Explore the vast range of titles available.

Stem cell transplantation is a highly stressful treatment for hematological cancer patients, negatively impacting their quality of life. Hypnosis has proven effective in managing symptoms like pain, fatigue, and anxiety, and improving quality of life. Virtual reality (VR) is used in cancer treatments to distract from pain, and combining VR with hypnosis (VRH) could enhance the hypnotic experience. However, methodological limitations in current studies prevent clear evaluation of its effectiveness, particularly for individualized care and psychosocial interventions. 1) To evaluate the preliminary effects of VRH in reducing anxiety, pain, and fatigue during stem cell transplant, improving quality of life post-intervention. 2) To assess intervention feasibility, including patients' experiences, satisfaction levels, and recommendations for improving the VRH tool. This study will involve 60 hematology patients divided into two groups: VRH and waiting list. Anxiodepressive symptoms, pain, quality of life, fatigue, absorption, dissociation, and amusement will be assessed before, immediately after the intervention, and at one- and three-month follow-ups using validated psychological scales and numeric rating scales (0-10). Semi-structured interviews will capture patient expectations, satisfaction, and feedback. Data will be analyzed using MANOVA (or non-parametric alternatives) and thematic analysis. The study's primary goal is to assess VRH's effectiveness compared to standard care in a feasibility randomized controlled trial (RCT). It will also provide data for improving the VRH tool (version 2.0) and assess its usability. In the long term, findings will help integrate VRH into oncology clinics, offering an innovative intervention to support patients throughout treatment. ClinicalTrials.gov NCT06817759.

The Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL-guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL-guided fentanyl administration would reduce intra-operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes. University hospital, operating room. 70 adult patients, ASA 1–3, scheduled for total laparoscopic hysterectomy. Patients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group. Fentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post-anesthesia care unit and up to 24 h. Sixty-six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL-guided group compared to the SOC group: 81 (24) vs 108 (66) μg.h−1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post-anesthesia care unit and at 24 h were not significantly different between the two groups. NOL-guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL-guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post-anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed. •NOL index is a recently developped index to better assess intraoperative nociception level•NOL-guided intraoperative antinociception allows for rationalized and personalized management of opioids•In hysterectomies it resulted in a significant reduction of intraoperative doses of fentanyl per hour of surgery•No significant difference was seen on postoperative pain scores and analgesics' consumption•Larger studies must be proposed in the future, powered on these postoperative outcomes.

Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. A prospective randomized monocentric trial. Perioperative care. 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties. •Propofol and sevoflurane's intrinsic antinociceptive properties are not yet clear.•Objective measurement of intraoperative nociception using the multiparametric NOL index helps precisely evaluate noxious stimulations.•Propofol and sevoflurane intraoperative antinociceptive properties were found to be similar.•No difference was observed in postoperative pain scores and consumption of analgesics.

Background Residual neuromuscular blockade (rNMB) after surgery can lead to complications such as respiratory distress, increased length of hospital stay, and higher healthcare costs. Sugammadex, a selective relaxant-binding agent, has shown efficacy in reversing rocuronium-induced neuromuscular blockade more rapidly than neostigmine. This study aimed to evaluate the effectiveness of a low dose of sugammadex (0.5 mg.kg −1 ) compared to standard neostigmine with glycopyrrolate for the reversal of moderate rocuronium-induced neuromuscular blockade. Methods This randomized, double-blind, controlled trial included adult patients undergoing surgery with rocuronium-induced moderate neuromuscular blockade. Participants were randomized to receive either low-dose sugammadex or standard-dose neostigmine with glycopyrrolate at the end of surgery. The primary outcome was the time to achieve a Train-of-Four (TOF) ratio of ≥ 0.9 after administration of the reversal agent. Secondary outcomes included extubation time, incidence of sugammadex rescue therapy for incomplete reversal, and postoperative complications. Statistical analysis used t-tests and Mann–Whitney-Wilcoxon tests for continuous variables and chi-square tests for categorical variables, with significance set at p  < 0.05. Results The median time to reach TOF ratio of ≥ 0.9 was significantly shorter in the sugammadex group (4.3 min, IQR: 3.2–6) compared to the neostigmine group (20.6 min, IQR: 10.1–21.3, p  < 0.001). Extubation times were also reduced with sugammadex, with a median of 11.6 (IQR: 8.6–15.1) minutes versus 25.9 (IQR: 17.7–29.7) minutes in the neostigmine group ( p  < 0.001). Only 4.8% of patients in the sugammadex group required rescue therapy to reverse the neuromuscular block with TOF ratio of ≥ 0.9, compared to 60.6% in the neostigmine group ( p  < 0.001). No significant differences were observed in postoperative respiratory complications or PACU length of stay. Conclusions Low-dose sugammadex provides a faster and more reliable reversal of moderate neuromuscular blockade than standard-dose neostigmine, with implications for improved operating room efficiency and patient safety. Continuous neuromuscular monitoring remains essential, as a small proportion of patients may still require additional intervention. Trial registration Registered retrospectively at ClinicalTrials.gov with registration number NCT05718934 on 2023–02-08.

