On making ethical choices in ethnographic research into (young) people’s mediated intimacy : a research note

People's intimate life-worlds are increasingly taking place in networked media spaces such as social media, smartphone applications and virtual reality environments. For (digital) ethnographers, it becomes crucial to understand people's intense intimate attachments to mediated spaces. Many researchers are already exploring networked media spaces' affects; what opportunities they offer for people's intimacies as well as the, albeit hidden, damage they may bring. However, there are many challenges for qualitative researchers to operate ethically when inquiring into people's intimate life-worlds in networked media spaces. A framework of contextual integrity needs to consider what it means to live a personal life in deeply mediatised contexts. For an ethnographic researcher, being present in the intimate networked media spaces of research subjects, means tapping into affective networks. Responsible researchers should therefore understand the contextual affective dynamics and affordances of these networked media spaces; this implies understanding what it means to be present as a researcher and what the implications are of this presence

Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer.

The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network.info:eu-repo/semantics/publishe

Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer

Background: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. Materials and methods: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations. Results: NGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched patients. Conclusions: Our MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations.status: publishe

Targeting histone methylation to reprogram the transcriptional state that drives survival of drug-tolerant myeloid leukemia persisters

Although chemotherapy induces complete remission in the majority of acute myeloid leukemia (AML) patients, many face a relapse. This relapse is caused by survival of chemotherapy-resistant leukemia (stem) cells (measurable residual disease; MRD). Here, we demonstrate that the anthracycline doxorubicin epigenetically reprograms leukemia cells by inducing histone 3 lysine 27 (H3K27) and H3K4 tri-methylation. Within a doxorubicin-sensitive leukemia cell population, we identified a subpopulation of reversible anthracycline-tolerant cells (ATCs) with leukemic stem cell (LSC) features lacking doxorubicin-induced H3K27me3 or H3K4me3 upregulation. These ATCs have a distinct transcriptional landscape than the leukemia bulk and could be eradicated by KDM6 inhibition. In primary AML, reprogramming the transcriptional state by targeting KDM6 reduced MRD load and survival of LSCs residing within MRD, and enhanced chemotherapy response in vivo. Our results reveal plasticity of anthracycline resistance in AML cells and highlight the potential of transcriptional reprogramming by epigenetic-based therapeutics to target chemotherapy-resistant AML cells

Implementation of an Enhanced Recovery after Surgery Protocol in Advanced and Recurrent Rectal Cancer Patients after beyond Total Mesorectal Excision Surgery: A Feasibility Study

Introduction: The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. Methods: Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. Results: Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0–14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8–15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p 70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery