[A guide to psychiatric prescribing in pregnancy, postpartum and breastfeeding]. / Guide de prescription psychiatrique pendant la grossesse, le postpartum et l'allaitement.

Perinatal psychopharmacology is an emerging specialty that is gradually developing alongside perinatal psychiatry. The management of psychiatric disorders during the perinatal period is a challenge for perinatal practitioners due to the multiple changes occurring during this crucial period. This little-known specialty still suffers from inappropriate considerations on the impact of psychotropic treatments on the mother and the infant during pregnancy and postpartum, which can promote a deficiency in perinatal psychic care. However, the risks associated with insufficient management of mental health are major, impacting both the mental and physical health of the mother and the infant. In this paper, we propose a perinatal psychopharmacology prescription guide based on available scientific evidence and international and national recommendations. We thus propose a decision-making process formalized on simple heuristics in order to help the clinician to prescribe psychotropic drugs during the perinatal period.

[Belief updating and mood congruence in depressive disorder]. / Mise à jour des croyances et congruence à l'humeur dans le trouble dépressif.

Depressive disorder is characterized by a polymorphic symptomatology associating emotional, cognitive and behavioral disturbances. One of the most specific symptoms is negative beliefs, called congruent to mood. Despite the importance of these beliefs in the development, the maintenance, and the recurrence of depressive episodes, little is known about the processes underlying the generation of depressive beliefs. In this paper, we detail the link between belief updating mechanisms and the genesis of depressive beliefs. We show how depression alters information processing, generating cognitive immunization when processing positive information, affective updating bias related to the valence of belief and prediction error, and difficultie to disengage from negative information. We suggest that disruption of belief-updating mechanisms forms the basis of belief-mood congruence in depression.

[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

[Ketamine, psilocybin, and rapid acting antidepressant: new promise for psychiatry?] / Kétamine, psilocybine, et antidépresseurs d'action rapide : de nouvelles promesses pour la psychiatrie?

The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in hallucinogenic substances such as psilocybin targeting the serotonergic signaling 5HT2A and neurosteroid allosteric modulator of γ-aminobutyric acid (GABAA) receptors such as brexanolone. Unlike conventional treatments, these modulators of glutamatergic, serotonergic and GABAergic systems exert a rapid antidepressant effect ranging from 24hours to a week. Apart from their clinical interest and the fantasized search for a "miracle" molecule that jointly meets the expectations of patients and clinicians, these new targets could lead to the identification of potential new biomarkers for the development of rapid-acting antidepressants and redefine therapeutic strategies in mood disorders.

Prevalence and impact of patient suicide in psychiatrists: Results from a national French web-based survey.

BACKGROUND: Patient suicide (PS) is known to be a frequent and challenging occupational hazard for mental health professionals. No study previously explored the prevalence and impact of PS in a large sample of French psychiatrists. METHOD: A national web-based survey was performed between September and December 2019 to assess (a) the prevalence of the exposure to PS, (b) the emotional, traumatic and professional impacts of PS, and (c) the perceived support in the aftermath of PS in French psychiatrists. Participants were contacted through email to answer the online 62-item questionnaire, including a measure of traumatic impact through the Impact of Event Scale-Revised. Emotional and professional impacts and perceived support were assessed through dedicated items. RESULTS: A total of 764 psychiatrists fully completed the survey. Of them, 87.3% reported an exposure to PS and 13.7% reported PTSD symptoms afterward. Guilt, sadness and shock were the most frequent emotions. Among the exposed psychiatrists, 15.1% have temporarily considered changing their career path. The most emotionally distressing PS occurred during their ten first years of practice or during residency. A total of 37.1% of respondents felt unsupported and 50.4% reported that no team meeting had been organized in the aftermath. The feeling of responsibility for the death was strongly associated with negative impacts. CONCLUSION: Our results entail considerations to prevent negative mental health outcomes in psychiatrists after PS. Notably, our results advocate for the implementation of educational programs during psychiatric residency and postvention programs in healthcare settings to effectively help psychiatrists in dealing with PS.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

[Challenges for psychotropics in the context of the SARS-Cov-2 pandemic]. / Enjeux de l'utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2.

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.

[Coronavirus: Predictive brain and terror management]. / Coronavirus : cerveau prédictif et gestion de la terreur.

Emerging infectious diseases like Covid-19 cause a major threat to global health. When confronted with new pathogens, individuals generate several beliefs about the epidemic phenomenon. Many studies have shown that individual protective behaviors largely depend on these beliefs. Due to the absence of treatment and vaccine against these emerging pathogens, the relation between these beliefs and these behaviors represents a crucial issue for public health policies. In the premises of the Covid-19 pandemic, several preliminary studies have highlighted a delay in the perception of risk by individuals, which potentially holds back the implementing of the necessary precautionary measures: people underestimated the risks associated with the virus, and therefore also the importance of complying with sanitary guidelines. During the peak of the pandemic, the salience of the threat and of the risk of mortality could then have transformed the way people generate their beliefs. This potentially leads to upheavals in the way they understand the world. Here, we propose to explore the evolution of beliefs and behaviors during the Covid-19 crisis, using the theory of predictive coding and the theory of terror management, two influential frameworks in cognitive science and in social psychology.

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.

Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review.

OBJECTIVE: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. METHODS: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. RESULTS: We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: (1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; (2) age (the elderly form the population most vulnerable to the coronavirus); (3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist/infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. DISCUSSION: French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.

[Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review]. / Assurer les soins aux patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

OBJECTIVE: The lack of ressources and coordination to face the epidemic of coronavirus raises concerns for the health of patients with mental disorders in a country where we keep in memory the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims at proposing guidance to ensure mental health care during the SARS-CoV epidemy in France. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature and local initiatives in France. RESULTS: We identified four types of major vulnerabilities in patients suffering from mental disorders during this pandemic: (1) medical comorbidities that are more frequently found in patients suffering from mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which represent risk factors for severe infections with Covid-19; (2) age (the elderly constituting the population most vulnerable to coronavirus); (3) cognitive and behavioral troubles which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability due to stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly adapted to psychiatric establishments in a context of major shortage of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds are closed, wards have a high density of patients, mental health community facilities are closed, medical teams are understaffed and poorly trained to face infectious diseases. We could also face major issues in referring patients with acute mental disorders to intensive care units. To maintain continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of Covid+ units. These units are under the dual supervision of a psychiatrist and of an internist/infectious disease specialist; all new entrants should be placed in quarantine for 14 days; the nurse staff should benefit from specific training, from daily medical check-ups and from close psychological support. Family visits would be prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management should be organized with the possibility of home visits, in order to support them when they get back home and to help them to cope with the experience of confinement, which is at risk to induce recurrences of mental disorders. The total or partial closure of mental health community facilities is particularly disturbing for patients but a regular follow-up is possible with telemedicine and should include the monitoring of the suicide risk and psychoeducation strategies; developing support platforms could also be very helpful in this context. Private psychiatrists have also a crucial role of information with their patients on confinement and barrier measures, but also on measures to prevent the psychological risks inherent to confinement: maintenance of sleep regularity, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. DISCUSSION: French mental healthcare is now in a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the containment of the general population.

[Psychopharmacotherapeutic guidelines : a challenge during health crisis]. / Recommandations psychopharmacothérapeutiques : un défi en temps de crise sanitaire.

The construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward.

Réaliser des recommandations pharmacothérapeutiques est une démarche complexe, plus encore dans une période de crise sanitaire, comme celle que nous traversons avec la pandémie liée au SARS-CoV-2. En psychiatrie, les préconisations formulées se doivent de rappeler la légitime prudence à adopter dans le maniement des psychotropes, dans un contexte qui, par ailleurs, présente certaines de ces médications comme potentiellement prophylactiques de la COVID-19. Ces enjeux contradictoires sont débattus, les concepts méthodologiques de l'élaboration des recommandations sont rappelés.

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Is major depression a cognitive disorder?

This is a review of cognitive abilities in major depression, which is associated with attention problems, memory deficit and wide impairment in executive functions. Depressed patients show two major cognitive biases: excessive processing of negatively valenced emotional stimuli; and increased self-focus. Both of these biases help to facilitate the integration of negative self-related information in depressed patients and to maintain their negative mood. Brain imaging studies suggest that this cognitive impairment is characterized by abnormal cooperation between the cognitive and limbic networks involved in cognitive control and self-referential processing. In general, depression is a disorder of multiple networks with emotional, cognitive and emotional symptoms. Among these symptoms, cognition is a major determinant of functional and social outcomes.

Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Hypothyroidism in hospitalized elderly patients: a sign of worse prognosis.

PURPOSE: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients. METHODS: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression. RESULTS: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]. CONCLUSION: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

[Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review]. / Facteurs prédictifs de la réponse antidépressive à la kétamine dans les épisodes dépressifs majeurs résistants : revue de la littérature.

OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response. METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial ß-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. CONCLUSIONS: In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in attention tests were also predictive to a good response. These predictive factors could be more specific to ketamine. With these different predictor factors (clinical and biological), it could be interesting to develop clinical strategies to personalize ketamine's administration.

[Cognition - the core of major depressive disorder]. / La cognition au cœur de la dépression.

Cognitive deficits have been only recently recognized as a major phenotype determinant of major depressive disorder, although they are an integral part of the definition of the depressive state. Congruent evidence suggest that these cognitive deficits persist beyond the acute phase and may be identified at all ages. The aim of the current study was to review the main meta-analyses on cognition and depression, which encompasses a large range of cognitive domains. Therefore, we discuss the "cold" (attention, memory, executive functions) and "hot" (emotional bias) cognitive impairments in MDD, as well as those of social cognition domains (empathy, theory of mind). Several factors interfere with cognition in MDD such as clinical (melancholic, psychotic...) features, age, age of onset, illness severity, medication and comorbid condition. As still debated in the literature, the type of relationship between the severity of cognitive symptoms and functioning in depression is detailed, thus highlighting their predictive value of functional outcome, independently of the affective symptoms. A better identification of the cognitive deficits in MDD and a monitoring of the effects of different treatments require appropriate instruments, which may be developed by taking advantage of the increasing success of computing tools. Overall, current data suggest a core role for different cognitive deficits in MDD, therefore opening new perspectives for optimizing the treatment of depression.

CyberKnife robotic image-guided stereotactic radiotherapy for oligometastic cancer : A prospective evaluation of 95 patients/118 lesions.

PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray Inc. Sunnyvale, USA)-based stereotactic radiotherapy (CBK-SRT) for oligometastic cancer patients. PATIENTS AND METHODS: Between May 2007 and December 2009, 95 patients with a total of 118 lesions underwent CBK-SRT (median dose 24 Gy in 3 fractions). INCLUSION CRITERIA: adult patients with limited volume cancer; suitability for SRT but not for other local therapies. Primary diagnoses included breast, lung, head and neck, gastrointestinal and other malignancies. Prostate cancer patients were excluded. Concomitant systemic therapy was given in 40 % of cases and median follow-up was 12 months. Toxicity and tumor response were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale and Response Evaluation Criteria in Solid Tumors RECIST. RESULTS: Toxicity was rare and observed mainly in patients with comorbidities or uncontrolled cancer. Out of 87 evaluable lesions, complete radiological response, partial response, stabilization and progressive disease were observed in 15 (17 %), 25 (29 %), 34 (39 %) and 13 (15 %) lesions, respectively. Upon restricting the analysis to lesions treated with CBK-SRT alone (no concomitant therapy), response- and local control (LC) rates remained similar. Actuarial 3-year in-field progression-free survival- (i.e. LC), progression-free survival- (PFS) and overall-survival (OS) rates were 67.6, 18.4, and 31.2 %, respectively. LC was reduced in cases of early recurrence. OS- and cause-specific survival (CSS) rates were significantly lower in patients treated for visceral lesions. Failures were predominantly out-field. CONCLUSION: CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that provides long-term in-field tumor control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.