The prognostic role of polypharmacy in metastatic colorectal cancer patients treated with regorafenib.

Aim: To evaluate polypharmacy (PP) in patients with metastatic colorectal cancer receiving regorafenib. Methods: Patients with metastatic colorectal cancer receiving regorafenib were included and divided into two categories by their PP status: PP- (<5 regular drug use/day) and PP+ (≥5 regular drug use/day). Results: 80 patients were included. 31 (38.7%) patients had PP. The median number of drugs used was three and seven in PP- and PP+ patients, respectively. Antiemetics (26.5%) and antacids (48.4%) were the most common drugs used by PP- and PP+ patients, respectively. In multivariate analysis, the risk of death was higher in PP+ patients (hazard ratio: 2.1; 95% CI: 1.2-3.7; p = 0.005). Conclusion: PP was an independent prognostic factor for overall survival in patients with metastatic colorectal cancer receiving regorafenib.

Regorafenib is a targeted therapy option that is used in patients with chemotherapy-refractory metastatic colorectal cancer. Because of the chemotherapy-refractory stage of the disease, patients are prone to use more medications for symptom palliation. Polypharmacy (PP) refers to the drug burden in an individual, and the use of five or more drugs in a day is usually considered to represent PP. In this study, the authors assessed the impact of PP in patients with metastatic colorectal cancer treated with regorafenib. The authors' study found that PP had a negative impact on survival outcomes in these patients. This is why inappropriate drug use should be assessed at each visit and the medication discontinued if it is not an essential part of the treatment.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Evaluation of the effect of shift working and sleep quality on semen parameters in men attending infertility clinic.

We aimed to evaluate the effect of shift work on semen parameters together with the effect of sleep quality in men attending infertility clinic. The participants were divided into two groups as follows: 104 shift worker men (Group 1) and 116 nonshift worker men (Group 2). Groups were compared in terms of semen parameters, Depression Anxiety Stress Scale-21 (DASS-21), and Pittsburg Sleep Quality Index (PSQI) scores. A higher rate of oligozoospermia and poor sleep quality and a lower mean normal morphology percentage was observed in shift workers than nonshift workers (p = .006, .039 and .036 respectively). In addition, a positive correlation was seen between sleep duration and sperm concentration, while a negative correlation was found between sleep latency and total sperm count. Shift working together with high PSQI score was also a significant association with oligozoospermia when controlling for the other variables of age, total testosterone, DASS-21 stress score, smoking and varicocele (OR = 2.11, 95% CI 1.03-4.34 and OR = 1.18, 95% CI 1.01-1.39 respectively). In this study, infertile shift workers had a lower percentage of normal morphology and higher rates of oligozoospermia and poor sleep quality. Considering that shift workers have lower sleep quality, it seems that shift working negatively affects the circadian rhythm.

Relationship between the G protein-coupled oestrogen receptor and spermatogenesis, and its correlation with male infertility.

The aim of this study was to investigate the diagnostic value of serum G protein-coupled oestrogen receptor (GPER) levels and their correlation with semen parameters in men with infertility. The participants were divided into two groups as follows: 76 fertile control men (Group 1) and 77 infertile men (Group 2). Semen analysis, hormonal evaluation, serum GPER level and scrotal ultrasound of the participants were evaluated. Follicle-stimulating hormone and total testosterone levels were not significantly different between the groups (p = .413 and p = .535 respectively). The oestradiol level in Group 1 was significantly lower than that in Group 2 (p < .001). The serum GPER level was found to be significantly higher in Group 1 than that of Group 2 (p < .001). GPER levels were positively correlated with the total sperm count, sperm concentration, motility and morphology in Group 2 (r = 0.303, 0.345, 0.260 and 0.322, respectively, p < .001). In this study, GPER levels were positively correlated with sperm parameters, and it was hypothesised that the decrease in GPER expression might be associated with male infertility by adversely affecting spermatogenesis.

The association between chronic spontaneous urticaria and HLA class I and class II antigen

Background/aim: Chronic spontaneous urticaria (CSU) is a chronic disease with an unknown etiology. In human leukocyte antigen (HLA) system, the association of class I and class II antigens with autoimmune diseases has been identified and HLA antigens that have a tendency to or can prevent chronic urticaria have been studied. The aim of this study is to investigate the association between chronic spontaneous urticaria and HLA class I and class II antigens. Materials and methods: A total of 80 subjects, 40 patients with CSU and 40 healthy individuals were enrolled in the study. DNA sample isolation from blood was primarily done by the real-time polymerase chain reaction (RT-PCR) technique for the first time. Using HLA SSP Typing Kit (ROSE Cat. No: 800118) PCR technique, HLA-A, B, C, DRB and DQB alleles from DNA samples were analyzed. Results: The mean age was 36.80 ± 9.48 years and the duration of the disease was 4.26 ± 5.18 years. Among the HLA class I and class II antigens, HLA-A was detected significantly more often in the control group (P = 0.039). HLA-DRB1 was more often detected in the CSU group but no statistical difference (P > 0.05). Conclusion: It can be considered that HLA-DRB1 may have a tendency to CSU, while HLA-A might prevent the disease.

