibody clones, potential dMMR patterns in hepatocellular carcinoma were identified in 25% of cases for MLH1, 50% for MSH2, and 50% for MSH6. In contrast, no dMMR-like pattern was observed in cholangiocarcinoma for any MMR protein. PMS2 (single available clone, CAB010235) demonstrated minimal expression in normal liver tissue and variable staining in tumors, suggesting technical limitations rather than true biological loss. These findings indicate that suboptimal antibody clones may artificially increase the apparent dMMR rate.

Conclusion: This study evaluated MMR protein expression patterns in hepatocellular carcinoma and cholangiocarcinoma using data from the Human Protein Atlas, an open-access resource. Although immunohistochemistry remains a cost-effective and reliable method, factors such as fixation quality, antibody clone sensitivity, and careful evaluation of internal controls must be considered. Appropriate antibody clone selection is therefore essential for accurate interpretation of MMR immunostaining.

Survival analysis of trauma implants in orthopedic surgery

Melih Oral — 2026-06-28

Objective: This study aimed to evaluate the survivability and success rate of medical trauma implants used in orthopedic trauma surgery. Fracture union rates, postoperative complications, and implant failures were analyzed to determine the overall performance of the implants.

Materials and Methods: The study included 455 patients (621 fractures) who underwent surgical fixation with Oltho Medical orthopedic trauma implants at Hacettepe University between January 2020 and July 2022. Patients with at least six months of follow-up and adequate radiographic evaluation were included. Fracture healing was assessed using the Radiographic Union Scale for Tibia (RUST) and a similar four-cortex scoring system for other fractures. Implant failures, postoperative complications, and patient demographics were recorded.

Results: The mean patient age was 34.2 ± 24.3 years (range: 6–93), with a mean follow-up of 16 months. The overall fracture union rate was 97.2% at six months, with a mean RUST score of 10.5. The implant survival rate was 98.7%, with implant failure observed in six (1.3%) cases. Postoperative complications occurred in 7.3% of patients, including wound complications (6.2%), nonunion (1.3%), and implant failures (1.3%). Although implant-specific survival rates varied among anatomical regions, all fractures ultimately achieved union following appropriate management.

Conclusion: Medical trauma implants demonstrated high survivability and effectiveness in fracture fixation, with a low failure rate comparable to existing literature. Despite some complications, all were successfully managed, supporting the reliability of these implants in orthopedic trauma surgery.

Impact of age and solvent exposure on audiometric abnormalities among automotive production workers: A cross-sectional study from Türkiye

Fatma Bozdağ — 2026-06-28

Objectives: This study investigates the relationship between occupational noise, solvent exposure, and audiometric abnormalities in male automotive industry workers, focusing on factors associated with audiometric abnormalities, including age, body mass index, and biochemical markers.

Methods: This cross-sectional study was conducted among 500 male workers who were admitted to the outpatient clinic of Ankara Occupational and Environmental Diseases Hospital for periodic health examinations between September 1, 2020, and July 1, 2021. Audiometric results and biochemical markers, including hippuric acid, trichloroacetic acid, and manganese, were assessed alongside demographic and occupational variables. Multivariate logistic regression was used to identify predictive factors for abnormal audiometry results.

Results: Among the participants, 61.2 % exhibited abnormal audiometry results, and 11.4 % had noise-induced hearing loss. Age strongly predicted abnormal audiometry (OR = 1.11, 95% CI: 1.07–1.15, p < 0.001), with an 11% increase in odds per year. Elevated trichloroacetic acid (TCA) levels were also associated with a 9% increase in odds of abnormal audiometry (OR = 1.09, 95% CI: 1.01–1.18, p = 0.027). No significant associations were found for body mass index, duration of work, or hippuric acid levels.

Conclusions: Age and TCA levels were significantly associated with audiometric abnormalities among workers exposed to occupational noise and solvents. These findings highlight the need for targeted interventions, including regular audiometric evaluations and minimizing solvent exposure, to reduce the risk of hearing loss in industrial settings. Further research is needed to explore the underlying mechanisms linking solvent exposure and auditory dysfunction.

Cam-type femoro-acetabular impingement: Mid-term functional results and joint awareness of arthroscopic, mini-open and surgical dislocation techniques

Rıza Mert Çetik — 2026-06-28

Objective: To evaluate the mid-term results of three different surgical techniques utilized for the treatment of femoro-acetabular impingement, by means of functional outcomes and joint awareness.

