Therapeutic Impasse Research Articles

Clinical Recommendations for Addressing Impasses in Long-Term Psychotherapy

Many clients benefit from psychotherapy sessions that extend across months or years. However, there is a risk for therapeutic impasse in long-term psychotherapy in which the work can become repetitive or with limited gains over time. The current paper provides five transtheoretical principles to increase the impetus in long-term therapy. The five principles include: planful spontaneity, habitual creativity, pushing the limits of the therapeutic alliance, guided discovery, and specific broad goals. The therapist is encouraged to share responsibility for creative flexibility with the client in each session, including within the therapeutic alliance and the real relationship. The therapist can use a series of questions to promote a process of guided discovery. A clear focus on principles of psychology and goals that reflect maintenance of gains, development of strengths, and promotion of enrichment can ensure that the therapy continues to produce change over the length of the relationship.

AML-332 Antibiotic Resistance Profile of Blood Culture Isolates in Neutropenics in Morocco

The emergence of bacterial resistance to antibiotics is an international health issue affecting all age groups and all clinical profiles. These multidrug-resistances lead to therapeutic impasses and pose a problem of therapeutic management, particularly in immunocompromised patients. The aim of our study is to highlight the different germs isolated in blood culture as well as their antibiotic resistance profiles in patients hospitalized on the protected side of our department. This is a prospective study lasting 6 months, from June 2021 to December 2021, carried out within the protected side of the hematology department, in 53 patients who presented an episode of febrile neutropenia and in whom a standard blood culture was performed. Of the blood cultures performed in our 53 patients, 31 (58%) blood cultures were positive, with demonstration of a bacterial infection in 20 patients, i.e., 65% of cases. The main bacterial species found are Klebsiella pneumonia in 3 cases (15%), Acinetobacter baumannii in 3 cases (15%), Escherichia coli in 4 cases (20%), and Pseudomonas aeruginosa in 2 cases (10%). Out of this total of 20 isolated germs, there were 13 infections by multidrug-resistant bacteria (MRB), i.e., 65% of the cases of bacterial infection in our sample. The incidence of MRB is 0.44 cases per 59 patients per year. The antibiogram of the main MRB isolated shows the emergence of increased resistance to the antibiotics used: Klebsiella pneumonia is resistant to penicillins A, fluoroquinolones, C2G, C3G, and gentamycin; ABRI is resistant to aminoglycosides, cephalosporins, fluroquinolones, piperacillin-tazobactam, and imipenem; PARI is resistant to piperacillin-tazobactam, ticarcillin ceftazidime, fluoroquinolones, aminoglycosides, and carbapenem; and Escherichia coli is resistant to ampicillin, amoxicillin, cefoxitin, ceftriaxone, ceftazidime, ciprofloxacin, gentamicin, and ertapenem. The acquisition of resistance to antibiotics complicates therapeutic management and exposes patients to a high risk of death from septic shock, hence the importance of prevention through strict hygiene measures, staff awareness of patient health, and the rationalization of the prescription of antibiotic therapy, as well as the implementation of a monitoring system for multidrug-resistant bacteria.

Pre-hospital Consumption of Antibiotics in Children Admitted to the Pediatric Ward of CHU Tambohobe Fianarantsoa