The E3 ubiquitin ligase RNF121 is a positive regulator of NF-κB activation.

BACKGROUND: The nuclear factor κB (NF-κB) family members regulate several biological processes as cell proliferation and differentiation, inflammation, immunity and tumor progression. Ubiquitination plays a key role in NF-κB activation and the ubiquitylated transmitters of the NF-κB signaling cascade accumulate in close proximity to endomembranes. FINDINGS: We performed an unbiased siRNA library screen targeting the 46 E3 ubiquitin ligases bearing transmembrane domains to uncover new modulators of NF-κB activation, using tumor necrosis factor-α (TNF-α) receptor (TNFR) stimulation as a model. We report here the identification of a new Golgi Apparatus-resident protein, RNF121, as an enhancer of NF-κB promoter activity through the catalytic function of its RING domain. From a molecular standpoint, while knocking down RNF121 did not alter RIP1 ubiquitination and IKK activation, the proteasomal degradation of IκBα was impaired suggesting that this E3 ubiquitin ligase regulates this process. However, RNF121 did not directly ubiquitinate IκBα While they were found in the same complex. Finally, we discovered that RNF121 acts as a broad regulator of NF-κB signaling since its silencing also dampens NF-κB activation following stimulation of Toll-Like Receptors (TLRs), Nod-Like Receptors (NLRs), RIG-I-Like Receptors (RLRs) or after DNA damages. CONCLUSIONS: These results unveil an unexpected role of Golgi Apparatus and reveal RNF121 as a new player involved in the signaling leading to NF-κB activation.

Evening type negatively affects semen quality by deteriorating sperm morphology: Results from an infertility clinic.

OBJECTIVE: The effect of sleep-related variables on the reproductive system has garnered attention in recent years. One of the mediators that reportedly plays an important role in the relationship between sleep disorders and the reproductive system is a disruption of the circadian rhythm. The aim of curent study is to investigate the effect of chronotype on morning semen quality. STUDY DESIGN: Three-hundred and fourteen patients who applied to the infertility clinic were included in the study. The patients filled a socio-demographic data form. The "Pittsburg Sleep Quality Index (PSQI) was used to evaluate the sleep quality while the chronotypes of the patients were evaluated with the "Morningness -Eveningness-Questionnaire (MEQ)". Semen analyses and biochemical analysis for testosterone serum plasma level of all patients were performed. RESULTS: Twenty-one patients were assigned as evening, 187 patients were assigned as intermediate, and 106 were assigned as morning chronotype. No statistically significant difference was identified in the comparison of the mean MEQ scores between patients with low and normal sperm concentrations(p = 0.884). A correlation analysis indicated the presence of a significant positive correlation between normal morphology and MEQ scores (r = 0.13, p < 0.05) and a negative corelation between the hours spent in bed and sperm concentration (r = -0.13, p < 0.05). A general linear model created with independent variables suggested that the presence of varicocele and MEQ scores had a significant effect on normal morphology. CONCLUSION: The results of present study support that evening type could negatively affect sperm morphology; additionally, the time spent in bed also negatively affected sperm concentration.

At What Age Threshold does the Decline in Semen Parameters Begin?

OBJECTIVE:  To analyse changes in semen parameters according to different age groups in men presenting to an infertility clinic, and determine the age threshold for decline in semen quality. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Andrology Laboratory, Department of Urology, Kahramanmaras Sütçü Imam University, Turkey, from January 2018 to December 2019. METHODOLOGY: Semen analysis records of infertile men, who were referred to Andrology Laboratory, were retrospectively evaluated. The age groups were categorised as 20-29, 30-34, 35-39, 40-44, and 45-55 years. Each group was completed to 100 semen samples retrospectively and sequentially without any preferences. The differences of semen parameters between age groups were analysed with the one-way ANOVA test. Linear relationship was checked by ANOVA. RESULTS: The mean age of 500 patients was 37.18 ± 8.11 years. While no linear relationship was observed in semen volume, concentration, and total sperm count with age (p=0.133, p=0.290 and p=0.261, respectively). A linear decline was observed in progressive motility, vitality, and morphology parameters with advancing age (all, p<0.001). In linear contrast analysis according to the 20-29 age group; significant decline in progressive sperm motility, morphology, and vitality started and continued in the 35-39 age group (all, p<0.001). CONCLUSION: With advancing age, a significant linear decrease in sperm motility, morphology and vitality was observed in infertile men. This significant decline in sperm motility, morphology and vitality continues at age 35 and over. Therefore, infertile men who plan to postpone paternity should consider the age factor. Key Words: Aging, infertility, Paternal age, Semen analysis, Sperm.