Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines.

BACKGROUND: Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood. METHODS: This work was conducted to analyze the implication of Rac3 in the aggressiveness of two breast cancer cell lines, MDA-MB-231 and MCF-7: both express Rac3, but MDA-MB-231 expresses more activated RhoA. The effect of Rac3 in cancer cells was also compared with its effect on the non-tumorigenic mammary epithelial cells MCF-10A. We analyzed the consequences of Rac3 depletion by anti-Rac3 siRNA. RESULTS: Firstly, we analyzed the effects of Rac3 depletion on the breast cancer cells' aggressiveness. In the invasive MDA-MB-231 cells, Rac3 inhibition caused a marked reduction of both invasion (40%) and cell adhesion to collagen (84%), accompanied by an increase in TNF-induced apoptosis (72%). This indicates that Rac3 is involved in the cancer cells' aggressiveness. Secondly, we investigated the effects of Rac3 inhibition on the expression and activation of related signaling molecules, including NF-κB and ERK. Cytokine secretion profiles were also analyzed. In the non-invasive MCF-7 line; Rac3 did not influence any of the parameters of aggressiveness. CONCLUSIONS: This discrepancy between the effects of Rac3 knockdown in the two cell lines could be explained as follows: in the MDA-MB-231 line, the Rac3-dependent aggressiveness of the cancer cells is due to the Rac3/ERK-2/NF-κB signaling pathway, which is responsible for MMP-9, interleukin-6, -8 and GRO secretion, as well as the resistance to TNF-induced apoptosis, whereas in the MCF-7 line, this pathway is not functional because of the low expression of NF-κB subunits in these cells. Rac3 may be a potent target for inhibiting aggressive breast cancer.

Prevalence of transthyretin amyloidosis in patients undergoing carpal tunnel surgery: a prospective cohort study and risk factor analysis.

Transthyretin amyloidosis is a frequent cause of heart failure, resulting from an accumulation of abnormal proteins in the myocardium. Recent research has highlighted the importance of early diagnosis to enhance the effectiveness of specific treatments. Extra-cardiac symptoms may precede several years before cardiac complications, with carpal tunnel syndrome often considered a red flag. The aim of this prospective, observational cohort study was to determine the incidence rate of positive synovial biopsies for transthyretin amyloidosis in patients aged 60-80 years undergoing carpal tunnel decompression, and to identify risk factors. The diagnosis of transthyretin amyloidosis was confirmed through the analysis of synovial tissue biopsies using Congo Red and immunohistochemical staining. The study included 254 patients, with an 18.5% prevalence of transthyretin amyloidosis. Risk factors for positive test results were identified as male sex, trigger finger, hearing disorders and valve disease. A predictive analysis using logistic regression yielded a probability model for individuals belonging to the positive group.Level of evidence III.

Comparison of results of arthroscopic arthrolysis between traumatic and degenerative elbow stiffness.

INTRODUCTION: Elbow stiffness significantly affects the patient's quality of life. This joint must have at least 30°/130° extension/flexion and 50°/50° pronation/supination to function normally according to Morrey. HYPOTHESIS: The objective of this study was to evaluate functional outcome of arthroscopic arthrolysis by comparing stiffness of post-traumatic and degenerative origin. The hypothesis was that this surgical technique allows functional improvement in any indication but with a faster result in degenerative pathology. MATERIAL AND METHODS: This was a retrospective study including all patients who underwent elbow arthrolysis under arthroscopy, operated on by a single operator, between 2013 and 2020. Thirty-four patients were included, with a mean age of 45years (range, 18-78years). Patients were divided into two groups according to etiology. Group A (post-traumatic) consisted of 18 patients with a mean age of 33years (range, 18-64years) and group B (degenerative) of 16 patients with a mean age of 59years (range, 42-78years). All patients were clinically assessed at a mean 27months. Range of motion, level of satisfaction and Mayo Elbow Performance Score (MEPS) were collected. RESULTS: In the overall series, preoperative range of motion was 81° and significantly improved postoperatively to 122° (p<0.001). The preoperative data of the 2 groups were comparable except for age (p<0.001) and MEPS (p=0.044). Postoperatively, range of motion improved significantly in both groups but with greater gain in group A (p=0.003). MEPS improved significantly in both groups, but the postoperative score was poorer in group B (p=0.001). Recovery of range of motion was faster in group B (2.4months) than in group A (3.7months) (p=0.021). There were 5 complications: 4 secondary decompensations of ulnar tunnel syndrome, and 1 postoperative radial nerve paresis. 94% of patients were satisfied or very satisfied with the result of surgery. CONCLUSION: Arthroscopic arthrolysis is an effective option for post-traumatic and non-traumatic elbow stiffness. Improvement was significant in terms of both function and range of motion, with, however, better results in the post-traumatic group but results achieved more rapidly in the degenerative pathology group. LEVEL OF EVIDENCE: IV, retrospective study.

