Prognostic and predictive significance of GITR in metastatic renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) has gradually increased in recent years. There have been significant developments in metastatic RCC in recent years with the introduction of immune control point inhibitors. Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) is a co-stimulatory molecule and is seen in the highest amounts in activated CD4+ T lymphocytes and CD8+ T lymphocytes, forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg). GITR leads to an increase in interleukin (IL)-2 and CD25 and Interferon Gamma. It shows an anti-tumoural effect by inhibiting the suppressive functions of FOXP3+ regulatory cells (Treg). Therefore, we aimed to evaluate the prognostic and predictive effect of GITR, tumor-infiltrating lymphocytes (CD4+CD8) (TIL), and FOXP3 in patients with metastatic RCC. PATIENTS AND METHODS: Patients diagnosed with pathologically confirmed metastatic renal cancer between 2016 and 2021 were included in our study. Clinicopathological features and some laboratory tests were recorded. GITR, CD4, CD8, and FOXP3 were evaluated by immunohistochemistry (IHC) from biopsies or nephrectomy material and recorded. RESULTS: The study included 41 patients. The median progression-free survival (PFS) was 10.5 months, and the median overall survival (OS) was 13.9 months. Median PFS was 7.9 months for the GITR-low group and 18.9 months for the GITR-high group. Median PFS was statistically significant and longer for the GITR-high group than the GITR-low group (p=0.003). When patients who received nivolumab in the 2nd line were evaluated, median PFS was found to be 5.7 months in the GITR-low group and 15.7 months in the GITR-high group. Median PFS was statistically significantly higher in the GITR-high group than in the GITR-low group (p=0.026). CONCLUSIONS: In patients with metastatic RCC, higher GITR was associated with better PFS. At the same time, in patients using nivolumab, better PFS was seen in the GITR high group. If supported by prospective studies, GITR can be used as both a prognostic and predictive marker.

Monitoring of near-infrared spectrum values during packed red blood cell transfusion in pediatric intensive care unit.

OBJECTIVES: Packed red blood cell (PRBC) transfusion is one of the most common treatment options in pediatric intensive care unit (PICU) which targets a better cerebral oxygenation. This study aimed to show the cerebral near-infrared spectroscopy (cNIRS) changes during PRBC transfusions in PICU. MATERIAL AND METHODS: In this prospective observational study, changes in regional cerebral tissue oxygen saturation (rSO2) in pediatric patients, who required PRBC transfusion were monitored. All the cNIRS and related values were classified as baseline values. The same values were measured and calculated at the end of transfusion and named as 4th-hour values. Further measurements and calculations were made three hours later and named as 7th-hour values. Changes in cNIRS, cerebral tissue fractional oxygen extraction (CTFOE), cNIRS variability index (cNIRS-VI) were compared using Friedman test. RESULTS: A total of 53 PRBC transfusions were monitored. Baseline haemoglobin increased from 6.3 (5.9, 6.7) gr/dL to 8.6 (8.4, 9) gr/dL at the 7th-hour. cNIRS values improved during transfusion (P=0.012), with a concomitant decrease in cNIRS-VI and CTFOE values (P<0.001 and P=0.017 consecutively) CONCLUSION: Our study revealed that there is an increase in cNIRS and related values after transfusion compared to baseline values in critically ill children admitted to a PICU. Age of PRBC did not have an effect on delta-cNIRS or post-transfusion hemoglobin values. There is a moderate correlation between the baseline cNIRS values and delta-cNIRS value after the transfusion.

Effect of Potassium Nitrate and Boric Acid on the Bond Strength of Veneering Ceramics to Zirconia.

In this study, the effects of boric acid addition to the veneer ceramics and treatment of the ceramic cores immersed in potassium nitrate solution were evaluated to reduce the micro cracks that may occur in the internal structure of the ceramic, increase the mechanical properties and improve the chemical bonding strength of core ceramics. In the data obtained after the experiment, the average MPa values showed statistically significant differences according to the groups (p⟨0.001). The average value in the control group (C) was lower than the others. There was no statistically significant between the mean values of the boric acid application in the veneer ceramic (IB) group and zirconia core immersed in the potassium nitrate solution (IN) group. The highest mean values were observed between the veneer ceramic and the zirconia core by application of boric acid and potassium nitrate (IBN) group. As a result potassium nitrate and boric acid application affects the bond strength between zirconia core and veneer ceramic and increases mechanical properties of ceramics.

Polymorphisms of eNOS, catalase, and myeloperoxidase genes in prostate cancer in Turkish men: preliminary results.

Prostate cancer (PCa) is the most common type of neoplasm in European males. Genetic and epigenetic factors contribute to PCa development and progression. In this study, we aimed to assess the relationship between PCa and polymorphisms in the genes encoding endothelial nitric oxide synthase (eNOS), catalase (CAT), and myeloperoxidase (MPO). In total, 193 patients were included in the study. Patients were divided into three groups: PCa (78), benign prostate hyperplasia (40), and control males (75). The parameters assessed included body mass index (BMI), smoking habits, presence of prostatism, prostate-specific antigen (PSA) levels, Gleason scores of prostate specimens, as well as polymorphisms in eNOS-G894T, CAT- 262T, and MPO G-463T genes. BMI and smoking status of controls and patient groups showed no significant difference. CAT-262T gene polymorphism was found to be homozygous in 35.4% of PCa patients, which was 4.02-fold that in the controls (P = 0.006). There was no statistically significant difference in eNOS-G894T and MPO G-463T gene polymorphisms between any of the groups. In conclusion, we found catalase levels to be associated with PCa diagnosis and PSA value. We did not find any significant differences between groups for other polymorphisms, but we believe that further studies with a large sample size may be needed before drawing definite conclusions.

The efficacy of tissue factor -603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients.

UNLABELLED: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene -603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me-thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF -603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ2 or Fisher exact test, if appropriate. RESULTS: No differences were observed in the distribution of TF gene -603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p < 0.05). Difference in frequency of 677TT+CT (MTHFR) + 5466GG (TF) genotypes combination was found in women of two investigated Groups (p < 0.05). No differences were also in genotypes and allele frequencies of MTHFR C677T and PT G20210A between two Groups (p > 0.05). CONCLUSIONS: The present study did not show significant association of TF gene -603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.

A Rare Case of Hanhart Syndrome with Mild Developmental Delay.

Hanhart Syndrome (OMIM 103300) is an extremely rare syndrome with some congenital malformations. It is characterized by hypoglossia, adactylia/hypodactylia, peromelia of arms and/or legs and micrognathia. The severity of the symptoms can differ from patient to patient. Some affected individuals may have only a part of these clinical features. In this case report, we want to present a Turkish girl with hypoglossia, micrognathia and peromelia who was diagnosed according to the clinical and radiographic findings.

The effect of Glutathione-S-transferases in the susceptibility to bladder cancer.

BACKGROUND: Urinary bladder cancer is a quite common cancer type in men and women all over the world. Genetic polymorphisms of xenobiotic-metabolizing enzymes could increase individual susceptibility to various cancer types. AIMS: The aim of our study is to evaluate the rate of these polymorphisms in a group of patients from Central Anatolia. METHODS: Our study subjects consist of 65 men with histopathologically confirmed bladder TCC and 70 cancer-free control subjects. Restriction fragment length polymorphism (RFLP) method was used for the detection of polymorphisms of GSTT1 and GSTM1. RESULTS: There was no association between bladder cancer and GSTM1 polymorphism (ORs = 0.64, 95% CI = 0.32-1.29), but the probability of bladder cancer in patients with GSTT1 null genotype (67.9%), was significantly higher from the probability of bladder cancer with GSTT1 normal genotype (43.0%) statistically (ORs = 2.8, 95% CI = 1.16-6.75). CONCLUSION: Polymorphisms of these genes have been assessed to evaluate the relative risk of various cancers. Our intention is to continue this study with larger series of bladder cancer patients in a group of Turkish population from Central Anatolia.

HLA-B51 subtypes in Turkish patients with Behçet's disease and their correlation with clinical manifestations.

Behçet's disease (BD) is a multisystemic inflammatory disease believed to be triggered by microbial or environmental factors on a genetic platform. Clinically, it may have an impact on many body systems, including the mucocutaneous, ocular, articular, vascular, and neurological systems. In this study, we aimed to determine the HLA-B51 subtypes and their correlations with the clinical findings of BD. Fifty-one patients with BD and 44 gender- and age-matched healthy subjects were included in this study. The HLA-B51 subtypes of all participants were determined, and the correlations of the clinical manifestations of the disease with the HLA-B51 subtypes were analyzed. HLA-B51 positivity was found to be significantly higher in the patient group (P < 0.001, RR = 15.20), which had significantly more frequent HLA-B5101, HLA-B5102(01), HLA-B5109, and HLA-B5122 subtypes than the healthy subjects (all P < 0.05). Furthermore, considering the correlation between the genetic makeup and clinical findings, the HLA-B5109 subtype was found to be less frequent in patients with papulopustular skin lesions (P = 0.042). The frequency of HLA-B5103 was significantly higher in patients with central nervous system involvement (P = 0.015). There may be a relationship between HLA-B5102(01), HLA-B5109, and HLA-B5122 in addition to HLA-B51 and HLA-B5101(01) in Turkish patients with BD. The HLA-B5109 subtype can be protective against papulopustular lesion development; however, the HLA-B5103 subtype may pose a risk for neuro-Behçet development in BD.

Co-existence of familial Mediterranean fever and multiple sclerosis in two patients.

