Evaluation of New Generation Sequencing (NGS)-Based Somatic Gene Variations and Real-Time Polymerase Chain Reaction (PCR)-Based Gene Fusions in Elderly and Young Acute Leukemia Patients: A Retrospective View.

Malignant diseases occurring in elderly patients follow a different course from younger patients and show different genetic structures. Therefore, in this retrospective study, the somatic gene variant profile and fusion gene profiles of elderly and young acute leukemia patients were determined to draw attention to the existing genetic difference, and the results were compared. In this study, the records of 204 acute leukemia patients aged 18+ who were referred to the Molecular Pathology Laboratory from the Hematology Clinic between 2018 and 2022 were reviewed retrospectively. Fusion gene detection in patients was performed with the HemaVision®-28Q Panel. The NGS Myeloid Neoplasms Panel was conducted using the MiniSEQ NGS platform according to the manufacturer's protocol. When all cases are evaluated together, the most frequently diagnosed acute leukemia is acute myeloid leukemia (85.8%). Both groups had a similar fusion gene profile; however, the fusion burden was higher in the elderly group. When the groups were evaluated in terms of somatic gene variations, there were differences between the groups, and the variation load was higher in the elderly group. Considering the different somatic gene variation profiles, it is understood that the genetic structure of tumor cells is different in elderly patients compared to young cases.

Geriatric Importance of Histopathological Parameters Evaluated in Thyroidectomy Specimens: A Single Center Retrospective Analysis.

Nowadays, the aging human population exerts a notable influence on the treatment of thyroid diseases. The most appropriate approach for the treatment of benign and malignant thyroid diseases in older adults has not yet been determined. The aim of our study is to evaluate the effect of thyroidectomies in geriatric patients considering age, sex and histopathological parameters and to determine the importance of thyroidectomy as a treatment option in the geriatric population. A total of 910 cases from all age groups were included, for which thyroidectomies were examined and reported. In accordance with the College of American Pathologists Cancer Protocol for thyroid reporting, considering geriatric patients, the rate of Thyroid Follicular Nodular Disease was significantly higher among the tumor types in the benign tumor group (p = 0.033), while Anaplastic Thyroid Carcinoma rate was higher in the malignant tumor group. The diagnosis rate of malignant tumors was higher in males, reflecting a more advanced pT stage (p < 0.001), larger tumor size (p < 0.001) and increased lymph node involvement rate (p = 0.039). Given that increasing age is associated with a heightened incidence of thyroid disease, the safety of surgery for geriatric patients is an important issue. Thyroidectomy should be considered in the treatment of these patients, especially in males, as the rate of malignant diagnosis and worse histopathological parameters are seen with increasing age.

Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation.

BACKGROUND/AIMS: Recent studies that reveal the molecular profiles of colorectal carcinomas have demonstrated tumor heterogeneity. Characterization of colorectal carcinoma-specific genomic alterations is essential for developing more successful and targeted treat- ment protocols. Moreover, it is vital in elucidating the pathogenesis and mechanisms of resistance against treatment and predicting prognosis. MATERIALS AND METHODS: The study included 73 cases diagnosed with colorectal carcinomas and subjected to molecular analysis by the next-generation sequencing. The association between the clinicopathologic parameters and pathogenic mutations detected in 32 genes was evaluated. RESULTS: Pathogenic mutations were determined in a total of 24 genes. The Cell Division Cycle 27 (CDC27), Kirsten rat sarcoma viral proto-oncogene (KRAS), serine/threonine protein kinase B-raf (BRAF), phosphatase and tensin homolog, breast cancer 2 (BRCA2), and phosphotidylinositol-4,5-biphosphate 3-kinase (PIK3CA) mutations were determined at higher rates, with the adenomatous polypo- sis coli mutation determined at a lower rate than in the literature. There were significant positive correlations between CDC27 and phosphatase and tensin homolog (PTEN), PTEN and BRCA2, and PTEN and adenomatous polyposis coli (APC) concomitant muta- tions, whereas negative correlations were present between BRAF and KRAS. Statistically significant relationships were present between KRAS exon 2 and mucinous morphology, PIK3CA and absence of perineural invasion, BRAF and tumor differentiation/localization, MutS homolog 3 (MSH3) and tumor diameter, and BRCA2 and absence of lymph node metastasis. CONCLUSION: It is necessary to have a comprehensive database of genomic alterations of colorectal carcinomas to interpret mutations more accurately clinically. There are no studies on the frequency of mutations in colorectal carcinomas in the Turkish population; thus, follow-up and treatment protocols are organized following the European and American databases and guidelines. A comprehensive study of the colorectal carcinoma patients' mutation profile in the Turkish patient cohort by the next-generation sequencing method will help to provide significant therapeutic, prognostic, and predictive data and design more successful treatment and follow-up strategies.

Occupational Silica Exposure as a Potential Risk for Microscopic Polyangiitis.

Microscopic polyangiitis is an important and common component of cytoplasmic antibody-associated vasculitides that can lead to serious morbidity and even death. A clear causative etiology has not been identified. Although silica is well known to produce lung damage, the negative renal effects of silica exposure should not be overlooked. We present a case of renal dysfunction associated with silica exposure, its diagnosis by renal biopsy, and the treatment method used. Environmental or occupational silica exposure can cause microscopic polyangiitis. Working in occupations with increased risk of silica exposure may result in serious medical problems.

Evaluation of the Mutation Profile via Next-Generation Sequencing in a Turkish Population With Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer is the most common cancer type worldwide, with non-small cell lung cancer being the most frequently studied. Identifying of cancer-related genes in non-small cell lung cancer is crucial for developing individualized treatment, particularly as mutation profiles can vary by country and ethnicity. AIMS: To identify comprehensive mutation profiles in a cohort of Turkish patients with non-small cell lung cancer using the next-generation sequencing. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In total, 72 cancer-related genes and 4149 variants were recorded in the non-small cell lung cancer panel, and their relationship with clinical and histopathological features was investigated through next-generation sequencing. RESULTS: Among 507 patients, 420 (82.8%) were males and 87 (17.2%) were females. Percentages of phosp hatid ylino sitol -4,5- bisph ospha te 3-kinase catalytic subunit alpha (11%), B-Raf proto-oncogene, serine/threonine kinase (8%), and neurofibromatosis type 1 (6%) mutations were higher than those reported in the literature. Males had a higher rate of Kirsten rat sarcoma 2 viral oncogene homolog mutations (P = .102), whereas epidermal growth factor receptor mutations were statistically more common in females (P = .001). Multiple variants of strong significance were identified in 6.3% patients diagnosed with adenocarcinoma, most of whom were smokers. Kirsten rat sarcoma 2 viral oncogene homolog and phosp hatid ylino sitol -4,5- bisph ospha te 3-kinase catalytic subunit alpha mutations were most commonly observed. CONCLUSION: This study shows that Turkish patients have higher rates of PIK3CA, BRAF and NF1 mutations compared to the literature. Studies to determine the molecular profile specific to Turkish people will guide clinicians in treatment and contribute significantly to determining priorities in diagnosis.

Borate reduces experimental supra-celiac aortic clamping-induced oxidative stress in lung and kidney, but fails to prevent organ damage.

BACKGROUND: This study aims to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB) on aortic clamping-induced lung and kidney tissue oxidation, tissue inflammation, and histological damage in a rat model. METHODS: A total of 28 adult female Wistar albino rats were randomly allocated to four equal groups: Control group, ischemia-reperfusion group, dimethyl sulfoxide group, and 2-APB group. Animals in the control group underwent median laparotomy. In the remaining groups, supra-celiac aorta was clamped for 45 min and, then, reperfusion was constituted for 60 min. The 2-APB (2 mg/kg) was administered before clamping. The remaining groups received saline (ischemia-reperfusion group) or dimethyl sulfoxide (dimethyl sulfoxide group). Kidney and lung tissue samples were harvested at the end of reperfusion. RESULTS: Aortic occlusion caused increased tissue total oxidant status and reduced total antioxidant status and glutathione levels in the ischemia-reperfusion and dimethyl sulfoxide groups. Tissue interleukin-1 beta and tumor necrosis factor-alpha levels, nuclear factor kappa beta activation, and histological damage severity scores were also higher in these groups. The 2-APB treatment eliminated the increase in total oxidant status and the decrease in total antioxidant status and glutathione levels. It also caused a decrease in the interleukin-1 beta levels, although it did not significantly alter the tumor necrosis factor-alpha levels, nuclear factor kappa beta immunoreactivity, and histological damage scores. CONCLUSION: Borate exerted a beneficial antioxidant effect as evidenced by reduced oxidative stress; however, it did not inhibit nuclear factor kappa beta activation and prevent histological damage in supra-celiac aortic clamping-induced kidney and lung injury in rats.

Ozone Partially Decreases Axonal and Myelin Damage in an Experimental Sciatic Nerve Injury Model.

AIM: To investigate the effects of ozone in experimental acute sciatic nerve injury. MATERIAL AND METHODS: Twenty-eight male rats were divided into four groups (n = 7): control (C), ozone (O), injury (SNI), and treatment with ozone after injury (SNI + Ozone). Sciatic nerve injury was generated by compressing the right sciatic nerve for 90 s using a Yasargil aneurysm clip in groups SNI and SNI + Ozone. A 70 µg/ml concentration of ozone was given four times (once a day at 1st, 24th, 48th, and 72th h) at a dose of 0.5 mg/kg to groups O and SNI + Ozone after injury by an intraperitoneal injection. Nerve conduction velocities of all rats were measured by in vivo electrophysiological tests at the end of the day 4. Then, plasma malondialdehyde, total oxidant and antioxidant status were measured and also axonal and myelin changes in sciatic nerves of histopathological examination were performed. The data were analyzed by Kolmogorov Smirnov test, Mann-Whitney U-test, and Chi square test. p <.05 was considered statistically significant. RESULTS: The proximal and distal latency difference were higher and nerve conduction velocity were lower in SNI group than C and O groups, and the myelin structure was found to be broken in group SNI compared to groups C and O. However, the amplitude of the compound action potential, the nerve conduction velocity were significantly higher in group SNI + Ozone than in group SNI. Moreover, myelin injury was significantly lower in group SNI + Ozone compared to group SNI. Total oxidant status in group SNI was significantly higher than in groups C, O, and SNI + Ozone. But, total antioxidant status in group SNI was significantly lower than in groups C, O, and SNI + Ozone. CONCLUSION: This study showed that the administration of ozone at a dose of 0.5 mg/kg after peripheral nerve injury in rats reduces myelin and axonal injury.

Predicting critical duration and reversibility of damage in acute mesenteric ischemia: An experimental study.

BACKGROUND: The objective of the current study was to investigate the value of the ischemic biomarkers endothelial cell-specific molecule-1 (endocan) and signal peptide-CUB-EGF domain-containing protein-1 (SCUBE-1) in the diagnosis and assessment of earlystage and irreversible damage in acute mesenteric ischemia. METHODS: An experimental mesenteric ischemia reperfusion model was designed using 54 rats. Nine groups were created: Three sham groups [Groups I (30th minute), IV (2nd hour), and VII (6th hour)], in which only blood and tissue specimens were sampled; 3 ischemia groups [Groups II (30th minute), V (2nd hour), and VIII (6th hour)], in which blood and tissue specimens were sampled after ligation of the superior mesenteric artery (SMA); and 3 reperfusion groups [Groups III (30th minute), VI (2nd hour), and IX (6th hour)], in which blood and tissue specimens were sampled after declamping the SMA and reperfusion for 1 hour. SCUBE-1 and endocan samples obtained from blood and tissue were examined histopathologically. RESULTS: The SCUBE-1 level was higher in the ischemia groups when compared with the sham groups (p<0.05), and the endocan level was markedly different in the late ischemia (6th hour) group. When these 2 markers were used together to assess irreversible mesenteric damage in the histopathological examination, the sensitivity in distinguishing between reversible or irreversible damage was 94.1% with a specificity of 73.7%. CONCLUSION: The elevation of SCUBE-1 alone seems to be significant for predicting early mesenteric ischemia in laboratory rats. The combination of SCUBE-1 and endocan may be useful to detect irreversible intestinal damage.

Common Methylenetetrahydrofolate Reductase Polymorphisms (A1298C & C677T) in Ectopic Trophoblasts and Methotrexate Treatment Failure in Tubal Pregnancies.

OBJECTIVES: The success rate of methotrexate (MTX) therapy varies among tubal ectopic pregnancies. Common methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T&A1298C) have been suggested to alter MTX effect. This study aimed to assess and compare MTX treatment failure rates with respect to MTHFR polymorphisms in trophoblasts of ectopic tubal pregnancies. MATERIAL AND METHODS: A retrospective chart review of tubal ectopic pregnancies was conducted and 34 eligible cases were found. Paraffinized blocks of ectopic trophoblastic tissues were retrieved from the archives of pathology department. Common MTHFR polymorphisms were studied on microdissected trophoblastic tissues. Sixteen cases with history of failed MTX therapy (study group) and 18 control cases were compared for their pertinent clinical characteristics and common MTHFR polymorphisms (C677T&A1298) data. RESULTS: In the study group, there were 8 (50%) C677T single nucleotide polymorphisms (SNP) and 9 (56.7%) A1298C SNP. Polymorphism rates were not found to be different between two groups for neither polymorphism (p > 0.05 for both). Number of compound heterozygotes was 3 (18.7%) in study group and 5 (27.7%) in controls (p = 0.693). In addition, MTHFR polymorphism presence seemed to have no effect on interval serum ß-hCG concentration change in MTX-fail group (p=0.693). CONCLUSIONS: Our data implied that common MTHFR polymorphisms of ectopic trophoblastic tissue are not associated with MTX failure in patients with tubal pregnancies. Additionally, serum ß-hCG concentration changes caused by MTX treatment and studied MTHFR polymorphisms are likely independent.

Effect of Methyl Palmitate on the Formation of Epidural Fibrosis in an Experimental Epidural Fibrosis Model.

AIM: To investigate the effects of local and systemic administration of methyl palmitate on the formation of epidural fibrosis. MATERIAL AND METHODS: Twenty-eight rats were randomly divided into four equal groups (control, Spongostan, local methyl palmitate and orally methyl palmitate) and laminectomy was performed between T11 and L1 in all rats. Local methyl palmitate (300 mg/kg) was applied with Spongostan; methyl palmitate (300 mg/kg) was given orally three times per week on different days for a total period of 4 weeks. Four weeks later, the vertebral column from T9 to L3, including the paraspinal muscles and epidural scar tissue, was removed en bloc and epidural fibrosis and arachnoidal involvement was graded and evaluated histopathologically. Kruskal-Wallis and Pearson Chi-Square test were used for statistical analysis. A statistically significant p-value was determined as p < 0.05. RESULTS: The grading of epidural fibrosis was lower at a statistically significant level in orally-administrated methyl palmitate groups compared to the control and spongostan groups (p < 0.05). CONCLUSION: The findings of this study show that oral methyl palmitate decreases the formation of epidural fibrosis and that this effect of methyl palmitate could be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, including anti-inflammatory and antioxidant effects.

Effect of systemic application of bone marrow-derived mesenchymal stem cells on healing of peripheral nerve injury in an experimental sciatic nerve injury model.

AIM: To investigate the effects of systemic application of bone marrow-derived mesenchymal stem cells in a compression model of peripheral nerve injury. MATERIAL AND METHODS: 24 male Wistar albino rats were randomly divided into 3 equal groups (n=8):Control (C),injury (I),and stem cell and injury (SI).The sciatic nerve of rats in the I and SI groups was subjected to clip compression for 5 minutes.Moreover,approximately 5x105 bone marrow-derived mesenchymal stem cells were given via tail vein of the rats in the SI group immediately after clip compression. The nerve conduction velocities and amplitudes of the rats were measured 30 days later.Then,the sciatic nerves were removed, and myelin damage grading and axon counting were performed.The data were analyzed by One-Way ANOVA and Tukey\'s post-hoc test.P values less than 0.05 were considered to be statistically significant. RESULTS: While the proximal,distal and mean latency values were higher in the I and SI groups than in the control group,the same measurements were lower in the SI group than in the I group.While the nerve conduction velocity,the compound action potential and the number of axons were lower in the I and SI groups than in the control group,the same measurements were higher in the SI group than in the I group.Moreover,myelin damage was found to be lower in the SI group than in the I group. CONCLUSION: It has been shown that systemic application of bone marrow-derived mesenchymal stem cells in a compression model of peripheral nerve injury has a positive impact on both myelin sheath and axon survival.