Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: Review of current phase III immunotherapy clinical trials

The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer

Advance Australia fair? (in)equality, prosperity and sustainability in shaping Australia's future

Scholarships & Prizes Office. University of Sydne

CLEMASTINE, THE H1 HISTAMINE RECEPTOR ANTAGONIST, ALTERS THE HUMAN SEX AND THYROID HORMONAL PROFILES

  Objective: Clemastine is widely used as an antihistaminic drug. However, clemastine effectively acts as an antagonist of H1 histamine receptor, it has significant burden adverse effects causing common nervous system, psychiatric, and gastrointestinal ailments, as well as rare cardiac and immune system disorders. The objective of this study is to investigate whether there is a remarkable impact of clemastine administration on the human hormonal pituitary-thyroid-adrenal axis.Methods: To achieve that, hormonal profile was tested in the sera of males and females treated and untreated individuals with clemastine. This is to measure serum estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, triiodothyronine, thyroxine, fasting insulin, and cortisol levels. The circulating hormonal levels were measured quantitatively using enzyme-link immunosorbent assay.Results: We resulted that there were significant differences of the human hormonal profile on clemastine treatment.Conclusion: Hormonal profiling showed that there were remarkable signatures could be of great interest to underline some recommendations and guidelines optimizing the clemastine dosage to avoid burdens associated with the administration of this drug as well as maintain the physiological and psychological performances of both sexes exposing to clemastine during the period of allergic treatment

57. Aortic valve replacement with sutureless valve and mitral valve repair in patient with infected aortic homograft

The approach of implanting aortic sutureless valve inside the calcific homograft is suitable in redo surgery especially if associated with mitral valve surgery. Aortic valve replacement in patients who have undergone previous aortic root replacement with an aortic homograft remains a technical challenge because of homograft degeneration and the need for a redo Bentall operation. We report a case of redo aortic valve replacement (valve in valve) with a sutureless valve and mitral valve repair by miniband annuloplasty in a female patient aged 64years old who underwent aortic valve replacement with homograft 14years ago and presented by sever aortic valve regurge and sever mitral valve regurge because of infective endocarditis. This technique allows rapid aortic valve replacement in a heavily calcified aortic root. It also avoids aortic valve size affection after mitral valve repair by ordinary methods especially in patients with small aortic annulus. This technique is particularly suitable in redo procedures for homograft degeneration, it avoids performing a redo Bentall operation with its known problems as well as to avoid patient prosthesis mismatch

Pembrolizumab plus chemotherapy in advanced endometrial cancer

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P\u3c0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P\u3c0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.)

Evaluating Delay Causes for Constructing Road Projects in Saudi Arabia

In this paper, we evaluate the causes of delays in road construction projects in Saudi Arabia. The research identifies four main groups of delay causes: external factors, contractor-related factors, project management factors, and environmental factors. External factors include changes in regulations and delays in obtaining permits and approvals. Contractor-related factors include inadequate resources and poor project planning. Project management factors encompass ineffective communication and poor coordination among stakeholders. Environmental factors include adverse weather conditions and unforeseen site conditions. The study recommends measures such as improved coordination, enhanced contract management, and advanced project management techniques to mitigate these delay causes. The findings provide valuable insights for stakeholders involved in road infrastructure development in Saudi Arabia, enabling them to implement strategies for timely project delivery and improved project performance