Materials and Methods: 53 patients were selected retrospectively, treated by one of the three surgical techniques: hip arthroscopy (HA), anterolateral mini open (AMO) or surgical hip dislocation (SHD). Patients with <12 months of follow-up were excluded. Median follow-up period was 57.5 months (range 16-256 months). Primary outcome measures were the Forgotten Joint Score (FJS), Harris Hip Score (HHS) and UCLA activity index. Surgical success was determined as FJS≥70 and a regression analysis was performed on different radiological and clinical parameters for the risk of failure.

Results: Mean post-operative FJS was 74.5 (±13.8) for the HA group, 72.6 (±17) for the AMO group and 52.7 (±24) for the SHD group (p=0.023). Pre-operative and post-operative HHS and UCLA were similar. Post-operative alpha angles were similar (p=0.597). Regression analysis results showed two factors affecting surgical success: pre-operative Tönnis stage (adjusted OR±95% CI: 0.091±0.005-0.659 ; p=0.023) and type of surgery performed (HA: adjusted OR±95% CI: 11.2±1.2-50.5, p=0.029; for AMO: adjusted OR±95% CI: 7.2 ±1.1-48.8, p=0.041).

Conclusion: Despite allowing more complete assessment of the hip joint, SHD results in inferior outcomes when evaluated with FJS.Three surgical approaches provide similar radiological and functional results if evaluated with conventional outcome scores of HHS and UCLA.

Predictive value of the HALP score for lymph node metastasis in resectable gastric cancer

Yasin Orhan Erkuş — 2026-06-28

Objective: This study aimed to evaluate the predictive value of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score for lymph node metastasis (LNM) in patients with resectable gastric cancer and to investigate the relationship between hematological markers and LNM.

Materials and Methods: Patients who underwent surgery for gastric adenocarcinoma between 2020 and 2024 were retrospectively analyzed. Demographic data, comorbidities, and laboratory parameters were recorded, and the HALP score, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet-to-neutrophil ratio (PNR) were calculated. Tumor stage, nodal stage, and pathological features were reviewed. The optimal HALP cutoff value was determined by receiver operating characteristic (ROC) curve analysis. Variables significant in univariate analysis were included in multivariate logistic regression to identify independent risk factors for LNM.

Results: A total of 238 patients were included, with a mean age of 65.5 ± 11.4 years; 70.2% were male. The mean number of dissected lymph nodes was 26.0 ± 10.6, and the mean number of metastatic nodes was 6.2 ± 9.0. Perineural invasion (PNI) and lymphovascular invasion (LVI) were observed in 66.8% and 71.0% of patients, respectively. LNM was present in 159 patients (66.8%). In univariate analysis, a low HALP score, advanced invasion depth, and the presence of PNI and LVI were significantly associated with LNM (p < 0.005). ROC analysis identified an optimal HALP cutoff value of 17 (AUC = 0.581, p = 0.041). In multivariate analysis, invasion depth (p = 0.001), PNI (p = 0.008), and LVI (p < 0.001) were independent predictors of LNM, whereas the HALP score was not (p = 0.221).

Conclusion: In resectable gastric cancer, a low HALP score was associated with lymph node metastasis but was not confirmed as an independent predictive factor. As a composite parameter reflecting systemic inflammation and immune–nutritional status, the HALP score may indicate tumor aggressiveness and poor prognosis. Preoperative recognition of low HALP(<17) scores may help identify patients requiring closer monitoring for LNM risk.

The performance of ChatGPT and Google Bard in medical oncology board examination

Taha Koray Şahin — 2026-06-28

Objective: Artificial intelligence (AI) is transforming healthcare, and large language models (LLMs) like ChatGPT and Google Bard have shown promise in providing medical information and decision support. The LLMs performed similarly or better than human participants in several board exams. However, their proficiency in complex clinical scenarios, like in oncology board exams, remains unclear. We aimed to assess the performance of three LLMs (ChatGPT 3.5, ChatGPT 4 and Google Bard) on the oncology board examination.

Materials and Methods: We utilized a question bank from the Turkish Society of Medical Oncology Board Exam encompassing 290 multiple-choice questions from 2021-2023. ChatGPT 3.5, ChatGPT 4, and Google Bard were asked to answer each question in both Turkish and English, providing explanations and confidence levels with their answers.

Results: The overall accuracy of LLMs was 59.3%, 42.8%, 36.2% for ChatGPT4, ChatGPT3.5, and Google Bard, respectively. The accuracy of ChatGPT 4 was significantly higher than that of ChatGPT 3.5 (p<0.001) and Google Bard (p<0.001), while the accuracy of ChatGPT3.5 was higher than that of Google Bard (p<0.001). Only the ChatGPT 4 was proficient in all three examination years (2021-2023). All LLMs performed better on translated questions than original Turkish ones. The LLMs were more accurate in general knowledge than case questions and were more confident in their answers for translated questions.