Introduction: Antibiotic consumption is on the rise; this increases the risk of bacterial resistance which represents a public health threat with an increasing number of therapeutic impasses. The objective of our study is to evaluate the pre-hospital consumption of antibiotics in children admitted to the pediatric service of CHU-Tambohobe Fianarantsoa. Method: This is a prospective cross-sectional study during a period of 6 months in the pediatric department of the CHU-Tambohobe Fianarantsoa; including all children admitted with antibiotics before their hospitalization. Results: We included 105 cases, i.e. 27.5% of hospitalized patients. The age of our patients ranged from 0 to 180 months with a median age of 24 months. The infectious sites for which antibiotics were prescribed were predominantly respiratory [27.6%] and ENT [24.5%]. Self-medication was used in 11.4% of cases, and 88.6% had consulted a health centre, 76% of whose prescribers were doctors. The antibiotic used was not adapted to the infection site in 54.3% of cases, and the dose was insufficient in 48.27%. The most prescribed antibiotic was Amoxicillin in 37.9% of cases, followed by Cotrimoxazole in 15.9%. The evolution was marked by the absence of improvement which motivated the hospitalization of the child. Conclusion: Our study showed an inappropriate pre-hospital consumption of antibiotics. Continuous training on the correct prescription of antibiotics as well as the implementation of antibiotic therapy protocols are necessary.

Treatments for Non-Syndromic Inherited Ichthyosis, Including Emergent Pathogenesis-Related Therapy.

The term 'inherited ichthyosis' refers to a heterogeneous group of mendelian disorders of cornification that involve the integument with varying degrees of scaling. The management of ichthyosis poses a challenge for most physicians. Treatment options proposed in the literature include moisturizers, topical keratolytics, topical and systemic vitamin D analogues, and topical and systemic retinoids; however, some of these modalities are less reliable than others. Despite the therapeutic impasse imposed by the options above, the emergence of pathogenesis-based treatments along with novel gene therapies appear promising and hold the potential to halt or even revert disorders that arise from single genetic mutations, although research is still quite lacking in this domain. Hence, this review aims to highlight the various treatment modalities available for the management of the cutaneous manifestations of non-syndromic inherited ichthyosis, with an added emphasis on pathogenesis-targeted therapies.

Epidemiology and Sensitivity to Antibiotics of Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases (ESBL) in the Region of Nouakchott (Mauritania)

Introduction: Extended-spectrum beta-lactamases (ESBL) are a large heterogeneous family of bacterial enzymes discovered in 1980. They are induced either by plasmids or by mutation of the natural genome in the bacterium. Both mechanisms give affected bacteria the ability to hydrolyze a very wide variety of beta-lactams. (ESBL)-producing bacteria represent a major concern due to their epidemic spread and their multiresistance to antibiotics The purpose of this study was to: determine their frequency of ESBL, know their distribution according to sex, hospital department, assess their levels of resistance to antibiotics and educate clinicians on the rational prescription of antibiotics. Materials and Methods: This is a retrospective study which was carried out within the central laboratory of the National Hospital Center of Nouakchott (CHN) over two years. The antibiogram was carried out by the method of diffusion in agar medium or on the Vitek-2 automaton (Biomérieux®) The production of ESBLs has been demonstrated by looking for a synergy between clavulanic acid and third-generation cephalosporins according to the usual techniques. Results: Out of 650 species of Enterobacteriaceae, 18.46% produced ESBL, including 58% in hospitalized patients and 42% in outpatients. The ESBL resistance rate was high to quinolones, aminoglycosides (except amikacin) and cotrimoxazole, fosfomycin and carbapenems retain good activity. Discussion: ESBLs are increasingly incriminated in both community-acquired and nosocomial infections and represent a real public health problem. In fact, 42% of ESBL isolated during our study came from outpatient consultations. This dissemination of ESBL in the community is alarming and could be explained, in part, by the anarchic use of antibiotics, it has also been mentioned by several studies. Fosfomycin retains excellent efficacy against ESBL in our study with 90% sensitivity. The resistance of Enterobacteriaceae to carbapenems remained marginal with sensitivity rates of 98 to 100% , making them the best treatment against ESBL-producing Enterobacteriaceae. However, the misuse of these molecules has led to the emergence of resistance to these antibiotics, especially in certain enterobacteriaceae. Conclusion: Considering the results of our study and the data from the literature, it clearly appears that ESBLs are taking an increasingly important place among multiresistant bacteria. The increase in resistance should be compared with the increase in antibiotic consumption. These trends are problematic because they promote not only the emergence and spread of ESBL enterobacteriaceae, but also those of carbapenemase-producing enterobacteriaceae (CPE). Faced with this worrying situation and given the increased risk of therapeutic impasse caused by these multi-resistant strains; very early detection of ESBL germ infections, isolation of patients carrying a transmissible infection and rational use of antibiotics should be carried out.

