Clinicopathological significance of mutation profile detected by next generation sequencing in different metastatic organs of non-small cell lung cancers.

BACKGROUND: The primary tumor and it's metastases show heterogeneity in molecular studies for targeted therapies in Non-Small Cell Lung Cancer(NSCLC), the leading cause of cancer-related deaths worldwide. The study aimed to identify somatic mutations in biopsies from NSCLC patients' metastatic organs using Next-Generation Sequencing(NGS) and examine their association with clinicopathological parameters. MATERIALS AND METHODS: The study included 128 NSCLC patients and, NGS was performed on tumor biopsies from different metastatic organs at Molecular Pathology laboratory of the Department of Medical Pathology in Aydin Adnan Menderes University Faculty of Medicine. The age, gender, histopathological diagnoses, metastatic organs, smoking and mutation status were all recorded, along with the analysis results of 72 genes and 4149 primers in the panel of the NGS system. RESULTS: 53.9 % of the cases had a history of smoking and patients with brain metastases had a higher smoking rate(p=0.000). The most common occurrence(39.8 %) was lymph node metastasis, followed by brain(19.5 %). There was a strong correlation between mutation presence and metastasis in the liver(p=0.012), bone(p=0.002), and pleura(p=0.008). Smokers had a higher frequency of KRAS(p=0.000) and TP53(p=0.001) mutations. Brain metastases showed a statistically significant NF1 mutation(p=0.001), while the liver exhibited a significant BRAF mutation(p=0.000). NF1-TP53, PTEN-TP53 and NF1-PTEN were the most common concomitant mutations and, the brain was the most common metastatic organ in which they occurred. CONCLUSION: Our results suggest prizing assessing detected mutations, in the prediction, follow-up and management of metastases, especially in patients with lung adenocarcinoma. The assessment also needs to consider the tumor's mutation status in metastatic organs. New therapeutic agents targeting NF1 mutations will be available in the future to treat NSCLC, especially in metastases.

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases.

Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(-), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(-)/PgR(-) 23.49%, ER(+)/PgR(-) 10.74%, and ER(-)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

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.

A Rare Nephrotic Syndrome Related to Chronic Lymphocytic Leukemia: Focal Segmental Glomerulosclerosis.

Chronic lymphocytic leukemia (CLL) is a hematological disease characterized by the proliferation of monoclonal B-lymphocytes. Although autoimmune complications such as autoimmune hemolytic anemia and immune thrombocytopenia are common in CLL patients, nonhematological autoimmune complications are rather rare. The most common renal involvements are membranoproliferative glomerulonephritis and minimal change disease. Focal segmental glomerulosclerosis (FSGS) is predominantly associated with Hodgkin's lymphoma among hematological malignancies. FSGS associated with CLL is rarely reported in the literature, with a poor understanding of the common pathophysiology and a very limited experience with this co-occurrence. Although Rai Stage 1/Binet Stage B CLL, our 61-year-old case, who was diagnosed with secondary FSGS, which is a very rare complication, was treated with fludarabine, cyclophosphamide, and rituximab (FCR) combination. Following the treatment, a complete response was achieved about CLL, and the patient, whose renal findings recovered, is in remission and under follow-up for six years. Although the mechanisms between CLL and autoimmune complications are not fully elucidated, it is usually related to immune disorders like an abnormal T-cell response and polyclonal antibody production. While FSGS is very rare in lymphoma, its co-existence with CLL is reported only in a limited number of case reports. Steroids may be used in these patients; however, in cases not responding to steroids, treatment of the underlying CLL is required.

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.

Gut mucosa in the rats exposed temporary mechanical obstruction fed with probiotic.

BACKGROUND: Created a model in the rats, to prevent mucosal damage and related effects in the patients, who were operated due to mechanical obstruction. Some groups fed fodder with probiotics, some groups fed with standard fodder. It is objected that the damage of gut mucosa and related effects on how to expose the differences of the groups. METHODS: In this study, 48 female Wistar-albino type rats are separated into five groups randomly. In the first operation, rats' terminal ileum was tied up with silk except for the control group. Two groups 24, the other two groups 48 hours later operated again and terminal ileum obstructions were removed. During that time, each one of those 24 and 48 hours of obstructed groups were fed with probiotic. Twenty-four hours later, the control group and other groups were operated for the third time for sampling. Terminal ileum, liver, spleen, MLN (Mesenteric lymph node) and blood samples were taken. RESULTS: The research group, which was obstructed and fed with probiotics during 48 hours, was significantly observed in increased mucosa cell loss and mucosal edema. Bacterial translocation was found more common in groups without probiotics. Tissue GR (Glutathione reductase) and erythrocyte CAT (Catalase) were lower in the group of 24 hours obstructed and given probiotics. CONCLUSION: The findings suggest that the high rate of mucosal edemas in the groups that are fed with probiotics can be seen as damage, but we think that probiotics are consonant with the strength of the mucosal barrier. Thus, in the groups fed with probiotics, it is possible that bacterial translocation is seen less, and some antioxidative enzymes are found less. Further studies are needed to investigate the benefits of probiotics in patients operated for obstruction.

Efficacy of thymoquinone in the treatment of experimental lipopolysaccharide-induced acute lung injury.

INTRODUCTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are acute onset syndromes affecting the lungs, which develop for several reasons and are characterized by hypoxemia and diffuse lung infiltration. The activity of thymoquinone (TQ) is known in acute lung injury. It is considered that it could be effective in ALI/ARDS treatment by ensuring possible COX-2 inhibition. AIM: By this study was to show the protective activity of TQ in lipopolysaccharide (LPS) induced acute lung injury.Material and methods: A total of 28 BALB/c male mice were randomized to 4 groups of 7 as the Control group, TQ group (3 mg/kg), LPS group (5 mg/kg) and TQ treatment group. TQ was administered intraperitoneally 1 hour before the intratracheal administration of LPS (5 mg/kg). The mice were sacrificed 6 hours after the LPS administration and the lungs were extracted for histopathological examination. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of Dokuz Eylul University. RESULTS: When all the study groups were compared, significant differences were found between the groups in terms of the degrees of neutrophil migration (p = 0.042), intra-alveolar hemorrhage (p = 0.004) and alveolar destruction (p < 0.0006). A significant recovery was observed in the lung histopathological changes (neutrophil migration, intra-alveolar hemorrhage and alveolar destruction) in the TQ treatment group. CONCLUSIONS: The results of this study showed that TQ may have a protective effect against LPS-induced acute lung injury. The possible mechanism could be considered to be cyclooxygenase 2 (COX-2) inhibition.

The correlation of prognostic biomarkers (Ki-67, Bcl-2, HIF-1α, cyclin D1) with metabolic tumor volume measured by F-FDG PET/CT inlaryngeal cancer.

OBJECTIVES: To investigate the correlation between tumor stage, Ki-67, Bcl-2, hypoxia inducible factor-1α (HIF-1α), cyclin D1 and metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax) measured by 18F fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients diagnosed with laryngeal cancer. PATIENTS AND METHODS: In this study, included 25 consecutive laryngeal cancer patients (2 women, 23 men) diagnosed and treated in the Otorhinolaryngology Department of our tertiary care center. All cases underwent 18F FDG PET/CT and SUVmax, mean standardized uptake value, MTV, and TLG values were calculated. Tumor staging was made and immunohistochemical staining was carried out for Ki-67, Bcl-2, HIF-1α and cyclin D1. RESULTS: Eight (32%) patients had glottic laryngeal cancer, 6 (24%) had supraglottic laryngeal cancer and 11 (44%) had transglottic laryngeal cancer. Cyclin D1 was significantly correlated with MTV (r = 0.45, P = 0.03), TLG (r = 0.492, P = 0.01) and T-stage (r = 0.483, P = 0.02). Bcl-2 was significantly correlated with SUVmax (r = -0.41, P = 0.05) and tumor stage (r = -0.442, P = 0.03). MTV and TLG are significantly correlated with nodal stage (r = 0.422, P = 0.04, r = 0.419, P = 0.04), while TLG (r = 0.403, P = 0.05) and SUVmax (r = 0.440, P = 0.03) were correlated with tumor stage. CONCLUSION: Our results indicated that biomarkers such as cyclin D1 and Bcl-2 were correlated with measures such as MTV, TLG, and SUV in 18F-FDG PET/CT. Integrative and combined evaluation of biomarkers and imaging data derived from 18F-FDG PET/CT are important for staging and appropriate management of patients with laryngeal cancer.

Vitamin D Receptor Level in Biopsy Specimen of Patients with Ulcerative Colitis: Results from a Center in Western Anatolia.

BACKGROUND: Ulcerative colitis (UC) is a chronic, inflammatory bowel diseases characterized by uncontrolled inflammatory condition of the colon and rectal mucosa marked by recurrent periods of remission and exacerbation. Vitamin D receptor (VDR) is a member of the steroid receptor family that mediates the effects of vitamin D by regulating transcription of multiple cellular genes. We aimed to evaluate vitamin d receptor level in biopsy specimen of patients with UC in this study. METHODS: VDR levels were retrospectively studied in colon biopsy specimens of UC patients. The Spearman's rho correlation analysis, The Kolmogorov-Smirnov, Mann Whitney U, and chi-square tests were used for statistical analysis. The p values below 0.05 were considered statistically significant. RESULTS: Study included 112 UC patients (65 male and 47 female) and 30 controls (19 female and 11 male) who had normal results in biopsy examinations carried out due to various reasons. VDR levels of UC patients were statistically lower than control subjects, and was not associated with duration of the disease and place of involvement. CONCLUSIONS: VDR is an important receptor in the pathogenesis of UC, and optimizing vitamin D levels could have a therapeutic role in UC.

Effect of Pycnogenol® on an experimental rat model of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis (AC) is a frequent and challenging disease in ophthalmology practice. Cell protective effect of Pycnogenol® (PYC) depends on its antioxidant and anti-inflammatory properties. The aim of the study is to investigate the effect of PYC on an experimental AC model. METHODS: Ovalbumin and Al(OH)3 were given seven times intraperitoneally (i.p.) every other day and ovalbumin installed everyday directly on conjunctiva to create an AC rat model. Then, PYC (3 or 10 mg/kg i.p.) was applied in the study groups. Control rats were given adjuvant Al(OH)3 i.p. and topical saline on conjunctiva. A negative control group in which only PYC (10 mg/kg/7 days) was administered i.p. and an AC positive control group which have been given dexamethasone (1 mg/kg/7 days) was created. Mast cells were counted with a microscope; histological evaluation was performed with H-E and toluidine blue, mast cell tryptase, and TNF-α and TGF-ß staining. RESULTS: Pycnogenol treatment alone did not show any detrimental effect. Mast cell count (MCC) decreased in both dexamethasone and 10 mg/kg given PYC treatment groups compared to positive control group and these results were statistically significant (MCC 1.85 ± 0.69, p < 0.001; 2.42 ± 0.53, p = 0.003). Negative staining with TGF-ß and weak focal staining with TNF-α were the common findings of dexamethasone and PYC treatment groups. CONCLUSIONS: The animal model of AC was successfully developed by using aforementioned way. PYC is a safe herbal product and it has alleviated the findings of ovalbumin-induced AC-similar to dexamethasone-histologically in this experimental model. These results are promising for the future of AC treatment.

Effects of Topical Thymoquinone in an Experimental Dry Eye Model

Objectives: To comparatively evaluate the effects of thymoquinone (TQ), the biologically active main component of volatile oil derived from Nigella sativa seeds, in an experimental dry eye model. Materials and Methods: A total of 36 BALB/c mice 10 weeks of age were used in the study. The mice were divided into 6 groups of 6 mice. Two groups were negative and positive controls, and the other 4 groups were treated with balanced salt solution, fluorometholone (FML), TQ, or vehicle (Tween80). After 1 week of treatment, the mice were killed and the eyes removed for histopathologic examination and cytokine analysis. Interleukin (IL)-1α tumor necrosis factor-α, interferon-γ, IL-2, IL-6, IL-10, and lactoferrin levels in the conjunctival tissue were measured by multiplex immunobead assay. The presence of inflammatory cells in ocular tissue samples were investigated by hematoxylin-eosin and periodic acid-Schiff staining. Inflammatory T cells containing CXT receptor in the conjunctiva were determined by flow cytometry. Results: FLML and TQ groups had less inflammatory cell density and more goblet cells compared to the other groups. High levels of IL-1α and IL-2 were found in the TQ group. Conclusion: TQ treatment was associated with reduced inflammation in pathological examination, but did not significant lower cytokine levels.

The effect of ozone treatment on remote organ myocardial injury in an aortic ischemia-reperfusion model.

BACKGROUND: This study aims to investigate the effect of ozone on myocardial ischemia-reperfusion injury occurring after occlusion - reperfusion of infrarenal abdominal aorta in rats. METHODS: Thirty-two Wistar albino rats (weighing 200-250 g) were randomized into four equal groups. The control (sham) group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Intraperitoneal ozone was applied for 10 days 1 mg/kg/day in the control+ozone group. Afterwards, control+ozone group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. Aortic ischemia-reperfusion and aortic ischemia-reperfusion+ozone groups underwent dissection of the infrarenal abdominal aorta, followed by achieving ischemia and reperfusion by cross-clamping the infrarenal abdominal aorta for 60 minutes and removing the cross-clamp for 60 minutes, respectively. The tissue levels of malondialdehyde and activity levels of superoxide dismutase, catalase, and myeloperoxidase were measured in the myocardial specimens. The tumor necrosis factor, interleukin-6 and troponin-I levels were measured in the plasma. A histopathological examination of the myocardial specimens was undertaken. RESULTS: Biochemical analysis showed that aortic ischemia-reperfusion significantly increased (p<0.05 vs. control) while ozone significantly decreased (p<0.05 vs. aortic ischemia-reperfusion) the myocardial tissue levels of superoxide dismutase and catalase and level of plasma troponin-I. Histologically, in the aortic ischemia-reperfusion group, myocardial disorganization, myofiber swelling and myofiber eosinophilia in the myocardial tissue samples were significantly increased compared to the control group (p<0.05 vs. control). However, histopathological changes in the aortic ischemia-reperfusion+ozone group decreased compared to the aortic ischemia-reperfusion group. CONCLUSION: The results of this experimental study indicate that ozone attenuates myocardial injury and oxidative stress that develop after infrarenal aortic ischemia-reperfusion through three markers; (i) decreased tissue superoxide dismutase and catalase levels, (ii) d ecreased p lasma t roponin-I l evels, a nd (iii) reduced histopathological changes, albeit not statistically significant.

Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

OBJECTIVES: Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. METHODS: The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 µmol/L/h. RESULTS: A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m2, 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 µmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 µmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). CONCLUSION: Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

Antibiotics in eosinophilic chronic rhinosinusitis: Rethinking maximal antimicrobial medical therapy.