ABSTRACT Two female patients, aged 23 and 25 years-old diagnosed with Familial Mediterranean fever (FMF) were presented with ataxia and headache. Multiple sclerosis plaques were detected in their spinal and cranial MRI and diagnosis of multiple sclerosis was established. Genetic analysis demonstrated M694 V mutation (one homozygous and the other heterozygous) in both of the patients. Although it is quite rare, coexistence of familial Mediterranean fever and multiple sclerosis should be kept in the mind.

Effect of osteoblast cell culture on the bone implant contact.

PURPOSE: The aim of this study is to acquire an ideal bone implant contact under the cover of osteogenic effect of osteoblasts derived from Mesenchymal Stem Cells (MSCs). MATERIALS AND METHODS: Thirty dental implants were used for this study. Implants were placed in sheep mandibles and defects were created 4 mm coronally in the dental implants. These defects were filled with Platelet Rich Plasma (PRP) in one group and with PRP + Osteoblast Cell Culture (OCC) in another group. No procedure was conducted on the control group defects (empty defect group). Eight weeks later, osseointegration was investigated with Bone Implant Contact (BIC) measurements histomorphologically. Data were checked statistically. RESULTS: The variation of BIC rates between Empty Defect Group and PRP groups was significant (p <0.05). The BIC rate of the PRP group was higher than that of the Empty Defect Group. The variation of BIC rates between Empty Defect Group and PRP + OCC groups was significant (p <0.05). The BIC rate of the PRP + OCC group was higher than that of the Empty Defect Group. The variation of BIC rates between PRP and PRP + MSC groups was significant (p<0.05). The BIC rate of the PRP + OCC group was higher than that of the PRP group. At the end of the 8-week healing period, it was observed that the percentage of BIC was highest in the PRP + OCC group. CONCLUSIONS: Implant-bone connection was better in the OCC-PRP group compared with the PRP group and the empty defect group. The use of OCC-PRP combination was effective on healing. The BIC value was increased significantly by OCC.

Increased frequency of MEFV gene mutations in patients with primary dysmenorrhea.

OBJECTIVES: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and polyserositis and an autosomal recessive inheritance mode. Up to 15 % of FMF patients are reported to experience perimenstrual attacks. Primary dysmenorrhea could be an incomplete abdominal attack, or patients with dysmenorrhea may have increased frequency of MEFV gene mutation carriage. Therefore, we aimed to evaluate the frequency of MEFV gene mutations in patients with dysmenorrhea. METHODS: Eighty-four patients with primary dysmenorrhea attending consecutively to our gynecology department and 73 healthy female controls selected from hospital staff were included in the study, and MEFV gene mutations were analyzed. RESULTS: The prevalence of total allelic variants was significantly increased in dysmenorrhea patients (p = 0.015); analysis of individual variant rates revealed a significant increase in the frequency of MEFV gene mutations in dysmenorrhea patients compared with the control group (p = 0.036). CONCLUSION: Gynecologists and primary care physicians must be aware of FMF in the differential diagnosis of dysmenorrhea.

Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey.

Familial Mediterranean fever is a recessive autoinflammatory disease that is frequent in Armenians, Jews, Arabs, and Turks. The MEFV gene is responsible for this disease. We looked for MEFV gene variations (polymorphism and mutations) in a population that resides in Central Anatolia, Turkey. DNA was extracted from peripheral blood leukocytes of 802 familial Mediterranean fever patients. The DNA sequence data were examined for approximately 150 different mutations and polymorphisms, including single nucleotide polymorphisms in different exons of the MEFV gene. The male:female ratio of these patients was 1.44:1. Mutations were detected in 48.1% of the patients; 7.5% were homozygous, 11.1% were compound heterozygous and 31.5% had only one identifiable mutant allele. No mutations were detected in 51.9% of the patients. The main clinical characteristics of the patients were: abdominal pain in 20.6%, arthritis in 22.9% and amyloidosis in 4.6%. Sixty-six percent of patients had a family history of familial Mediterranean fever; 19.4% of the patients were found to have parental consanguinity. We conclude that the genetics of familial Mediterranean fever is more complex than has previously been reported; heterozygous patients presenting a severe phenotype should be further analyzed for less common secondary MEFV mutations, using gene sequencing.

An unusual cause of multiple cerebral hemorrhages: drotrecogin alpha (activated protein C).

The mortality of severe sepsis is still high, despite improved treatment modalities. It is known that treatment with DAA reduces mortality in this condition; however, major bleeding may occur as a complication. We present a patient with normal findings on platelet and coagulation tests who developed multiple cerebral hemorrhages after DAA infusion. Patients with septic shock who undergo DAA infusion should be followed closely for possible intracranial bleeding. When intracranial hemorrhage is detected in patients in the intensive care unit, treatment with DAA infusion should be questioned.