Misdiagnosis and therapeutic impasse in psychiatry

IntroductionWe frequently receive patients with atypical psychiatric symptoms admitted in our department after consulting other psychiatrists and triying several treatments.ObjectivesTo highlight the factors of misdiagnosis in patients of our department.MethodsWe recruited 70 patients during their appointment or during their hospital admission in our department between March and April 2021. We collected the patients’ socio-demographic and clinical data using a pre-designed questionnaire.ResultsPatients were aged between 17 and 68 years with a sex ratio (M/F) of 1. Mood disorders accounted for 24.6% of disorders (N=17) whereas schizophrenia 66.7% (N=46). Patients resided in urban areas in 88.6% of cases (N=69). The average number of hospitalizations was 2.7 with extremes ranging from 0 to 14. The average time between the onset of the symptoms and the first consultation was 1 year. The mean time from onset to hospitalization was 4.37 years. The rate of consulting a psychiatrist prior to admission was 42.8%. The diagnosis was corrected during the follow-up of the patients in 24.3% of cases. Conventional neuroleptics were prescribed as first-line treatment in 42.85% of cases. Due to poor tolerance or ineffectiveness of the treatment, 31.42% of patients had to change treatment.ConclusionsPatients, who were desperate to find an adequate treatment for their disorders, put a lot of hope in the Razi psychiatric hospital. But after several years of evolution of their disease, we are faced with a therapeutic impasse. Raising awareness of mental illnesses is necessary for an early and adequate treatment.DisclosureNo significant relationships.

Surinfection of the Renal Graft by a Strain of Klebsiella pneumonia Oxa 48 Producer and Therapeutic Impasse

The surinfection of the renal graft by multi-resistant germs constitutes a serious complication, which can engage the functional and vital prognosis in renal transplant patients. It is responsible for a problem of therapeutic management and of the benefit/risk ratio between antibiotic therapy at therapeutic doses and the contraindications linked to renal insufficiency and therapeutic impasse. This work reports the case of a kidney transplant recipient who died following complications of a superinfection of the graft by a strain of Klebsiella pneumoniae producing OXA 48. The purpose of this observation is to underline the nosocomial risk in kidney transplant patients and the difficulty of the therapeutic management of these multi-resistant infections.

Rapid Disease Control in First-Line Therapy-Resistant Mucous Membrane Pemphigoid and Bullous Pemphigoid with Omalizumab as Add-On Therapy: A Case Series Of 13 Patients.

