Efficacy of CAR T-Cell Therapy is Not Impaired by Previous Bispecific Antibody Treatment in Large B-Cell Lymphoma.

In this retrospective study, CAR T-cells remained effective in relapsed/refractory LBCL patients after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.

Nivolumab combined with brentuximab vedotin with or without mediastinal radiotherapy for relapsed/refractory primary mediastinal large B-cell lymphoma.

Not available.

Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.

Long-term excess mortality and net survival among elderly diffuse large B-cell lymphoma patients after front-line R-CHOP treatment.

In the era of immunochemotherapy, data on the long-term prognosis of elderly patients diagnosed with a diffuse large B-cell lymphoma (DLBCL) are scarce. In this population and on the longer term, other-cause mortality is an important competing risk that needs to be accounted for. Using clinical trial data and relative survival approaches, we estimated the 10-year net survival (NS) and we described the excess mortality hazard (EMH) due (directly or indirectly) to the DLBCL, over time and according to main prognosis factors using flexible regression modelling. The 10-year NS was 65% [59; 71]. Using the flexible modelling, we showed that the EMH decreases steeply after diagnosis. The variables 'performance status', 'number of extra-nodal sites' and the serum 'lactate dehydrogenase' were strongly associated with the EMH, even after adjustment on other important variables. EMH is very close to zero at 10 years for the whole population, so DLBCL patients do not experience an increased mortality compared to the general population in the long term. The number of extra-nodal sites was an important prognostic factor shortly after diagnosis, suggesting that it is correlated with an important but unmeasured prognostic factor that would lead to this selection effect over time.

Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B-cell lymphoma: results of a multicentric prospective cohort study.

This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score.Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03-89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor.

Cerebral Metabolic Signature of Chronic Benzodiazepine Use in Nondemented Older Adults: An FDG-PET Study in the MEMENTO Cohort.

OBJECTIVE: We sought to examine the association between chronic Benzodiazepine (BZD) use and brain metabolism obtained from 2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in the MEMENTO clinical cohort of nondemented older adults with an isolated memory complaint or mild cognitive impairment at baseline. METHODS: Our analysis focused on 3 levels: (1) the global mean brain standardized uptake value (SUVR), (2) the Alzheimer's disease (AD)-specific regions of interest (ROIs), and (3) the ratio of total SUVR on the brain and different anatomical ROIs. Cerebral metabolism was obtained from 2-deoxy-2-fluoro-D-glucose-FDG-PET and compared between chronic BZD users and nonusers using multiple linear regressions adjusted for age, sex, education, APOE ε 4 copy number, cognitive and neuropsychiatric assessments, history of major depressive episodes and antidepressant use. RESULTS: We found that the SUVR was significantly higher in chronic BZD users (n = 192) than in nonusers (n = 1,122) in the whole brain (beta = 0.03; p = 0.038) and in the right amygdala (beta = 0.32; p = 0.012). Trends were observed for the half-lives of BZDs (short- and long-acting BZDs) (p = 0.051) and Z-drug hypnotic treatments (p = 0.060) on the SUVR of the right amygdala. We found no significant association in the other ROIs. CONCLUSION: Our study is the first to find a greater global metabolism in chronic BZD users and a specific greater metabolism in the right amygdala. Because the acute administration of BZDs tends to reduce brain metabolism, these findings may correspond to a compensatory mechanism while the brain adapts with global metabolism upregulation, with a specific focus on the right amygdala.

Correlation between assessment of cytochrome P450 1A2 activity and enzyme activity scores, and their relation to clozapine exposure.

AIMS: Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of antipsychotic drugs such as clozapine and olanzapine. Personalization of these treatments requires an accurate estimation of CYP1A2 activity. In this study, we aimed (1) to evaluate the correlation between activity score (AS), covariate-corrected activity score (CCS) and the phenotype of CYP1A2 using a caffeine test probe and (2) to investigate their relationship with dose-adjusted clozapine concentrations in a subgroup of the cohort. METHODS: A multicentric, retrospective and observational study was carried out in the French university hospitals of Marseille and Tours. CYP1A2 activity was calculated by the paraxanthine/caffeine (17X/137X) ratio determined 4 h after an oral intake of 100 mg caffeine. AS was calculated according to the CYP1A2*1F alleles. CCS was calculated according to the CYP1A2*1F alleles, smoking status and the presence of concomitant inhibitors. RESULTS: As expected, among the 89 patients included, the 17X/137X ratio was significantly higher in patients who smoked. We found a significant but modest correlation between the 17X/137X ratio and CCS (R2 = 0.3, P = 1.74 × 10-8 ) but none between the 17X/137X ratio and AS (R2 = -0.007, P = 0.52). AS was not correlated with dose-adjusted clozapine levels, contrary to CCS (R2 = 0.19, P = 0.016) and especially the 17X/137X ratio (R2 = 0.42, P = 1.7 × 10-5 ). CONCLUSIONS: Correlation with clozapine concentrations showed the advantage of the 17X/137X ratio over the CCS in clozapine dose optimization. CYP1A2 activity, especially when determined by the caffeine probe, may be used to personalize clozapine dosing for patients experiencing treatment failure.

Clinical features and prognostic factors of Magnusiomyces (Saprochaete) infections in haematology. A multicentre study of SEIFEM/Fungiscope.

BACKGROUND: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies. METHODS: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia. RESULTS: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2-78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p < .0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p = .001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396-5.204, p = .003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151-4.376, p = .018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102-7.601, p < .001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192-5.222, p = .015). CONCLUSIONS: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome.

Kidney Transplant T Cell-Mediated Rejection Occurring After Anti-CD19 CAR T-Cell Therapy for Refractory Aggressive Burkitt-like Lymphoma With 11q Aberration: A Case Report.

Post-transplant lymphoproliferative disorder is a growing complication of kidney transplantation and is associated with a poor prognosis. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an important new treatment option modifying the outcome of refractory hematological cancers. Here, we report the case of a 40-year-old kidney transplant recipient who developed a Burkitt-like lymphoma with 11q aberration 5 years after transplantation. After 3 unsuccessful lines of chemotherapy, it was decided to treat the patient with anti-CD19 CAR T cells as a salvage therapy. Three months after CAR T-cell infusion, she experienced a grade IIB T cell-mediated rejection with severe tubulitis (T3), slight interstitial inflammation (I1), and severe intimal arteritis (V2) with blood suffusion. Among T cells infiltrating the graft, some of them expressed the anti-CD19 CAR. CAR T cells within the graft and in blood samples were also detected by droplet digital polymerase chain reaction. Function of the kidney transplant improved after corticosteroid treatment and remained stable. However, lymphoma progressed, with a massive pulmonary mass leading to the patient's death 10 months after CAR T-cell infusion.

Retrospective analysis of the safety of peripherally inserted catheters versus implanted port catheters during first-line treatment for patients with diffuse large B-cell lymphoma.

OBJECTIVES: Both peripherally inserted central catheters (PICCs) and implanted port catheters (PORTs) are commonly used for the delivery of immunochemotherapy. We compared the safety of the two types of devices in a homogeneous and monocentric population of diffuse large B-cell lymphoma (DLBCL) patients who were treated with first-line immunochemotherapy by evaluating the numbers of catheter-related venous thromboses (VTs) and infections that occurred in the six months after implantation according to the type of device. METHODS: Using a propensity score, the adjusted relative risk (ARR) between the type of catheter and the occurrence of catheter-related complications (infection and/or VT) of interest was retrospectively determined. RESULTS: 479 patients were enrolled (266 PORTs/213 PICCs), and 26 VTs (5.4%) and 30 infections (6.3%) were identified in the period following PICC/PORT implantation. The adjusted relative risk (ARR) of catheter-related complications (infection and/or VT) according to the type of device was 2.6 (95% CI =1.3-5.9, p = .0075). This risk increase associated with the PICC device was significant for both infections (ARR = 3.2; 95% CI = 1.3-10.9) and thrombosis (ARR = 4; 95% CI = 1.5-11.6). CONCLUSION: Our study supports the preferential use of PORTs for the first line of treatment for DLBCL patients.