The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOXB9 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-ss, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.

Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.

Multiple myeloma (MM) and stem cell transplantation (SCT) significantly impact patients’ quality of life. Virtual reality with hypnosis (VRH) has emerged as a promising nonpharmacological intervention to address these challenges, yet data on its acceptability and user experience remain scarce. This study assessed the acceptability and user experience of a VRH intervention among adult patients with MM who had undergone allogeneic SCT. Participants used a VRH application and rated their experience through standardized questionnaires and semistructured interviews. Quantitative data were analyzed descriptively, and qualitative data underwent descriptive content analysis. Findings indicated high patients’ satisfaction, strong perceived relevance, and low cybersickness. Qualitative analysis revealed perceived emotional and psychological benefits. VRH was deemed particularly suitable during hospitalization and treatment periods. This study shows the potential of combining virtual reality and hypnosis for MM patients following SCT. Indeed, they showed high satisfaction levels, paving the way for further studies evaluating the clinical efficacy of such interventions.

We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator of p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function of p53. However, the detailed mechanism remains unknown. Here we show that ASPP2 is a novel substrate of mitogen-activated protein kinase (MAPK). Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes. In contrast, an ASPP2 phosphorylation mutant exhibits reduced p53 binding and fails to enhance transactivation and apoptosis. Thus phosphorylation of ASPP2 by RAS/MAPK pathway provides a novel link between RAS and p53 in regulating apoptosis.

Background Although intravenous dexamethasone prolongs the analgesic duration of interscalene brachial plexus block, it is uncertain whether this effect can be observed using lower doses of dexamethasone. This study evaluated the impact of intravenous dexamethasone (4 mg and 10 mg) on the analgesic duration of single-shot interscalene block after arthroscopic shoulder surgery. We hypothesized that both doses would prolong the analgesic duration compared with placebo. Methods This was a prospective double-blind randomized placebo-controlled study in patients undergoing elective arthroscopic shoulder surgery under regional anesthesia with a single-shot interscalene block (0.5% ropivacaine 20 mL). Patients received dexamethasone 4 mg (D4), dexamethasone 10 mg (D10), or a placebo (normal saline [NS]) intravenously at the time of block completion. The primary outcome was the duration of analgesia, defined as the time from the onset of sensory blockade to the first analgesic request. The primary outcome was first analyzed with a Kruskal-Wallis test and then with a Mann-Whitney test for pairwise between-group comparison. Results Sixty-nine patients completed the study. The median [interquartile range] duration of analgesia was significantly different between the three groups (D4, 19.7 [16.9-23.3] hr; D10, 19.1 [11.5-22.8] hr; and NS, 11.8 [9.3-14.0] hr; P = 0.001). This difference was statistically significant for D4 and D10 compared with placebo (median difference [MD], 7.8 hr; 95% confidence interval [CI], 4.6 to 11.1 hr; P < 0.001; and MD, 7.4 hr; 95% CI, 4.2 to 10.5 hr; P = 0.001, respectively) but not for D4 compared with D10 (MD, 0.5 hr; 95% CI, −2.8 to 3.7 hr; P = 0.38). Conclusions Low doses of intravenous dexamethasone (4 mg and 10 mg) significantly prolong the analgesic duration of interscalene block. This trial was registered at ClinicalTrials.gov (NCT02412657).

The nociception level index (NOL) is a multi-parameter index that incorporates changes in autonomic parameters to evaluate nociception, with more painful stimuli causing more pronounced index variations. How this nociception monitor relates to the pain experience is uncertain, and patients with chronic pain may respond differently to acute pain due to alterations in pain processing. The goal of this pilot study was to evaluate NOL index variations after a painful physiotherapy exercise in patients with upper limb complex regional pain syndrome. Baseline NOL indexes were recorded using a finger probe (PMD-200™ Monitor, Medasense, Israel) and patient reported baseline pain scores using an 11-point numeric rating scale (NRS). Patients then performed a painful physiotherapy exercise and NOL index and pain scores were again recorded. The same procedure and recordings were repeated after a stellate ganglion block. Data were analyzed using a paired Student T test and a P value < 0.05 was considered statistically significant. Twenty patients (12/20 female, 10/20 right-sided) were included in this study. Patients reported moderate baseline pain (4.0 ± 2.7) despite having a low baseline NOL index (7.66 ± 5.76 out of 100). NRS and NOL index scores increased significantly during exercise, both before and after the block. The NOL index increased significantly when patients reported increased pain, indicating that it could eventually be useful in the objective assessment of acute pain in the chronic pain patients. However, NOL index was not able to reflect pain levels at rest, before the painful stimulation, in this chronic pain population. Further studies are needed to better assess NOL index utility at rest and to confirm these findings in this specific chronic pain population.