The role of IgE autoantibodies has been demonstrated in the pathogenesis of bullous pemphigoid for many years. Recently, omalizumab (OMZ), a humanized monoclonal anti-IgE antibody that depletes total serum IgE, has been used off-label in a few case series of bullous pemphigoids demonstrating a rapid efficacy and allowing significant improvements or complete remission as add-on therapy in first-line treatment-resistant patients. Herein, we report the largest retrospective study to evaluate OMZ effectiveness in patients with subepidermal autoimmune blistering diseases. Our series included 13 patients from a single center with bullous pemphigoid or mucous membrane pemphigoid, of whom 7 had mucous membrane involvement. OMZ was added to the unchanged immunosuppressive therapies. Detailed clinical and immunological data during the first year were collected, notably for specific anti-BP180-NC16A IgE and IgG, and the median total follow-up was 30 months (range: 3–81). Our series demonstrated that OMZ induced a significant improvement in pruritus, urticarial score, and daily blister count on day 15, allowing disease control to be achieved in a 1-month median time and complete remission (CR) in a 3-month median time in 85% of these patients previously in therapeutic impasse. At the end of the follow-up, 31% of patients achieved CR on minimal therapy after OMZ weaning without relapses, and 54% achieved CR on OMZ continuation with a minimal dose of concomitant treatment. Two patients experienced therapeutic failure (15%). At baseline, clinical variables reflecting activity were significantly positively correlated with eosinophil blood count, total IgE serum level, specific anti-BP180 IgE and IgG. While baseline anti-BP180 IgG and specific anti-BP180 IgE were significantly positively correlated, only the two patients who experienced a therapeutic failure with OMZ did not fit with this correlation, demonstrating elevated levels of anti-BP180 IgG with no measurable BP180-specific IgE. Follow-up of immunological variables demonstrated a rapid decrease of eosinophilia towards normalization, whereas a slower decline towards negativation was observed over 1 year for anti-BP180 IgG and anti BP180 IgE in patients who responded to OMZ. This case series demonstrated that OMZ is a rapidly effective biologic therapy for refractory bullous pemphigoid and mucous membrane pemphigoid, permitting rapid disease control and reduction of concomitant therapeutics.

Leçons d’un maître en déplacement de tissus : études des carnets opératoires du médecin général Gustave Ginestet dans ses années Foch (1945–1959)

The surgical notebooks (1945-1959) of General Gustave Ginestet are the last direct testimony of the quintessential period in which autoplastic techniques were used, before their twilight, favored by the advent of axial pedicle flaps, musculocutaneous flaps and later free flaps. They summarize all the refinements of the experience accumulated at the National Center for Reconstructive Surgery (Centre Médico-Chirurgical Foch-Suresnes). They appear to be more informative than the various books of the time, which were intended for an experienced public or for those benefiting from a companionship, thus eluding a certain number of precautionary advice, which are undoubtedly tacit but essential to obtain a successful operation in the hypothesis of their current use. This paper aims to establish the principles of historical surgical techniques and to integrate them into the management of patients in therapeutic impasse. One hundred and seven clinical situations requiring tissue displacement were analyzed by reconstructed region and by type of flap used. This technical view of the past, as close as possible to the daily practice of a famous reconstructive surgery center, does not offer absolute methodological or technical precepts. From the surgical notebooks studied, the only thing that emerges is a rigorous approach that allows us to contain a permanent doubt and an experimental process. This notion of constant evolution of the autoplastic practice, guided by its errors, intuitions and beliefs, highlights the importance of a surgical culture, which, with a humanistic approach, must be nourished by the paths of the past.

Evaluation of the antibacterial activity of three types of Vernonia amygdalina Del. leaf extract sold in the markets of Lomé-Togo

Nowadays, the emergence of multi-resistant bacteria and the absence of new antibiotics are an increasing risk of therapeutic impasse. Nutraceuticals are plants which are reputed to have therapeutic properties and which are consumed as food. One of these plants consumed as a leafy vegetable, having amoebicidal properties and very popular among togolese populations is Vernonia amygdalina. The objective of this work was to evaluate the antibacterial activity of three types of V. amygdalina leaf extracts. The extracts were obtained by maceration of dried leaf powder (hydroethanolic 30:70), by decoction of fresh leaves and crushed boiled leaves (FEBEVA). The evaluation of the antibacterial activity of the extracts was carried out by the diffusion method and microdilution. The decoctate had a bactericidal effect on S. aureus and K. pneumoniae. FEBEVA was only activated on day 7 and only with a concentration of 400 mg. Phytochemical screening revealed secondary metabolites such as saponosides, tannins, triterpenes, polyphenols, sterols, alkaloids. This work has provided a scientific basis for the use of Vernonia amygdalina in traditional pharmacopoeia, particularly in the treatment of bacterial pathologies.

