Evolution of impulsivity levels in relation to early cannabis use in violent patients in the early phase of psychosis.

BACKGROUND: Prevention of violent behaviors (VB) in the early phase of psychosis (EPP) is a real challenge. Impulsivity was shown to be strongly related to VB, and different evolutions of impulsivity were noticed along treatments. One possible variable involved in the relationship between VB and the evolution of impulsivity is cannabis use (CU). The high prevalence of CU in EPP and its relationship with VB led us to investigate: 1/the impact of CU and 2/the impact of early CU on the evolution of impulsivity levels during a 3-year program, in violent and non-violent EPP patients. METHODS: 178 non-violent and 62 violent patients (VPs) were followed-up over a 3 year period. Age of onset of CU was assessed at program entry and impulsivity was assessed seven times during the program. The evolution of impulsivity level during the program, as a function of the violent and non-violent groups of patients and CU precocity were analyzed with linear mixed-effects models. RESULTS: Over the treatment period, impulsivity level did not evolve as a function of the interaction between group and CU (coef. = 0.02, p = 0.425). However, when including precocity of CU, impulsivity was shown to increase significantly only in VPs who start consuming before 15 years of age (coef. = 0.06, p = 0.008). CONCLUSION: The precocity of CU in VPs seems to be a key variable of the negative evolution of impulsivity during follow-up and should be closely monitored in EPP patients entering care since they have a higher risk of showing VB.

FOLFIRI plus BEvacizumab or aFLIbercept after FOLFOX-bevacizumab failure for COlorectal cancer (BEFLICO): An AGEO multicenter study.

After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR + PR + SD) and safety. We included 681 patients from 36 centers, 326 and 355 in the aflibercept and bevacizumab groups, respectively. Median age was 64.2 years and 45.2% of patients were men. Most patients had RAS-mutated tumors (80.8%) and synchronous metastases (85.7%). After a median follow up of 31.2 months, median OS was 13.0 months (95% CI: 11.3-14.7) and 10.4 months (95% CI: 8.8-11.4) in the bevacizumab and aflibercept groups, respectively (P < .0001). Median PFS was 6.0 months (95% CI: 5.4-6.5) and 5.1 months (95% CI: 4.3-5.6) (P < .0001). After adjustment on age, PS, PFS of first line, primary tumor resection, metastasis location and RAS/BRAF status, bevacizumab was still associated with better OS (HR: 0.71, 95% CI: 0.59-0.86, P = .0003). FOLFIRI-bevacizumab combination was associated with longer OS and PFS, and a better tolerability, as compared to FOLFIRI-aflibercept after progression on FOLFOX-bevacizumab.

Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers.

Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI.

Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study.

Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endpoint was the progression-free survival (PFS) in a population receiving first-line chemotherapy. Associations between chemotherapy regimen and survival were evaluated using a Cox regression model and inverse of probability of treatment weighting (IPTW) methodology in order to limit potential biases. Overall, 342 patients with dMMR/MSI mCRC were included. Median PFS and overall survival (OS) on first-line chemotherapy were 6.0 and 26.3 months, respectively. For second-line chemotherapy, median PFS and OS were 4.4 and 21.6 months. Longer PFS (8.1 vs. 5.4 months, p = 0.0405) and OS (35.1 vs. 24.4 months, p = 0.0747) were observed for irinotecan-based chemotherapy compared to oxaliplatin-based chemotherapy. The association was no longer statistically significant using IPTW methodology. In multivariable analysis, anti-VEGF as compared to anti-EGFR was associated with a trend to longer OS (HR = 1.78, 95% CI 1.00-3.19, p = 0.0518), whatever the backbone chemotherapy used. Our study shows that dMMR/MSI mCRC patients experienced short PFS with first-line chemotherapy with or without targeted therapy. OS was not different according to the chemotherapy regimen used, but a trend to better OS was observed with anti-VEGF. Our study provides some historical results concerning chemotherapy in dMMR/MSI mCRC in light of the recent nonrandomized trials with immune checkpoint inhibitors.

Predicting physically violent misconduct in prison: A comparison of four risk assessment instruments.

Violence in correctional facilities is an important issue for both prisoners and prison staff. Risk assessment instruments have demonstrated their accuracy in predicting the risk of (re) offending and institutional violence in psychiatric settings, but less is known about their ability to predict violent misconduct in prison. The present study applied four risk assessment instruments (Structured Assessment of Protective Factors for violence risk, Historical Clinical Risk Management-20, Psychopathy checklist - Revised, and Violent Risk Appraisal Guide) to 52 violent offenders in a Swiss prison in order to evaluate the instruments' predictive validities. Outcomes were instances of physically violent, other and any misconduct as recorded in prison files during the 12 months following the prisoners' assessments. Approximately 15% of offenders committed physically violent misconduct and approximately 42% committed any misconduct. The results show that mainly dynamic assessment tools are as good predictors of physically violent misconduct as mainly static assessment tools. Targeting dynamic factors could increase the effectiveness of interventions to reduce the risk of physical violence in prison.

Segmental morphometrics of the olive baboon (Papio anubis): a longitudinal study from birth to adulthood.

The linear dimensions and inertial characteristics of the body are important in locomotion and they change considerably during the ontogeny of animals, including humans. This longitudinal and ontogenetic study has produced the largest dataset to date of segmental morphometrics in a Catarrhini species, the olive baboon. The objectives of the study were to quantify the changes in body linear and inertial dimensions and to explore their (theoretical) mechanical significance for locomotion. We took full-body measurements of captive individuals at regular intervals. Altogether, 14 females and 16 males were followed over a 7-year period, i.e. from infancy to adulthood. Our results show that individual patterns of growth are very consistent and follow the general growth pattern previously described in olive baboons. Furthermore, we obtained similar growth curve structures for segment lengths and masses, although the respective time scales were slightly different. The most significant changes in body morphometrics occurred during the first 2 years of life and concerned the distal parts of the body. Females and males were similar in size and shape at birth. The rate and duration of growth produced substantial size-related differences throughout ontogeny, while body shapes remained very similar between the sexes. We also observed significant age-related variations in limb composition, with a proximal shift of the centre of mass within the limbs, mainly due to changes in mass distribution and in the length of distal segments. Finally, we observed what we hypothesize to be 'early biomechanical optimization' of the limbs for quadrupedal walking. This is due to a high degree of convergence between the limbs' natural pendular periods in infants, which may facilitate the onset of quadrupedal walking. Furthermore, the mechanical significance of the morphological changes observed in growing baboons may be related to changing functional demands with the onset of autonomous (quadrupedal) locomotion. From a wider perspective, these data provide unique insights into questions surrounding both the processes of locomotor development in primates and how these processes might evolve.

Kinematics and spatiotemporal parameters of infant-carrying in olive baboons.

In the field of biomechanics of quadrupedal locomotion in primates, infant-carrying has received little attention. This study presents the first biomechanical study of infant-carrying in captive female olive baboons (Papio anubis). We test whether females carrying infants conform 1) to the Support Polygon Model (Rollinson and Martin: Symp Zool Soc Lond 48 (1981) 377-427) of gait selection, according to which diagonality should decrease when the infant is carried cranially and increase when the infant is carried dorsally and caudally; 2) to Biewener's (Biewener: Science 245 () 45-48) theory of limb postures, according to which females should extend their hind limbs more due to infant load, especially in the later stages when the infant is not fully autonomous but relatively heavy. This study focuses on the sagittal kinematics of quadrupedal gaits (joint angles and spatiotemporal parameters) of four females with and without infant loads at the CNRS Primatology Station (France). High-speed video recordings were made using the technical platform "Motion Analysis of Primates" available in the animals' place of life. Regarding diagonality, our results do not fully conform to those predicted by the Support Polygon Model of gait selection; however, the model cannot be rejected at this stage in experiment. With regard to limb posture, our results do not support Biewener's (Biewener: Science 245 () 45-48) theory: loaded females do not extend their hind limbs more as predicted; on the contrary, the hind limbs tend to be more flexed when the infant they carry is relatively heavy.

Successful Treatment of Captive Common Marmosets (Callithrix jacchus) Infested with Common Cat Fleas (Ctenocephalides felis) by Using Topical Imidacloprid and Environmental Control Measures.

Fleas are ectoparasites affecting many animal species but reports in captive nonhuman primates are rare and mainly concern pet monkeys. Moreover, to the authors' knowledge, a detailed report on marmosets is not known at present. This case describes the clinical signs, diagnosis, treatment and follow-up of a flea infestation by Ctenocephalides felis in a captive colony of common marmosets. Fleas, flea feces and skin lesions were identified on two animals during annual health screening. Subsequently, the entire colony was examined, and nearly half of the colony showed signs of infestation. Consequently, treatment was initiated for the entire colony and the environment. Animals received two topical administrations of imidacloprid (5 mg for animals <200 g and 10 mg for animals weighing >200 g) three weeks apart, and their enclosures were decontaminated using vaporizers containing permethrin, piperonyl butoxide, and pyriproxyfen. Subsequently, skin lesions were resolved and no evidence of fleas were noticed. No side effects of the treatment were observed. Stray cats were identified as the source of the infestation. Their access to the animal-related rooms was stopped. No reinfestation has been reported for 3 years. The topical application of imidacloprid appeared effective with no adverse events occurring, so may be appropriate for use in other non-human primates.

Measuring craving: A systematic review and mapping of assessment instruments. What about sexual craving?

BACKGROUND AND AIMS: Craving is central in the definition of addictive disorders because of its diagnostic and prognostic value. Its measurement is essential in clinical practice. Previous reviews provided a better overview of existing instruments; however, they do not consider emerging substances and behaviors such as sexual addictions. Our objectives were threefold: (1) to provide a systematic review of craving assessment instruments and their psychometric characteristics within a transdiagnostic approach, (2) to highlight and map their conceptual relationships and (3) to identify potential sexual craving assessment instruments. METHODS: The review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The PubMed, Embase, PsychInfo and Cochrane/Central databases were searched for publications that met the following inclusion criterion: validation studies of craving assessment instruments, regardless of target substance or behavior. The original search identified 4561 references and included 147 articles. Each selected study was a peer-reviewed publication. RESULTS: This review provides a synthesis of the psychometric properties of 36 original instruments and identified 93 variations of these instruments (e.g. translations). We were able to highlight five transdiagnostic families of instruments, each corresponding to a conceptual model. Only one instrument for assessing craving in the domain of compulsive sexual behavior, focused on pornography use, has been identified: the Pornography Craving Questionnaire. CONCLUSION: This review mapped all craving assessment instruments from a transdiagnostic perspective, finding 36 original instruments and 93 variations. The evolution of instruments to measure craving mirrors the evolution of the concept of craving which has progressively integrated cognitive, conditioning and sensory dimensions, and attests to the importance of the context of assessment. Development of an instrument to measure 'sexual craving' is needed and could be based on the data from our review.

STLV-1 Commonly Targets Neurons in the Brain of Asymptomatic Non-Human Primates.

The human T-cell leukemia virus (HTLV)-1 is responsible for an aggressive neurodegenerative disease (HAM/TSP) and multiple neurological alterations. The capacity of HTLV-1 to infect central nervous system (CNS) resident cells, together with the neuroimmune-driven response, has not been well-established. Here, we combined the use of human induced pluripotent stem cells (hiPSC) and of naturally STLV-1-infected nonhuman primates (NHP) as models with which to investigate HTLV-1 neurotropism. Hence, neuronal cells obtained after hiPSC differentiation in neural polycultures were the main cell population infected by HTLV-1. Further, we report the infection of neurons with STLV-1 in spinal cord regions as well as in brain cortical and cerebellar sections of postmortem NHP. Additionally, reactive microglial cells were found in infected areas, suggesting an immune antiviral response. These results emphasize the need to develop new efficient models by which to understand HTLV-1 neuroinfection and suggest an alternative mechanism that leads to HAM/TSP.

[New challenge for services for people with a first episode of psychosis: To integrate interventions to prevent and reduce physical aggression]. / Le nouveau défi des services destinés aux personnes présentant un premier épisode de psychose : intégrer des interventions pour prévenir et réduire les agressions physiques.

Objective Mental health services for persons presenting a first episode of psychosis include specialized interventions that are effective in treating psychosis, but they do not include treatments that prevent aggressive behaviour (AB). This article presents the results of studies in an effort to incite these services to evaluate the risk of AB and to intervene rapidly to prevent these behaviours as well as treating the psychotic disorder. Method This article presents a narrative review of the scientific studies. We have reviewed publications in French and English reporting studies, reviews, and meta-analyses focused on the antecedents, correlates, and effective treatments for AB and criminality of persons described as presenting severe mental disorder, schizophrenia, or a first episode of psychosis. Results The review of scientific studies confirms that persons developing or presenting schizophrenia are at increased risk to engage in AB, crime, and homicide relative to the general population. Before a first episode of psychosis approximately one third of patients display AB. One subgroup of these persons, those who present the highest risk of AB and criminality, have a history of conduct disorder since childhood. Another subgroup who also begin engaging in AB before a first episode of psychosis display AB as anxiety and positive symptoms increase. The association between positive psychotic symptoms and AB varies according to the phase of illness and the age of onset of AB. Further, other factors such as substance misuse (especially cannabis use), difficulty in recognizing emotions in the faces of others, impulsivity, and physical victimization are related to AB. In addition to effective treatments for psychosis and social skill training, treatment programs aimed at preventing AB and antisocial behaviours, and the associated factors are needed, as well as interventions that aim to reduce victimization. Conclusion The extant literature identifies different profiles of patients and factors associated with AB that can be identified at a first episode of psychosis. Consequently, first episode services could play an important role in preventing AB. To do this, they would need to simultaneously treat the psychosis and the AB. The implementation of such treatments would involve challenges such as convincing treatment teams of the benefits of such an approach and convincing patients needing these treatments to comply. Increasing patients' motivation and compliance remains an important challenge.

The Link Between Cannabis Use and Violent Behavior in the Early Phase of Psychosis: The Potential Role of Impulsivity.

Introduction: Recently, the literature has shown that Cannabis Use (CU) was a risk factor for Violent Behavior (VB) in patients with psychosis, and those in the early phase of psychosis (EPP). These findings are relevant because of the high prevalence of CU in this EPP, and the potential for prevention during this phase of illness. However, there is still a lack of clear explanations, supported by empirical evidence, about what underlies the link between CU and VB against other. Method: This viewpoint reviews the scientific literature on the link between CU and VB, and the involvement of impulsivity in this relationship. This last point will be addressed at clinical and neurobiological levels. Results: Recent studies confirmed that CU is particularly high in the EPP, and is a risk factor for VB in the EPP and schizophrenia. Studies have also shown that impulsivity is a risk factor for VB in psychosis, is associated with CU, and may mediate the link between CU and VB. Research suggests a neurobiological mechanism, as CU affects the structures and function of frontal areas, known to play a role in impulsive behavior. Conclusion: Scientific evidence support the hypothesis of an involvement of impulsivity as a variable that could mediate the link between CU and aggression, particularly, when CU has an early onset. However, this hypothesis should be confirmed with longitudinal studies and by taking into account confounding factors. The studies highlight the relevance of early prevention in the EPP, in addition to interventions focusing on psychotic disorders.

The Utility of Physiological Measures in Assessing the Empathic Skills of Incarcerated Violent Offenders.

Since lack of empathy is an important indicator of violent behaviors, researchers need consistent and valid measures. This study evaluated the practical significance of a potential physiological correlate of empathy compared to a traditional self-report questionnaire in 18 male violent offenders and 21 general population controls. Empathy skills were assessed with the Interpersonal Reactivity Index (IRI) questionnaire. Heart-Rate Variability (HRV) was assessed with an electrocardiogram. The RMSSD (Root Mean Square of the Successive beat-to-beat Differences), an HRV index implicated in social cognition, was calculated. There were no group differences in IRI scores. However, RMSSD was lower in the offender group. Positive correlations between RMSSD and IRI subscales were found for controls only. We conclude that psychometric measures of empathy do not discriminate incarcerated violent offenders, and that the incorporation of psychophysiological measures, such as HRV, could be an avenue for forensic research on empathy to establish translatable evidence-based information.

Sequential Treatment With Trifluridine/Tipiracil and Regorafenib in Refractory Metastatic Colorectal Cancer Patients: An AGEO Prospective "Real-World Study".

INTRODUCTION: Regorafenib (R) and trifluridine/tipiracil (FTD/TPI) are of proven efficacy in metastatic colorectal cancer (mCRC) patient's refractory to standard therapies. However, it remains unclear which drug should be administered first. PATIENTS AND METHODS: This French observational study was prospectively conducted in 11 centers between June 2017 and September 2019. All consecutive patients with chemorefractory mCRC and receiving FTD/TPI and/or R were eligible. The aim was to evaluate the efficacy and tolerability of FTD/TPI and/or R in real-world setting with adjusted analysis. RESULTS: A total of 237 mCRC patients (25% R and 75% FTD/TPI) were enrolled. As compared to R, FTD/TPI patients were significantly older and with more metastatic sites. Median OS and PFS were respectively 6.2 and 2.4 months in the FTD/TPI and 6.6 and 2.1 months in the R group. After matching 46 paired patients according to a propensity score, a trend to a longer OS (P = .58), and a significantly longer PFS (P = .048) were observed in the FTD/TPI group. In the 24% of patients receiving the R/T or T/R sequence, median OS from first treatment was similar. Tolerability profiles were similar to published data and dose reductions were more frequent in the R group. CONCLUSION: Efficacy and safety results in this real-world prospective study are in line with phase III trials. In a matched population, PFS was significantly longer in the FTD/TPI group. Despite a limited number of patients, clinical outcomes seemed similar in patients treated with the T/R or R/T sequence.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID).

BACKGROUND: The COVID-19 pandemic caused major oncology care pathway disruption. The CAPANCOVID study aimed to evaluate the impact on pancreatic adenocarcinoma (PA) - from diagnosis to treatment - of the reorganisation of the health care system during the first lockdown. METHODS: This multicentre ambispective observational study included 833 patients diagnosed with PA between September 1, 2019 and October 31, 2020 from 13 French centres. Data were compared over three periods defined as before the outbreak of COVID-19, during the first lockdown (March 1 to May 11, 2020) and after lockdown. RESULTS: During the lockdown, mean weekly number of new cases decreased compared with that of pre-pandemic levels (13.2 vs. 10.8, -18.2%; p = 0.63) without rebound in the post-lockdown period (13.2 vs. 12.9, -1.7%; p = 0.97). The number of borderline tumours increased (13.6%-21.7%), whereas the rate of metastatic diseases rate dropped (47.1%-40.3%) (p = 0.046). Time-to-diagnosis and -treatment were not different over periods. Waiting neoadjuvant chemotherapy in resectable tumours was significantly favoured (24.7%-32.6%) compared with upfront surgery (13%-7.8%) (p = 0.013). The use of mFOLFIRINOX preoperative chemotherapy regimen decreased (84.9%-69%; p = 0.044). After lockdown, the number of borderline tumours decreased (21.7%-9.6%) and advanced diseases increased (59.7%-69.8%) (p = 0.046). SARS-CoV-2 infected 39 patients (4.7%) causing 5 deaths (12.8%). CONCLUSION: This cohort study suggests the existence of missing diagnoses and of a shift in disease stage at diagnosis from resectable to advanced diseases with related therapeutic modifications whose prognostic consequences will be known after the planned follow-up. TRIAL REGISTRATION: Clinicaltrials.gov NCT04406571.

Factors associated with repetitive violent behavior of psychiatric inpatients.

A small number of psychiatric inpatients displays a large proportion of Violent Behaviors (VB). These can have a major impact on both victims and patients themselves. This study explored personal, situational and institutional risk factors and their combined effects, which could lead to repetitive VB (three or more assaults). Data from 4518 patients, aged 18 to 65, admitted to an acute psychiatric care facility, were included in the analysis. VB, defined as physical aggressions against another person, were assessed by the Staff Observation Aggression Scale-Revised. 414 VB were reported during the study period, involving 199 patients. 0.75 % of all patients were repetitively violent and committed 43% of all VB. Factors that were linked to repetitive VB were living in sheltered housing before hospitalization, suffering from schizophrenia with substance abuse comorbidity, cumulating hospitalization days and some situational factors, like the fact of being in nursing offices and pharmacies. When all personal, situational and institutional factors were considered together, the combined effects of length of stay and living in sheltered housing increased the risk of repetitive VB. We have identified a small group of vulnerable patients for whom new modalities of inter-institutional networking should be developed to prevent repetitive VB.

HSP110 as a Diagnostic but Not a Prognostic Biomarker in Colorectal Cancer With Microsatellite Instability.

Determination of microsatellite instability (MSI) using molecular test and deficient mismatch repair (dMMR) using immunohistochemistry (IHC) has major implications on colorectal cancer (CRC) management. The HSP110 T 17 microsatellite has been reported to be more monomorphic than the common markers used for MSI determination. Large deletion of HSP110 T 17 has been associated with efficacy of adjuvant chemotherapy in dMMR/MSI CRCs. The aim of this study was to evaluate the interest of HSP110 deletion/expression as a diagnostic tool of dMMR/MSI CRCs and a predictive tool of adjuvant chemotherapy efficacy. All patients with MSI CRC classified by molecular testing were included in this multicenter prospective cohort (n = 381). IHC of the 4 MMR proteins was carried out. HSP110 expression was carried out by IHC (n = 343), and the size of HSP110 T 17 deletion was determined by PCR (n = 327). In the 293 MSI CRCs with both tests, a strong correlation was found between the expression of HSP110 protein and the size of HSP110 T 17 deletion. Only 5.8% of MSI CRCs had no HSP110 T 17 deletion (n = 19/327). HSP110 T 17 deletion helped to re-classify 4 of the 9 pMMR/MSI discordance cases as pMMR/MSS cases. We did not observe any correlation between HSP110 expression or HSP110 T 17 deletion size with time to recurrence in patients with stage II and III CRC, treated with or without adjuvant chemotherapy. HSP110 is neither a robust prognosis marker nor a predictor tool of adjuvant chemotherapy efficacy in dMMR/MSI CRC. However, HSP110 T17 is an interesting marker, which may be combined with the other pentaplex markers to identify discordant cases between MMR IHC and MSI.

Prognostic factors of colorectal cancer patients with brain metastases.

INTRODUCTION: Brain metastases (BMs) from colorectal cancer (CRC) are rare (≈2%) but are increasing with the improvement of CRC prognosis. The main objective of this study was to evaluate the prognostic factors of BM from CRC. MATERIALS AND METHODS: This multicenter retrospective study included all consecutive patients with BM from CRC diagnosed between 2000 and 2017. THEORY/CALCULATION: Prognostic factors of OS were evaluated in univariate (log-rank test) and multivariate analyses (Cox regression model). These prognostic factors could help the management of patients with BM from CRC. RESULTS: A total of 358 patients were included with a median age of 65.5 years. Primary tumors were mostly located in the rectum (42.4%) or left colon (37.2%) and frequently KRAS-mutated (56.9%). The median time from metastatic CRC diagnosis to BM diagnosis was 18.5 ± 2.5 months. BMs were predominantly single (56.9%) and only supratentorial (54.4%). BM resection was performed in 33.0% of the cases and 73.2% of patients had brain radiotherapy alone or after surgery. Median OS was 5.1 ± 0.3 months. In multivariate analysis, age under 65 years, ECOG performance status 0-1, single BM and less than 3 chemotherapy lines before BM diagnosis were associated with better OS. Prognostic scores, i.e. recursive partitioning analysis (RPA), Graded Prognostic Assessment (GPA), Disease Specific-Graded Prognostic Assessment (DS-GPA), Gastro-Intestinal-Graded Prognostic Assessment (GI-GPA) and the nomogram were statistically significantly associated with OS but the most relevant prognosis criteria seemed the ECOG performance status 0-1. CONCLUSIONS: ECOG performance status, number of BM and number of chemotherapy lines are the most relevant factors in the management of patients with BM from CRC.

Early onset of cannabis use and violent behavior in psychosis.

BACKGROUND: Although evidence from psychosis patients demonstrates the adverse effects of cannabis use (CU) at a young age and that the rate of CU is high in subgroups of young violent patients with psychotic disorders, little is known about the possible effect of the age of onset of CU on later violent behaviors (VB). So, we aimed to explore the impact of age at onset of CU on the risk of displaying VB in a cohort of early psychosis patients. METHOD: Data were collected prospectively over a 36-month period in the context of an early psychosis cohort study. A total of 265 patients, aged 18-35 years, were included in the study. Logistic regression was performed to assess the link between age of onset of substance use and VB. RESULTS: Among the 265 patients, 72 had displayed VB and 193 had not. While violent patients began using cannabis on average at age 15.29 (0.45), nonviolent patients had started on average at age 16.97 (0.35) (p = 0.004). Early-onset CU (up to age 15) was a risk factor for VB (odds ratio = 4.47, confidence interval [CI]: 1.13-20.06) when the model was adjusted for age group, other types of substance use, being a user or a nonuser and various violence risk factors and covariates. History of violence and early CU (until 15) were the two main risk factors for VB. CONCLUSIONS: Our results suggest that early-onset CU may play a role in the emergence of VB in early psychosis.