The Role of Telemedicine in the Management of the Behavioral and Psychological Symptoms of Dementia: A Systematic Review.

The first-line management of behavioral and psychological symptoms of dementia (BPSD) is based on nonpharmacologic interventions such as the provision of guidance and medical support to caregivers. However, accessibility to specialized care and medical resources is often scarce. The ongoing COVID-19 pandemic has compromised the delivery of outpatient care (notably in order to minimize the risk of disease transmission), thus making it essential to provide other means of accessing care for these patient populations. The use of telemedicine (TM) may be a means of increasing access to specialist care for patients with disabilities and poor access to health services, such as those with BPSD. The aim of this study is to provide a review of the literature on the use of TM for treatment and follow-up of patients with BPSD and their caregivers. We searched the PUBMED, EMBASE and CINAHL for articles published between January 1st, 2000, and December 31st, 2020, on the applicability of TM support for people with BPSD and their caregivers. We included open-label studies, qualitative studies, and randomized controlled trials . We did not include studies on the use of TM during the COVID-19 pandemic. A total of 22 publications were included and reviewed. TM was found to 1) be acceptable and feasible for both patients and caregivers, 2) decrease the frequency and intensity of BPSD, and 3) improve the caregiver's perceived wellbeing and mental health. Videoconferencing was effective for patient-centered interventions in nursing homes. Telephone-based interventions were more relevant when they were targeted at caregivers. The published studies are lacking in scope and high-quality studies are now needed to confirm these findings and assess TM's cost-effectiveness and ability to improve the management of patients with BPSD. In view of the ongoing COVID-19 pandemic, remote solutions for assessing and monitoring individuals with BPSD are urgently needed - particularly those living in rural areas and so-called "medical deserts."

Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study.

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting.Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined.Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured.Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

Comparison of bone marrow trephine sample quality between a drill-powered system and a manual needle system.

CONTEXT: Bone marrow biopsy (BMB) is a common procedure in haematology used for the diagnosis and evaluation of response treatment. Because the procedure is difficult for haematologists to perform, patients often experience pain and stress. On Control, a system device, was introduced in the 2000s and uses a drill-powered needle to perform BMB. OBJECTIVE: The aim of this study was to compare the quality of BMB, based on the length of the trephine, the number of interosseous spaces and the interpretability of the examination, obtained from manual BMB vs. drill-powered BMB. The secondary objectives were to evaluate the patient's pain and anxiety, and the haematologist's perceived difficulty in performing BMB. DESIGN: This was a retrospective study conducted between June 2016 and June 2017 in the Henri Becquerel Cancer Centre in Rouen, France. RESULTS: A total of 439 patients were included in the study; the sex ratio (M:F) was 1.34 and 70.2% underwent a drill-powered BMB. A significant difference was observed concerning trephine length (14.30 ± 5.58 mm with the drill-powered system vs. 11.18 ± 4.43 mm with manual BMB, p < 0.0001) and the number of interosseous spaces (9.49 ± 5.35 vs. 7.93 ± 4.01, respectively, p = 0.01). The interpretability of the examination did not differ between the two procedures (p = 0.9). CONCLUSIONS: On Control, the drill-powered system for BMB, is widely distributed in North America and Europe, but this procedure is not yet generally applied. Although this procedure is costly, the ongoing development of this technique, because of its performance, is beneficial especially to obese patients.

Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.

INTRODUCTION: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis. METHODS: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aß)1-42 , Aß1-40 , Aß1-42 /Aß1-40 ratio were analyzed with logistic and Cox models. RESULTS: Converters to dementia had lower level of plasma Aß1-42 (37.1 pg/mL [12.5] vs. 39.2 [11.1] , P value = .03) and lower Aß1-42 /Aß1-40 ratio than non-converters (0.148 [0.125] vs. 0.154 [0.076], P value = .02). MCI participants in the highest quartile of Aß1-42 /Aß1-40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E ε4, hippocampus atrophy = 0.52 (95% confidence interval [0.31-0.86], P value = .01). DISCUSSION: In this large cohort of MCI subjects we identified a threshold for plasma Aß1-42 /Aß1-40 ratio that may detect patients with a low risk of conversion to dementia within 3 years.