Bactéries multirésistantes et hautement résistantes émergentes : définition et mécanismes de résistance d'intérêt épidémiologique

AbstractAntibiotic resistance is a hot public health issue. Former MRSA gives the way to ESBL, and recently brand new CRE and VRE. New antibiotics are discovered rarely, and therapeutic impasses become real. Screening and identification of the resistance mechanisms (MRSA, ESBL, CRE,VRE) is essential to contain cross contamination and decrease antibiotic misuse.

Ras-p53 genomic cooperativity as a model to investigate mechanisms of innate immune regulation in gastrointestinal cancers.

Despite increasingly thorough mechanistic understanding of the dominant genetic drivers of gastrointestinal (GI) tumorigenesis (e.g., Ras/Raf, TP53, etc.), only a small proportion of these molecular alterations are therapeutically actionable. In an attempt to address this therapeutic impasse, our group has proposed an innovative extreme outlier model to identify novel cooperative molecular vulnerabilities in high-risk GI cancers which dictate prognosis, correlate with distinct patterns of metastasis, and define therapeutic sensitivity or resistance. Our model also proposes comprehensive investigation of their downstream transcriptomic, immunomic, metabolic, or upstream epigenomic cellular consequences to reveal novel therapeutic targets in previously “undruggable” tumors with high-risk genomic features. Leveraging this methodology, our and others’ data reveal that the genomic cooperativity between Ras and p53 alterations is not only prognostically relevant in GI malignancy, but may also represent the incipient molecular events that initiate and sustain innate immunoregulatory signaling networks within the GI tumor microenvironment, driving T-cell exclusion and therapeutic resistance in these cancers. As such, deciphering the unique transcriptional programs encoded by Ras-p53 cooperativity that promote innate immune trafficking and chronic inflammatory tumor-stromal-immune crosstalk may uncover immunologic vulnerabilities that could be exploited to develop novel therapeutic strategies for these difficult-to-treat malignancies.

Urgent unmet needs in the care of bacterial keratitis: An evidence-based synthesis

Bacterial corneal infections, or bacterial keratitis (BK), are ophthalmic emergencies that frequently lead to irreversible visual impairment. Though increasingly recognized as a major cause of global blindness, modern paradigms of evidence-based care in BK have remained at a diagnostic and therapeutic impasse for over half a century. Current standards of management – based on the collection of corneal cultures and the application of broad-spectrum topical antibiotics – are beset by important yet widely underrecognized limitations, including approximately 30% of all patients who will develop moderate to severe vision loss in the affected eye. Though recent advances have involved a more clearly defined role for adjunctive topical corticosteroids, and novel therapies such as corneal crosslinking, overall progress to improve patient and population-based outcomes remains incommensurate to the chronic morbidity caused by this disease. Recognizing that the care of BK is guided by the clinical axiom, “time equals vision”, this chapter offers an evidence-based synthesis for the clinical management of these infections, underscoring critical unmet needs in disease prevention, diagnosis, and treatment.