OBJECTIVES/HYPOTHESIS: Eosinophilic chronic rhinosinusitis (eCRS) has recently been recognized as a CRS subtype characterized by inflammation rather than chronic infection. Consequently, the role of antibiotics as a component of maximal medical therapy for eCRS has been called into question. The purpose of this study was to investigate whether the use of antibiotics, which lack any secondary anti-inflammatory properties, are useful in the treatment of eCRS. STUDY DESIGN: Prospective individual cohort study. METHODS: Institutional review board-approved, prospective study of 39 patients presenting with chronic rhinosinusitis (CRS). In all patients, Lund-Kennedy endoscopy scores, Lund-Mackay computed tomography scores, and Sino-Nasal Outcome Test-22(SNOT-22) scores were obtained before and after treatment with amoxicillin-clavulanic acid twice a day (625 mg) for 4 weeks. Patients were subsequently stratified into eCRS and non-eCRS groups based on having over 10 eosinophils per high-power field by histopathological examination. The efficacy of antibiotic therapy was compared between groups using the nonparametric Mann-Whitney U test. RESULTS: Within the non-eCRS group (n = 14), there was a significant improvement in both the Lund-Mackay score (P = .002) and SNOT-22 score (P < .001) but not the endoscopy score. Among the eCRS patients (n = 25), the Lund-Mackay score was similarly improved (P = .007); however, there was no significant improvement in the endoscopy or SNOT-22 scores. CONCLUSIONS: The use of antibiotics without independent anti-inflammatory properties have limited efficacy in patients with eCRS. The concept of maximal medical therapy using antibiotics must continue to evolve in the setting of new evidence for inflammatory subtypes of CRS. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:794-796, 2017.

Inhibitory Effect of Pycnogenol® on Airway Inflammation in Ovalbumin-Induced Allergic Rhinitis.

BACKGROUND: The supplement Pycnogenol® (PYC) has been used for the treatment of several chronic diseases including allergic rhinitis (AR). However, the in vivo effects on allergic inflammation have not been identified to date. AIMS: To investigate the treatment results of PYC on allergic inflammation in a rat model of allergic rhinitis. STUDY DESIGN: Animal experimentation. METHODS: Allergic rhinitis was stimulated in 42 rats by intraperitoneal sensitization and intranasal challenge with Ovalbumin. The animals were divided into six subgroups: healthy controls, AR group, AR group treated with corticosteroid (dexamethasone 1 mg/kg; CS+AR), healthy rats group that were given only PYC of 10 mg/kg (PYC10), AR group treated with PYC of 3mg/kg (PYC3+AR), and AR group treated with PYC of 10 mg/kg (PYC10+AR). Interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), and OVA-specific immunoglobulin E (Ig-E) levels of serum were measured. Histopathological changes in nasal mucosa and expression of tumor necrosis factor-α (TNF-α) and IL-1ß were evaluated. RESULTS: The levels of the IL-4 were significantly decreased in the PYC3+AR, PYC10+AR and CS+AR groups compared with the AR group (p=0.002, p<0.001, p=0.006). The production of the IFN-γ was significantly decreased in the PYC3+AR and PYC10+AR groups compared with the AR group (p=0.013, p=0.001). The administration of PYC to allergic rats suppressed the elevated IL-10 production, especially in the PYC3+AR group (p=0.006). Mucosal edema was significantly decreased respectively after treatment at dose 3 mg/kg and 10 mg/kg PYC (both, p<0.001). The mucosal expression of TNF-α has significantly decreased in the PYC3+AR and PYC10+AR groups (p=0.005, p<0.001), while the IL-1ß expression significantly decreased in the CS+AR, PYC3+AR, and PYC10+AR groups (p<0.001, p=0.003, p=0.001). CONCLUSION: PYC has multiple suppressive effects on allergic response. Thus, PYC may be used as a supplementary agent in allergic response.

Acute kidney injury after near drowning: The way from the beach to hemodialysis.

Acute kidney injury (AKI) occurs in many different situations and may have a variable prognosis influenced by clinical setting, underlying cause, and comorbidity. This is important because of the high mortality and morbidity risk affecting many people around the world. Near-drowning related AKI requiring hemodialysis is very seldom reported in literature. Although cardiovascular and respiratory disorders are more frequently seen after this entity, we aimed to emphasize this rare but dangerous complication in near-drowning patients.