Conclusion: LLMs had moderate success in a medical oncology board exam, with only ChatGPT 4 demonstrating proficiency. The efficacy of LLMs in clinical decision-making requires further development, especially in native languages and complex case interpretations.

Diagnostic challenges in suspected mitochondrial disease: Clinical, metabolic, and genetic findings

Doina Secu — 2026-06-28

Objectives: This study delineates the diagnostic architecture of patients referred with suspected mitochondrial disease through the integrated analysis of clinical, biochemical, instrumental, and genetic data. By comparing patients with mitochondrial involvement, alternative genetic disorders, and unresolved cases, we aim to define phenotypic and molecular patterns associated with diagnostic stratification and characterize the diverse spectrum of genetic and non-genetic conditions that converge phenotypically on mitochondrial disease.

Materials and Methods: A total of 240 patients with clinical suspicion of mitochondrial disease were consecutively enrolled and assessed using a modified Nijmegen Mitochondrial Disease Score. All participants underwent comprehensive clinical, metabolic, instrumental, and neuroimaging evaluations, complemented by systematic molecular analyses, starting with common mitochondrial variant screening and progressing to more extensive targeted investigations guided by clinical and biochemical findings. Comparative analyses across the three groups employed nonparametric and categorical statistical tests.

Results: Relevant molecular findings were identified in 81 patients (33.7%), encompassing 37 (15.4%) with mitochondrial involvement and 44 (18.3%) with alternative genetic disorders, while 159 individuals (66.3%) remained unresolved. The mitochondrial group exhibited significantly higher rates of neuromuscular, brainstem, ophthalmic, and cardiac involvement, along with developmental regression, whereas seizures were a shared hallmark of both mitochondrial and non-mitochondrial subgroups. Biochemically, elevated serum lactate and plasma alanine were the most discriminative markers for the mitochondrial group, with a significantly higher prevalence of abnormal acylcarnitine profiles and organic aciduria in both the mitochondrial and alternative genetic subgroups. The undiagnosed cohort demonstrated phenotypic convergence with confirmed cases but lacked definitive molecular correlates despite extensive evaluation.

Conclusions: These findings underscore the intrinsic complexity and phenotypic heterogeneity of suspected mitochondrial disease, affirming the critical role of integrated clinical, metabolic, instrumental, and molecular assessment while simultaneously highlighting the limitations of current diagnostic paradigms and the imperative for expanded genomic and functional strategies to enhance resolution in unresolved cases.

Comparative prognostic performance of ELN 2022 and ELN 2024 risk classifications in a Turkish cohort of acute myeloid leukemia patients receiving hypomethylating agents and BCL-2 inhibitors

Selin Küçükyurt Kaya — 2026-06-28

Objective: The European LeukemiaNet (ELN) 2022 risk classification for acute myeloid leukemia (AML) was primarily developed in cohorts treated with intensive chemotherapy and has demonstrated limited prognostic discrimination in AML patients receiving less-intensive regimens. The recently proposed ELN 2024 classification aims to refine risk stratification in patients treated with less-intensive regimens. We compared the prognostic performance of ELN 2022 and ELN 2024 in a real-world cohort of unfit AML patients treated with azacitidine plus venetoclax.

Materials and Methods: In this retrospective single-center study, 39 newly diagnosed AML patients treated with first-line azacitidine and venetoclax between January 2023 and September 2025 were included. Patients were stratified according to ELN 2022 and ELN 2024 criteria. Overall survival (OS) was analyzed using Kaplan–Meier estimates, log-rank tests, Cox regression, and Harrell’s concordance index (C-index).

Results: Median age was 70 years (range, 60–84). Secondary AML was present in 33.3%, and 30.8% harbored TP53 mutations. Under ELN 2022, 64.1% of patients were classified as adverse risk compared with 30.8% under ELN 2024. ELN 2022 did not significantly stratify OS in either three-group or dichotomized analyses (p=0.265 and p=0.199, respectively). In contrast, dichotomized ELN 2024 demonstrated significant survival separation (p=0.041). Adverse risk according to ELN 2024 was associated with inferior OS (HR 2.41, 95% CI 0.98–5.94; p=0.057). The highest discriminatory capacity was observed with the dichotomized ELN 2024 model (C-index 0.697; p=0.021).