O-012 Diagnostic strategies

Abstract text Most discussions of the management of recurrent implantation failure (RIF) will start by expressing the criteria for ‘diagnosis’ of the condition. And here lies our first mistake. Defining RIF as a condition diagnosable in terms of a standard number of embryos transferred without achieving pregnancy suggests that is a medical diagnosis in itself, for which, like other diseases, an optimal treatment strategy exists. But the failure of our field to improve outcomes in patients who suffer RIF suggest that we have approaching the condition wrongly. RIF is NOT medical disease diagnosed by applying simple clinical criteria. It is a personal experience suffered by patients and which can uncomfortably challenge their doctors. IN order to address the mistake we have made in our approach to RIF, we need to recognise that the condition needs to be recognized in a different way. In practical clinical terms, RIF can be considered to have occurred at the point when the patient(s) and their doctor conclude that further action is necessary beyond the standard work up and treatment approach for IVF. Our failure to understand what constitutes RIF has also resulted in large and methodologically sound trials of interventions proposed to ‘treat’ RIF missing the target. Based as most have been on the premise that RIF is a disease for which the optimal treatment exists if we can just find it, these trials are largely destined to produce negative results, as those in whom the intervention was effective cannot be differentiated form those in whom it might have caused harm. The resulting ‘zero sum’ requires the study authors to write off the studied intervention as ‘ ineffective’ potentially depriving certain patients of a useful treatment. So how can we address the therapeutic impasse that we have created? The answer is surely clear. When our standard best practices fail to result in pregnancy after IVF in a particular patient, we simply need to try to understand why. This requires the classic diagnostic approach: consider RIF a symptom; look for signs that might explain it and order investigations to pin down the cause(s). So what diagnostic approaches should be applied? In many cases, the embryo factor will already have been subject to considerable scrutiny. When treatment continues to fail, the focus will therefore tend to turn at this point to the patients. This is where the story begins to look more positive. In recent years it has become clear how active a role the endometrium plays in embryo implantation. As these novel endometrial factors have become elucidated, clinical tests of their function have begun to emerge. While many contributory factors merit investigation when RIF is considered to have arisen, this lecture will introduce the concept of the ‘endometrial diagnostic toolkit’ that promises to enable us to treat RIF on the basis of individual rationale rather than blind hope, and to test the efficacy of targeted rather than blind interventions. O-013 Therapeutic aspects

The inverse paradigm and the ancestral cell of IDH-wildtype glioblastoma.

Rethinking IDH-wildtype glioblastoma through its unique features can help researchers find innovative and effective treatments. It is currently emerging that, after decades of therapeutic impasse, some traditional concepts regarding IDH-wildtype glioblastoma need to be supplemented and updated to overcome therapeutic resistance. Indeed, multiple clinical aspects and recent indirect and direct experimental data are providing evidence that the supratentorial brain parenchyma becomes entirely and quiescently micro-infiltrated long before primary tumor bulk growth. Furthermore, they are indicating that the known micro-infiltration that occurs during the IDH-wildtype glioblastoma growth and evolution is not at the origin of distant relapses. It follows that the ubiquitous supratentorial brain parenchyma micro-infiltration as a source for the development of widespread distant recurrences is actually due to the silent stage that precedes tumor growth rather than to the latter. All this implies that, in addition to the heterogeneity of the primary bulk, there is a second crucial cause of therapeutic resistance that has never hitherto been identified and challenged. In this regard, the ancestral founder cancer stem cell (CSC) appears as the key cell that can link the two causes of resistance.

Revision of trapeziectomy failures in thumb base osteoarthritis: retrospective analysis of ten cases and review of the literature

Controversy persists around trapeziectomy as standard of care in thumb base osteoarthritis. The difficulty of management of failure requires the utmost caution in choice of the initial technique. We here report a retrospective series of 10 revision procedures following trapeziectomy, supported by a review of literature. The main cause of revision was collapse of the thumb column resulting in arthrogenic contact of the first metacarpal with the scaphoid. At a mean 73.3 months’ follow-up, 5 patients had to undergo additional surgery. Mean VAS pain score was 2.9; 5 patients were pain-free. Strength was more severely impaired than joint motion, resulting in disappointing functional results. The present outcomes are consistent with the literature, which mostly comprises heterogeneous series, making it impossible draw conclusions to guide practice. The most common option seems to be to perform a new ligament procedure, with or without tendon or pyrocarbon interposition, and was the one that provided the only good result in the present series. Other techniques (composite graft, non-autogenic interposition, scaphometacarpal prosthesis) seem promising, and deserve large-scale evaluation. Thus, the gold-standard status of trapeziectomy should be weighed against the observation of these multi-operated patients in situations of therapeutic impasse. Should indications for first-line trapeziectomy be restricted, especially in patients with a revision risk factor? Level of evidence4.