2. Minimally invasive mitral valve surgery why do you take the risks?

During recent years, minimally invasive mitral valve surgery (MIMVS) become the preferred method of mitral valve repair and replacement in many institutions worldwide with excellent results, in spite of there is no clear difinition of minimally invasive surgery and we do not have efficient studies about the risks of MIMVS comparing to conventional mitral valve surgery. Many studies are needed to clarify the need for either conventional or minimally invasive mitral valve surgery instead of personal preference. The patient’s demographic profile, intraoperative data and postoperative outcomes of patients undergoing minimally invasive mitral valve surgery were retrospectively collected from our database from May 2011 to April 2014. We will present early and mid-term outcomes of patients undergoing minimally invasive mitral valve surgery in our institution. Seventy consecutive patients (45 male and 25 female), age 35±12 years, underwent MIMVS surgery. Mean preoperative New York Heart Association function class was 2.6±0.7. Mean ejection fraction was 50±8. Cardiopulmonary bypass was instituted through femoral cannulation (28 of 70, 40%), or direct aortic cannulation (42 of 70, 25%). Aortic cross-clamp used in (66 of 70, 94.2%). Without aortic cross-clamp in (4 of 70, 5.7%), mitral valve repair has been done in (52 of 70, 74.2%), mitral valve replacement (18 of 70, 25.7%). Concomitant procedures included AF ablation (24 of 70, 34.2%), and tricuspid valve repair (33 of 70, 47.1%). No mortality recorded, residual mitral regurge was found in (6 of 70, 8.5%) during 1 year follow up. Cardiopulmonary bypass, and “skin to skin” surgery were 95±35 and 250±74min, respectively. 4 patients (5.7%) underwent reexploration for bleeding and (57 of 70, 81.4%) did not receive any blood transfusions. Six patients (8.5%) sustained face oedema. Mean length of hospital stay was 7±3.8days. 18 patients (25.7%) did not feel any interest regarding cosmotic advantage over conventional surgery. Minimally invasive mitral valve surgery is an excellent alternative to conventional mitral valve surgery in most cases however comparing to conventional mitral surgery it shows long bypass time, long cross clamp time, difficult reexploration for bleeding and multiple body incisions

Fundamental Role of Neurochemicals Aberration in the Pathogenesis of Autism Spectrum Disorders

AIM: The aim of this research was to establish the perturbation of reliable biomarkers implicated in the pathophysiology of autism to help in the early diagnosis and to be as targets in the treatment of autism spectrum disorders (ASDs) in children and to spotlight into the complex crosstalk between these biomarkers. PATIENS AND METHODS: This study included 90 autistic children aged from 2 to 7 years old, who were classified into two groups, the atypical autism of 30 children and the childhood autism. The childhood autism group was further divided into mild-moderate autism group and severe autism group each of 30 children. The control group included 30 matched healthy children. All the participants were subjected to full psychiatric examinations, psychological investigations, and biochemical measurements, including gamma-aminobutaric acid (GABA), serotonin, dopamine (DA) in plasma, and brain-derived neurotrophic factor (BDNF) in serum. RESULTS: The autistic groups showed a highly significant increase in GABA, serotonin, DA, and BDNF levels compared to the control. Of note, the levels of GABA, DA, and BDNF were significantly increased with the increased disease severity. Furthermore, a significant positive correlation between BDNF levels and both GABA and DA levels in the childhood autism group has been recorded. CONCLUSION: The present clinical setting provides new insight into the fundamental role of BDNF in the brain of autistic children as any alterations of its level due to GABA increment cause change in serotonin and DA levels which have empirical evidence in the pathophysiology of ASD. The results received in this research, create a fertile base for the setup of particular targets in the intervention of this ailment

How does long term exposure to base stations and mobile phones affect human 3 hormone profiles?

and safety for humans continuously exposed to radio frequency 51 radiation. 52 Design and methods 53 Study subjects 54 This study was conducted for 6 years on 82 mobile phone volun-55 teers with age ranges 14-22 years (n = 41) and 25-60 years 56 (n = 41). Those users were divided into three subgroups according 57 to the time of their exposure to RFR: (weak n = 19), (moderate 58 n = 9), and (strong n = 13) per day, in addition to 20 negative control 59 subjects. 60 On the other hand, volunteers exposed to RFR emitted from base 61 stations (n = 34) were selected with age ranges 14-22 years 62 (n = 17), and 25-60 years (n = 17) and living at distances 20-100 m 63 and 100-500 m apart from the base station. Additional 10 subjects 64 of each age range living at a distance more than 500 m apart from 65 the base station were considered as negative control group