A new mathematical model for the interpretation of translational research evaluating six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon

Adjuvant therapy of stage IIB/III melanoma with interferon reduces relapse and mortality by up to 33% but is accompanied by toxicity-related complications. Polymorphisms of the CTLA-4 gene associated with autoimmune diseases could help in identifying interferon treatment benefits. We previously genotyped 286 melanoma patients and 288 healthy (unrelated) individuals for six CTLA-4 polymorphisms (SNP). Previous analyses found no significant differences between the distributions of CTLA-4 polymorphisms in the melanoma population vs. controls, no significant difference in relapse free and overall survivals among patients and no correlation between autoimmunity and specific alleles. We report new analysis of these CTLA-4 genetic profiles, using Network Phenotyping Strategy (NPS). It is graph-theory based method, analyzing the SNP patterns. Application of NPS on CTLA-4 polymorphism captures allele relationship pattern for every patient into 6-partite mathematical graph P. Graphs P are combined into weighted 6-partite graph S, which subsequently decomposed into reference relationship profiles (RRP). Finally, every individual CTLA-4 genotype pattern is characterized by the graph distances of P from eight identified RRP's. RRP's are subgraphs of S, collecting equally frequent binary allele co-occurrences in all studied loci. If S topology represents the genetic "dominant model", the RRP's and their characteristic frequencies are identical to expectation-maximization derived haplotypes and maximal likelihood estimates of their frequencies. The graphrepresentation allows showing that patient CTLA-4 haplotypes are uniquely different from the controls by absence of specific SNP combinations. New function-related insight is derived when the 6-partite graph reflects allelic state of CTLA-4. We found that we can use differences between individual P and specific RRPs to identify patient subpopulations with clearly different polymorphic patterns relatively to controls as well as to identify patients with significantly different survival. © 2014 Pancoska et al

Good practice recommendations on add-ons in reproductive medicine

STUDY QUESTION: Which add-ons are safe and effective to be used in ART treatment? SUMMARY ANSWER: Forty-two recommendations were formulated on the use of add-ons in the diagnosis of fertility problems, the IVF laboratory and clinical management of IVF treatment. WHAT IS KNOWN ALREADY: The innovative nature of ART combined with the extremely high motivation of the patients has opened the door to the wide application of what has become known as 'add-ons' in reproductive medicine. These supplementary options are available to patients in addition to standard fertility procedures, typically incurring an additional cost. A diverse array of supplementary options is made available, encompassing tests, drugs, equipment, complementary or alternative therapies, laboratory procedures, and surgical interventions. These options share the common aim of stating to enhance pregnancy or live birth rates, mitigate the risk of miscarriage, or expedite the time to achieving pregnancy. STUDY DESIGN, SIZE, DURATION: ESHRE aimed to develop clinically relevant and evidence-based recommendations focusing on the safety and efficacy of add-ons currently used in fertility procedures in order to improve the quality of care for patients with infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: ESHRE appointed a European multidisciplinary working group consisting of practising clinicians, embryologists, and researchers who have demonstrated leadership and expertise in the care and research of infertility. Patient representatives were included in the working group. To ensure that the guidelines are evidence-based, the literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, recommendations were based on the professional experience and consensus of the working group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 46 independent international reviewers. A total of 272 comments were received and incorporated where relevant. MAIN RESULTS AND THE ROLE OF CHANCE: The multidisciplinary working group formulated 42 recommendations in three sections; diagnosis and diagnostic tests, laboratory tests and interventions, and clinical management. LIMITATIONS, REASONS FOR CAUTION: Of the 42 recommendations, none could be based on high-quality evidence and only four could be based on moderate-quality evidence, implicating that 95% of the recommendations are supported only by low-quality randomized controlled trials, observational data, professional experience, or consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines offer valuable direction for healthcare professionals who are responsible for the care of patients undergoing ART treatment for infertility. Their purpose is to promote safe and effective ART treatment, enabling patients to make informed decisions based on realistic expectations. The guidelines aim to ensure that patients are fully informed about the various treatment options available to them and the likelihood of any additional treatment or test to improve the chance of achieving a live birth. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from ESHRE funds. There was no external funding of the development process or manuscript production. K.L. reports speakers fees from Merck and was part of a research study by Vitrolife (unpaid). T.E. reports consulting fees from Gynemed, speakers fees from Gynemed and is part of the scientific advisory board of Hamilton Thorne. N.P.P. reports grants from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare, speakers fees from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare. S.R.H. declares being managing director of Fertility Europe, a not-for-profit organization receiving financial support from ESHRE. I.S. is a scientific advisor for and has stock options from Alife Health, is co-founder of IVFvision LTD (unpaid) and received speakers' fee from the 2023 ART Young Leader Prestige workshop in China. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals and Merck A/S, consulting fees from Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos and Merck A/S, speakers fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, Theramex and Organon, travel fees from Gedeon Richter. The other authors disclosed no conflicts of interest. DISCLAIMER: This Good Practice Recommendations (GPRs) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation.ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or bedeemedinclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results.Theydo not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type.Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE

“Emotional Exhaustion and Perceived Corporate Social Responsibility: A Case Study of a Port Logistics Organization”

In an era of economic crisis, and at the shadow of major ethical scandals in organizations, Corporate Social Responsibility (CSR) strategy has emerged as a crucial element to reestablish the bond between corporations and all other stakeholders such as the local community, society and labor force. Crisis makes employees more stressful, since they work on unwarranted jobs causing them emotional exhaustion. This study aims to examine the association between employee emotional exhaustion and perceived corporate social responsibility (CSR). For this purpose, this study conducted a survey which examines if CSR (ethical, social, environmental dimensions) is negatively related to emotional exhaustion of employees on a sample of 93 employees of a port logistics management services organization. A structured questionnaire was developed in order to measure emotional exhaustion and employee perceptions about CSR activities. Building on the claim that employee perceptions of CSR activities may significantly related to emotional state, this paper examines three CSR dimensions (social, ethical and environmental) and emotional exhaustion. The results of this study indicate that environmental CSR exerts a negative significant effect on Emotional exhaustion. These finding will be of great value as they can contribute on understanding the impact of environmental CSR on emotional exhaustion with detrimental effects on employees’ productivity, job performance, and creativity. The importance of CSR environmental aspects and the relative strategies guiding CSR impact on emotional exhaustion affecting job-related outcomes are also discussed

Liver biopsy-based validation, confirmation and comparison of the diagnostic performance of established and novel non-invasive non-alcoholic fatty liver disease indexes:Results from a large multi-center study

Background: Non-invasive tools (NIT) for non-alcoholic fatty liver disease (NAFLD) screening or diagnosis need to be thoroughly validated using liver biopsies.Purpose: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT).Methods: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven NAFLD (n = 374, including 237 patients with non-alcoholic steatohepatitis (NASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of NAFLD vs. Controls, NASH vs. NAFL, histological features of NASH, and fibrosis stages.Results: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of NAFLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of NASH, no NIT demonstrated adequate performance, while in the case of specific features of NASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0–2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2–4 vs. F0–1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3–4) and mild or moderate fibrosis (F0–2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2–4 vs. F0–1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results.Conclusions: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic

Successful treatment of recurrent small bowel adenocarcinoma by cytoreductive surgery and chemotherapy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Small bowel adenocarcinoma is a rare malignancy associated with a poor prognosis and there is little evidence of effective treatment. Recurrent small bowel adenocarcinoma is an intractable disease for which there is little information available regarding its treatment by palliative therapy. We present a case of recurrent small bowel adenocarcinoma successfully treated by cytoreductive surgery and palliative chemotherapy.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Japanese female who developed a peritoneal metastasis from recurrent small bowel adenocarcinoma after curative resection and adjuvant chemotherapy with S-1 and polysaccharide K. She underwent cytoreductive surgery followed by chemotherapy with folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K. Subsequently, no sign of a recurrence was observed 42 months after the second operation.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of the successful treatment of peritoneal metastasis from small bowel adenocarcinoma by cytoreductive surgery and combination chemotherapy (folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K).</p