Bipolar disorder, cardiac comorbidity and therapeutic impasse: A case report

IntroductionBipolarDisorders (BD) are regarded as a multidimensionaldiseaseinvolvingbothpsychological and physicaldeterminants. Althoughmood dimension andthymicinstability areconsidered as the « core » aspect of bipolardisorders, itis crucial to note thatsomaticproblemsfrequentlyoccur in BD,deeplyworsening the prognosis.ObjectivesHerewedescribea case of atwentyyearshistory of psychiatricimpairment, diagnosedlaterwithcardiac malformation.MethodsFemale patient H.G has been admitted for the first time to psychiatric department ‘A’ of Razi Hospital,treated for type 1 bipolar disorder since 2004 with poor therapeutic compliance. We reviewed the clinical and paraclinical data.ResultsThe patient was hospitalized for a severe manic episode with psychotic features, without cardiac personal history. The patient was asymptomatic and physical examination showed no abnormalities. Following a routine electrocardiogram, an acute coronary syndrom was discovered (inverted T waves seen in V1 to V6). Cardiac troponins were not elevated. According to cardiology recommandations, ischemic heart disease could not be ruled out and extensive cardiovascular investigations were needed. Antipsychotics and mood stabilizors were contraindicated.Therefore, the manic episode could only be managed using benzodiazepines. Given contradictions between clinical, electrocardioagraphic and imaging findings,coronary angiography was necessary. Results showed no significant stenosis of coronary arteries and a myocardial bridging of the left anterior descending artery and we were able to put her on antipsychiotics and moodstabilizer, almost two months after her admission.ConclusionsThis case underlines the significant impact of somatic comorbidities in therapeutic management of bipolar disorders. Cardiovascular diseases in particular cause a delay in treatment initiation and an increase in patient length of hospital stay.DisclosureNo significant relationships.

Being psychotic is not necessarily being ill: Psychotic continuum and the relevance of lacanian psychoanalytic approach

IntroductionThe notion of subclinical psychosis is as old as Eugen Bleuler’s work on schizophrenia. It is also consistent with psychodynamic theories (see PDM-2) on the organization of personality on different levels including, among others, a psychotic level of personality organization. Research on the continuum of psychosis has offered substantial support to the view that psychotic phenotypes are significantly more prevalent than clinical psychosis.ObjectivesThis may imply that being “psychotic” is not necessarily being ill. This assumption raises important theoretical and clinical questions: what causes psychosis to manifest itself clinically and, conversely, what possibly prevents it from doing so?MethodsAt the same time, it potentially frees psychiatry from certain diagnostic and therapeutic impasses. It allows for a shift of emphasis from misguiding classifications and often frustrating “evidence-based” therapeutic attempts to a more personalized approach.ResultsDiagnosis may thus rely on psychoanalytical “markers” or “indicators” regarding the subject (e.g. deficits in the symbolic register, dysregulated rapport with one’s body, problematic inscription in social relations etc.) at least as much as on symptomic phenomenology. Therapy may also take advantage of and deploy the unique coping strategies employed by the psychotic individual.ConclusionsThe diagnostic and therapeutic insights offered by Lacanian psychoanalysis create the possibility of a fruitful theoretical, diagnostic and therapeutic approach for clinical and subclinical psychotic conditions; indicate that psychoanalysis is indispensable for clinical psychiatry; and signal the possibility of a time-honored alternative to the in-vogue neurocognitive paradigm of “personalized” psychiatry.DisclosureNo significant relationships.

Neuropilin 1 and Neuropilin 2 gene invalidation or pharmacological inhibition reveals their relevance for the treatment of metastatic renal cell carcinoma

BackgroundDespite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.MethodsWe correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs.ResultsKnock-out of the NRP1 and NRP2 genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients.ConclusionsOur study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.

Réflexions sur les psychothérapies par le jeu vidéo

Réflexions sur les psychothérapies par le jeu vidéo