Acute pain after digital crushing and nicotine intoxication. Cigarettes are always a false friend. A prospective study.

BACKGROUND: Nicotine addiction is a public health problem. Our hypothesis was that the degree of nicotine dependence is positively correlated with the perceived intensity of acute pain. MATERIALS AND METHODS: A single-center prospective comparative observational study was conducted from 2019 to 2021. Patients included presented distal phalanx extra-articular trauma of less than 24hours' progression. We compared a group of smokers with a group of non-smokers. A Digital Pain Scale (DPS) was assessed at time of trauma, at first consultation, and once a day until the fifth day post-trauma. A Fagerström test was performed. The primary endpoints were the correlation between dependence and DPS and the correlation between the amount of tobacco consumed and DPS. The secondary endpoints were analgesic consumption according to Fagerström, DPS and tobacco consumption. RESULTS: Sixty-seven patients were included: 26 smokers, 41 non-smokers. No significant correlation was found between dependence level or amount of tobacco used and DPS. Consumption of level II analgesics was significantly 2-fold higher in the smoking group on the second, third and fifth day: respectively, 2.15 tablets versus 1.22 (p=0.02), 1.27 versus 0.49 (p=0.01), and 0.69 versus 0.20 (p=0.04). CONCLUSION: Patients who smoke are exposed to more frequent and more intense pain and consume more palliative painkillers. LEVEL OF EVIDENCE: IIB; exposed vs. non-exposed cohort.

Septic arthritis of the fingers: is short-term oral antibiotic therapy appropriate?

The management of septic arthritis of the hand is poorly described and there is no consensus. It is based on how septic arthritis of the large joints is managed, despite certain specificities related to the hand, typically involving inpatient management and intravenous antibiotic therapy. The primary objective of this work was to evaluate our postoperative protocol for the management of septic arthritis of the hand with short-term antibiotic therapy. The secondary objective was to determine the risk factors for treatment failure. We conducted a retrospective, descriptive, single-center study and analyzed the medical records of patients managed for septic arthritis of the fingers over a 1-year period from January 2018 to December 2018. We collected patient demographics and all pre-, intra-, and postoperative data. A total of 128 patients were included. The median age was 52.4 years (41-66). An exogenous source of contamination was reported in 98% of cases (animal bite, plant thorn, wound, cyst trituration, etc.). The most frequently isolated microorganism was Staphylococcus aureus (45%), followed by Streptococcus spp. (22%) and Pasteurella spp. (18%). The vast majority of patients (79%) were treated with oral amoxicillin/clavulanic acid. This treatment was continued in 91% of patients after microbiological results were obtained for a median treatment duration of 8 days (7-15). Nine percent of patients failed treatment. The risk factors identified were crush wounds (p = 0.04), initial radiological abnormalities (chondrolysis and/or osteolysis) (p = 0.016) and infection with Pasteurella spp. (p = 0.015). Our study suggests that simplified antibiotic therapy is feasible for the management of septic arthritis of the hand with short duration, broad spectrum oral antibiotics in the absence of identified risk factors.

Fast-track teaching in microsurgery.

INTRODUCTION: In France, microsurgery is taught in University diploma courses, for a mean 100hours (range, 45-120hours) extending over several months. This training, spread over the year, encounters problems of maintaining high-quality supervision and enduring acquisition of skills. These difficulties risk leading to withdrawal of certain courses, already suffering from funding issues and administrative requirements for animal welfare. MATERIAL AND METHOD: We report our experience with a 2-week module comprising nine 4-hour sessions (total, 36hours), with continuous supervision of 5 students in each of 2 groups (10 students), enabling personalized learning. At the end of each session, an assessment questionnaire was filled out by teachers and students. RESULTS: Students' scores increased from a mean 23.9/30 points (range, 20 - 30) at session 3 to 26.9 points (range, 23 - 30) at session 9 (p=0.012). At the end of session 3, students were grouped as good, average or beginners, based on the first assessments: i.e., with differences in level between groups at session 3. At the end of session 9, all 3 groups showed statistically comparable levels. Comparison between student and teacher questionnaire responses showed a significant discrepancy in 7 of the 10 cases in week 1, and no significant discrepancy in 7 of the 10 cases by the end of week 2. DISCUSSION: The efficacy of condensed learning is based on immediate repetition of exercises, following Ebbinghaus: without repetition, memory decays exponentially, whereas if the information is rapidly repeated, the curve flattens and memory is consolidated. The present rapid improvement in the acquisition of the principles of microsurgery stimulated the enthusiasm of both students and teachers for what is reputed to be a demanding type of training. The study showed that acquisition, assessed in terms of vascular suture reliability, was achieved by the end of a 36-hour module, regardless of the student's baseline level.

Direct effect of bevacizumab on glioblastoma cell lines in vitro.

Bevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells.