Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model

International audienceThe epithelial ovarian cancer is one of the most lethal gynecological malignancy due to its late diagnostic and many relapses observed after first line of treatment. Once diagnose, the most important prognostic factor is the completeness of cytoreductive surgery. To achieve this goal, surgeons have to pinpoint and remove nodules, especially the smallest nodules. Recent advances in fluorescence-guided surgery led us to develop a recombinant lectin as a nanoprobe for the microscopic detection of nodules in the peritoneal cavity of tumor-bearing mice. This lectin has an intrinsic specificity for a carcinoma-associated glycan biomarker, the Thomsen-Friedenreich antigen. In this study, after its labelling by a near infrared dye, we first demonstrated that this nanoprobe allowed indirect detection of nodules already implanted in the peritoneal cavity, through tumor microenvironment targeting. Secondly, in a protocol mimicking the scattering of cells during surgery, we obtained a direct and long-lasting detection of tumor cells in vivo. This lectin as already been described as a nanocontainer able to do targeted delivery of a therapeutic compound to carcinoma cells. Future developments will focus on the combination of the nanoprobe and nanocontainer aspects in an intraperitoneal nanotheranostic approach

Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials – A Systematic Literature Review

International audienceIn neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains ‘physical functioning’, ‘global improvement and satisfaction’, and ‘neuropathic pain quality’ were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment

Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial

Abstract Background Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. Methods In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130  Results At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. Conclusions In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. Trial registration ClinicalTrials.gov NCT00159159</p

Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial.

International audienceBACKGROUND: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes. METHODS: In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors' cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied. RESULTS: At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis. CONCLUSIONS: In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159159