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Purpose: Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission., Methods: Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs., Results: Twenty-five patients, mean age 40.60 ± 14.04 years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1β were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1β, and TNF-α levels, but ET-1 increased (p = 0.011)., Conclusions: Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1β following remission of CS., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objectives: Our aim was to investigate the effects of endogenous chronic hypercortisolism on sleep electroencephalogram (EEG) and differences between the adrenocorticotropic hormone (ACTH)-dependent and independent Cushing Syndrome (CS) patients through a sleep spectral analysis program., Methods: A total of 32 patients diagnosed as having endogenous CS (12 ACTH-dependent and 20 ACTH-independent) and a control group comprising 16 healthy individuals were included in the study. Polysomnographic analysis was performed. Blood samples were collected at 08:00 AM for analysis of ACTH and basal cortisol, and at 00:00 AM for midnight cortisol levels. The frequency and power of the slow wave activity (SWA), theta, alpha, and beta waves of the first and last non-rapid eye movement (NREM) cycles were measured with a spectral analysis program., Results: The CS patient group had higher SWA power, especially in the first NREM cycle. In the ACTH-dependent group, SWA maximum and mean power values were higher in the frontal channels in the first NREM, compared to the last NREM sleep stage (p<0.05)., Conclusion: Cortisol has been found to be associated with SWA waves, making these waves higher in power, especially in the first NREM phase. This difference was much less pronounced in the final NREM sleep stage. The difference between the first and last NREM sleep stages with respect to the power of SWA in the frontal channel in the ACTH-dependent group suggests that not only cortisol but also high levels of ACTH affect the power of slow waves during sleep., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The aim of the present study was to evaluate the sleep parameters of patients with Cushing syndrome (CS) at the time of diagnosis and 12-months after treatment. Thirty four newly diagnosed patients with endogenous CS (17 with ACTH-secreting pituitary adenoma, 17 with adrenal CS) and 23 controls with similar age were included in the study. Two polysomnography (PSG) recordings were performed; one at the time of diagnosis and the other 12 months after resolution of hypercortisolemia. Control group had only baseline PSG. Based on the PSG findings, stage N2 sleep was found to be prolonged, stage N3 and REM sleep were shortened in patients with CS. Average heart rate and mean Apnea Hypopnea Index (AHI) score were higher in patients with CS than the control subjects. Sixteen (47.1%) patients with CS and 4 (17.4%) controls had obstructive sleep apnea (OSA; AHI ≥5). There were no significant differences in sleep parameters of patients according to the etiology of CS (adrenal vs. pituitary) patients. Following 12-months of treatment, a significant decrease in stage N2 sleep and a significant increase in stage N3 sleep were detected, but there was no change in terms of AHI. In conclusion, Cushing syndrome has disturbing effects on sleep structure and these effects are at least partially reversible after treatment. However, the increased risk of OSA was not reversed a year after treatment indicating the importance of early diagnosis and treatment of CS., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: We investigated newly diagnosed patients with endogenous CS for molecular changes in skin by biopsy before and a year after treatment of CS., Patients and Methods: 26 Patients with CS and 23 healthy controls were included. All the patients were evaluated before and a year after treatment. Skin biopsies were obtained from abdominal region before and a year after treatment in patients with CS and once from healthy volunteers. Total RNA was isolated from the skin biopsy samples and the real-time PCR system was used to determine the expression levels of 23 genes in the skin biopsy., Results: Skin expression levels of HAS 1, 2 and 3 mRNAs were lower and COL1A2, COL2A1, COL3A1 mRNAs were higher in patients with CS than in normal controls. MMP-9, TIMP-1 and elastin mRNA expression levels were similar in two groups. Skin IL-1β mRNA expression level was significantly higher in patients with CS. None of these parameters changed significantly 12 months after treatment. Patients with CS showed higher skin GH and HSD11B1 mRNA expressions and lower GHR and IGF-1R mRNA expression compared to control. Expression levels of IGF-1, GR and HSD11B2 mRNA were similar in two groups. None of these parameters changed significantly 12 months after treatment., Conclusion: CS is associated with increased expression levels of skin COL1A2, COL2A1, COL3A1 mRNAs (which are correlated with increased expression level of skin GH mRNA). Decreased skin HAS may cause decreased synthesis of HA that contributes to thinning of skin in CS. Increased local inflammatory cytokine and HSD11B1 mRNAs may be related to the acne formation in CS. Treatment of CS was not able to reverse these changes and ongoing changes were detected after treatment.

Introduction: We aimed to investigate the impact of first biological agents on second-line biological agents in kras wild-type metastatic colon patients in right and left colon., Patients and Methods: The patients received anti-EGFR compared with anti-VEGF in right and left colon separately according to progression-free survival and overall survival in second line., Results: A total of 84 patients were included in the study. In left colon, progression-free survival and overall survival were 9 and 14 months for anti-EGFR and 9 and 16 months for anti-VEGF in the second line. In right colon, progression-free survival and overall survival were 5 and 9 months for anti-EGFR and 4 and 6 months for anti-VEGF in the second line., Conclusions: Progression-free survival was higher in patients who received bevacizumab first followed by anti-EGFR than reverse sequencing in right colon. Overall survival was similar between two groups.

Purpose: Metastatic gastric cancer (mGC) is linked with worse prognosis, and tools are needed for predicting disease course and chemotherapy response. The value of the change in the neutrophil-to-lymphocyte ratio (NLR) during first-line palliative chemotherapy on the outcomes in patients with mGC is not fully explained. This study aimed to investigate the importance of changes in NLR in predicting disease course and chemotherapy response in mGC., Methods: We retrospectively reviewed 194 patients diagnosed with mGC between August 2005 and November 2016. The NLR was assessed before and after chemotherapy to evaluate its relationship with survival. According to threshold values determined by receiver operating characteristics (ROC) analysis, the NLR was divided into two groups with <2.6 and ≥2.6., Results: Elevated prechemotherapy NLR was significantly correlated with worse overall survival (OS) on univariate analysis (p=0.01). On multivariate analysis, elevated prechemotherapy NLR (HR 1.43, p=0.036) was an independent prognostic element for worse OS, but not for progression-free survival (PFS). Constantly elevated NLR or an increase in NLR after chemotherapy was correlated with poor OS, PFS and chemotherapy response. In the multivariate analysis, constantly elevated NLR was identified to be independent predictor of reduced OS and PFS., Conclusion: NLR change during chemotherapy is a better index than prechemotherapy NLR for predicting survival in patients with mCG.