Conclusion: In AML patients treated with hypomethylating agents plus venetoclax, ELN 2024 provides improved prognostic discrimination compared with ELN 2022. These findings support the clinical relevance of treatment-context–specific risk stratification in the venetoclax era.

Biased and inadequate, or trustworthy and sufficient? Evaluating the YouTube videos on platelet-rich plasma in orthopedics

Gökhan Ayık — 2026-06-28

Objective: Social media has transformed patient-physician interactions, with YouTube emerging as a major contributor. Platelet-rich plasma (PRP) therapy has gained substantial popularity in orthopedics despite ongoing debate regarding its effectiveness. As orthobiologic treatments are increasingly promoted directly to consumers, concerns have emerged regarding the quality, reliability, and potential bias of online information. This study aimed to evaluate the quality, reliability, and bias of YouTube videos related to PRP in orthopedics.

Materials and Methods: A cross-sectional analysis of YouTube was performed, using the search terms “prp,” “prp knee,” and “prp shoulder.” The first 50 results were recorded, and after exclusions, eligible videos were analyzed. Video metadata were recorded and content sources were categorized as physician, medical institution, or non-medical sources. Information quality was assessed using Brief DISCERN instrument, JAMA Criteria, and Global Quality Score (GQS). Bias was evaluated based on predefined criteria including promotional language and testimonial-driven claims.

Results: A total of 111 videos were analyzed. Physicians produced 49.5% of videos, followed by institutions (39.6%) and non-medical sources (10.8%). Overall information quality was low-to-moderate, with median Brief DISCERN, JAMA, and GQS scores of 17, 3, and 3, respectively. Significant differences were observed between uploader types for all quality metrics (DISCERN p=0.008; JAMA and GQS p<0.001). Physicians demonstrated higher quality compared to medical institutions and non-medical sources. Overall, 40.5% of videos were classified as biased, with no significant association between source and bias (p=0.0516). Non-biased videos had higher JAMA (p=0.038) and GQS (p=0.025) scores. Longer videos were associated with higher quality and engagement (all p<0.001), while popularity metrics were not associated with information quality.

Conclusion: YouTube videos on PRP in orthopedics demonstrate variable quality, incomplete transparency, and a notable proportion of potentially biased content. Physician-generated content is associated with higher quality, although overall reliability and transparency remain inconsistent. These findings highlight both the need and the opportunity for more accurate, transparent, balanced, and evidence-based content to better support patient decision-making.

Is primary hyperparathyroidism associated with less aggressive histological subtypes and clinicopathological features of papillary thyroid carcinoma? A large single-center cohort study

İbrahim Kılınç — 2026-06-28

Objective: The coexistence of primary hyperparathyroidism (PHPT) and papillary thyroid carci-noma (PTC) has been increasingly recognized; however, its impact on tumor behavior and clinicopathological features remains unclear. To investigate the association be-tween PHPT and the clinicopathological characteristics of PTC in a large single-center cohort.

Materials and Methods: This retrospective study included patients who underwent parathyroidectomy for PHPT between 2019 and 2024. Patients with concomitant PTC were identified and compared with a separate cohort of patients with PTC without PHPT. Demographic, biochemical, and clinicopathological features, including tumor subtypes and adverse pathological characteristics, were analyzed.

Results: Among 190 patients with PTC, 91 (47.9%) had concomitant PHPT. Patients with PHPT were older and more frequently female. Tumor size was significantly smaller in patients with PHPT. Aggressive histological subtypes were significantly less frequent in the PHPT group (8.8% vs. 21.2%, p = 0.017). In addition, capsular invasion, lym-phovascular invasion, perineural invasion, and lymph node metastasis were observed less frequently in patients with PHPT. Radioactive iodine use was also significantly lower in this group.

In the PHPT cohort (n = 750), the presence of concomitant PTC was not associated with significant differences in preoperative calcium, phosphorus, PTH, or ALP levels. However, patients with PTC had lower preoperative magnesium levels and exhibited distinct postoperative biochemical profiles.

Conclusion: PHPT may be associated with non-aggressive subtypes and more favorable clinico-pathological features in PTC. However, these findings should be interpreted cautious-ly, as tumor size and other potential confounders may influence the observed associa-tions. PHPT alone should not be considered a determinant for treatment de-escalation, and clinical decision-making should remain guided by established risk-adapted strategies. These findings may provide additional insight into risk stratification in patients with coexisting PHPT and PTC.

Rethinking unresponsiveness: Cognitive motor dissociation in disorders of consciousness

Okan Sökmen — 2026-06-28