The azoospermia factor locus-c region was found to be related to Klinefelter syndrome in Turkish patients.

We looked for a possible association between Klinefelter syndrome (KFS) and microdeletions in the Y chromosome in Turkish KFS patients. We examined the frequency of KFS in male patients with proven non-obstructive azoospermia and the types of Y chromosome microdeletions in these KFS patients. Fifty azoospermic patients and 50 fertile men were included in this study. KFS was found in 14 azoospermic patients. Y chromosome microdeletions were found in eight KFS patients. Azoospermia factor locus c (AZFc) was the most commonly deleted interval in KFS patients. All KFS patients had elevated plasma follicle-stimulating hormone and luteinizing hormone concentrations, but they had normal plasma testosterone concentrations. Testis biopsy of five samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions were found in the fertile group. We concluded that there could be an association between the AZFc region and KFS. Screening for this should be part of diagnostic work-up, particularly in those considering assisted reproduction.

Genetic anomalies in patients with severe oligozoospermia and azoospermia in eastern Turkey: a prospective study.

Infertility is defined as the inability to conceive a child after one year of regular unprotected intercourse; it is a major health problem affecting about 10-15% of all couples. Infertility is due to a male factor in approximately 50% of cases. The human Y chromosome contains genes necessary for gonadal differentiation into a testis and genes for complete spermatogenesis. We examined the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions in 90 patients with severe male factor infertility and 75 fertile control men. Thirty of the infertile patients had nonobstructive azoospermia, 30 had oligozoospermia and 30 had normozoospermia. Five of 30 were azoospermic, four of 30 were oligozoospermic and two of 30 were normozoospermic with Y chromosome microdeletions. The AZFc locus was the most frequently deleted region (64%). Ten cases with azoospermia, four cases with oligozoospermia and four cases with normozoospermia had chromosomal abnormalities. The 75 men with proven fertility were genetically normal. We conclude that various chromosomal abnormalities and deletions of the Y chromosome can cause infertility; therefore, genetic screening is indicated for infertile patients.

A possible etiology of the internal derangement of the temporomandibular joint based on the MRI observations of the lateral pterygoid muscle.

The purpose of this study was to evaluate the relationship of the temporomandibular joint (TMJ) internal derangement and lateral pterygoid muscle (LPM) by magnetic resonance imaging (MRI). In this study, 115 subjects with TMJ internal derangement (total 230 TMJs) and 21 subjects without clinical symptoms (total 42 TMJs) were included. TMJ disc position and LPM were evaluated using MRI. LPM attachments were categorized into two different types: type 1, where fibers of the superior head of the LPM (SLPM) were attached to the disc and fibers of the inferior head of the LPM (ILPM) were attached to condyle, and type 2, where fibers of the SLPM were attached to the disc and condyle, and fibers of the ILPM were attached to condyle. The presence of muscle atrophy and degeneration were also evaluated. LPM attachments were observed in two different parts. Disc displacements were common in the muscle attachments of both types. Type 1 muscle attachments were seen in 85.9% of all the anterior disc displacement without reduction (ADD) TMJs (total 64 TMJs). Atrophy was seen in a higher proportion (43.7%) in TMJs with ADD (28/64) than in TMJs with normal and anterior disc displacement with reduction (ADDR). Out of 74 TMJs with atrophy, 68 had type 1 muscle attachment. Four TMJs had atrophy in both superior and inferior heads of the lateral pterygoid. However, atrophy was not present only in the ILPM. It has been concluded that since the SLPM only attached to the disc in type 1, the disc may displace anteriorly very easily. Therefore, this situation will reduce the function of the SLPM. Reduced muscle function may cause muscle atrophy. The activity of the SLPM may be more reduced since the disc permanently dislocated in TMJs with ADD. Finally, spasm of the LPM causes disc displacement and atrophy and then the degeneration of the LPM may follow disc displacement.

Changes in the mandibular angle in the dentulous and edentulous states.

STATEMENT OF PROBLEM: Reliable measurement of individual gonial angles is difficult because of the superimposed images appearing on the lateral cephalograms. However, this disadvantage is not encountered in orthopantomography. PURPOSE: This study determined whether the mean measurements of the mandibular angles of a group of totally edentulous patients were greater than those of unilaterally and posteriorly partially edentulous patients. Changes in the gonial angle between denture wearers and nondenture wearers in each group were also compared. MATERIAL AND METHODS: A total of 134 panelipse radiographs were used for measurements of mandibular angles. All radiographs used in this study were taken with the same panelipse machine by the same person. Of the 134 radiographs, 49 were of unilaterally and posteriorly partially edentulous adults and 85 were of totally edentulous adults. RESULTS: No significant differences were found between the mandibular angles when comparing partially edentulous and totally edentulous subjects. CONCLUSION: Within the limits of this study, there was no significant difference between the dentulous and edentulous states.