H. pylori positivity and various pathological, endoscopic and clinical features correlated with each other.

OBJECTIVE: To investigate the relationship between dyspepsia symptom scores and endoscopic appearances, and histopathological findings and helicobacter pylori positivity in patients having dyspepsia symptom. METHODS: The study was conducted at the gastroenterology outpatient clinic of Adnan Menderes University, School of Medicine, Aydin, Turkey from April 2012 to July 2012 and comprised patients between 18-65 years of age who were admitted with dyspepsia. Glasgow dyspepsia severity scoring was done with questions posed orally to the patients. In histopathological evaluation of biopsy specimens according to Sydney criteria, chronic inflammation, activity, atrophy, intestinal metaplasia and helicobacter pylori parameters were used. Total number of eosinophils and number of mast cells were recorded. RESULTS: Of the 60 patients with dyspepsia, 38(63.3%) were female and 22(36.7%) were male. The degree of activation and severity of inflammation increased significantly with increasing helicobacter pylori positivity(r=0.459'p<0.0001; r=0.475'p<0.0001). A significant relationship was found between inflammation, activation and the number of mast cells (p<0.05).There was no relationship between helicobacter pylori intensity and the eosinophil count (r=0.171; p=0.093). There was also a statistically significant correlation between severity of inflammation and activation and the number of eosinophils (r=0.313;p=0.002;r=0.245;p=0.016). CONCLUSIONS: Mast cell density was seen to have a role in the inflammatory processes of helicobacter pylori infection.

Gastric involvement of sarcoidosis in a patient with multiple lung nodules.

Sarcoidosis is a granulomatous disorder mostly could involve intrathoracic structures. The gastric involvement is rare and the symptoms may be non-specific. We herein report a case of a 56-year-old female patient who was admitted due to chest tightness and discomfort. Computed tomography (CT) of the thorax revealed bilaterally nodular lesions in the lower lobes of the lung and pleural effusion on the left side. Positron emission tomography/CT showed lung nodules and gastric involvement with mesenteric lymphadenomegalies with pathological uptake of 18F-fluoro-2-deoxy-d-glucose. Pathological examination of the lung biopsy taken by thoracotomy demonstrated non-caseating granulomas. The gastric biopsies taken by endoscopy also showed non-caseating granulomas consistent with a diagnosis of sarcoidosis.

Nuclear Factor Kappa B, Matrix Metalloproteinase-1, p53, and Ki-67 Expressions in the Primary Tumors and the Lymph Node Metastases of Colorectal Cancer Cases.

Colorectal cancer (CRC) is the third most frequent malignancy. Many factors such as NF-κB, matrix metalloproteinase-1 (MMP-1), p53, and Ki-67 are likely to be involved in its development and progression. Lymph node metastases indicate increased tumor burden and tumor cell heterogeneity and affect both the treatment strategies and the prognosis. In this study, expressions of NF-κB, MMP-1, p53, and Ki-67 were between the primary tumors and lymph node metastases in 110 Dukes' stage C, CRC cases by immunohistochemical methods, related to patients' clinical outcomes. NF-κB, p53, and Ki-67 expressions were significantly higher in the metastatic lymph nodes compared to the primary tumor tissues (P = 0.04, P = 0.04, and P = 0.01, resp.). In the metastatic lymph nodes NF-κB expression was correlated with both p53 (r = 0.546, P = 0.003) and Ki-67 (r = 0.586, P = 0.0001) expressions. The univariant and multivariant analyses showed that only "pT stage" preserved an independent prognostic significance for recurrence-free survival rates and 5-year overall survival rates (P < 0.001 for both). Metastatic cells can acquire different biological characteristics compared to their primaries. Elucidation of properties acquired by metastatic cells is important in order to better determine prognosis, reverse drug resistance, and discover new treatment alternatives.