Neuroinflammation and depression: A review.

Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor that interacts with the three neurobiological correlates of major depressive disorder: depletion of brain serotonin, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and alteration of the continuous production of adult-generated neurons in the dentate gyrus of the hippocampus. This review discusses the main players in brain immunity as well as how inflammation interacts with the above three mechanisms. It is reported that kynurenine (KYN) pathway alteration in favour of its excitotoxic component and HPA axis dysregulation have the common effect of increasing extracellular glutamate levels and glutamate neurotransmission, which can impact hippocampal neurogenesis. This pathophysiological cascade appears to be triggered or sustained and reinforced by any chronic inflammatory condition involving increased circulating markers of inflammation that are able to cross the blood-brain barrier and activate microglia; it can also be the consequence of primary brain neuroinflammation, such as in neurodegenerative disorders with early manifestations that are frequently depressive symptoms. Further recent data indicate that primary microglial activation may also result from a direct impact of chronic stress on vascular function. The intricated dynamic crosstalk between neuroinflammation and other relevant neurobiological correlates of depression add to evidence that neuroinflammation may be a key therapeutic target for future therapeutic strategies in major depressive disorder.

Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study.

The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients] were assessed in this non-interventional study. Median age of the patients was 33.5 years (range 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype are correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, NA=6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). Mean of DeltaSUVmax after C2 was -78.8%. We analyzed ctDNA after C2 for 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.

Brain immune cells characterization in UCMS exposed P2X7 knock-out mouse.

BACKGROUND: Several lines of evidence suggest that neuroinflammation might be a key neurobiological mechanism of depression. In particular, the P2X7 receptor (P2X7R), an ATP-gated ion channel involved in activation of the pro-inflammatory interleukin IL-1ß, has been shown to be a potential new pharmacological target in depression. The aim of this study was to explore the impact of unpredictable chronic mild stress (UCMS) on behavioural changes, hippocampal neurogenesis, and cellular characterisation of brain immune cells, in P2X7R Knock-Out (KO) mice. METHODS: P2X7R KO and wild-type (WT) mice were subjected to a 6-week UCMS protocol and received a conventional oral antidepressant (15 mg.kg-1 fluoxetine) or water per os. The mice then underwent behavioural tests consisting of the tail suspension test (TST), the elevated plus maze (EPM) test, the open field test, the splash test and the nest building test (week 7). Doublecortin immunostaining (DCX) of brain slices was used to assess neurogenesis in the dentate gyrus. Iba1 and TMEM119 immunostaining was used to characterise brain immune cells, Iba1 as a macrophage marker (including microglial cells) and TMEM119 as a potential specific resident microglial cells marker. RESULTS: After a 6-week UCMS exposure, P2X7R KO mice exhibited less deterioration of their coat state, spent a significantly smaller amount of time immobile in the TST and spent a larger amount of time in the open arms of the EPM. As expected, adult ventral hippocampal neurogenesis was significantly decreased by UCMS in WT mice, while P2X7R KO mice maintained ventral hippocampal neurogenesis at similar levels in both control and UCMS conditions. In stress-related brain regions, P2X7R KO mice also exhibited less recruitment of Iba1+/TMEM119+ and Iba1+/TMEM119- cells in the brain. The ratio between these two staining patterns revealed that brain immune cells were mostly composed of Iba1+/TMEM119+ cells (87 to 99%), and this ratio was affected neither by P2X7R genetic depletion nor by antidepressant treatment. DISCUSSION: Behavioural patterns, neurogenesis levels and density of brain immune cells in P2X7R KO mice after exposure to UCMS significantly differed from control conditions. Brain immune cells were mostly increased in brain regions known to be sensitive to UCMS exposure in WT but not in P2X7R KO mice. Considering Iba1+/TMEM119- staining might characterize peripheral immune cells, the ratio between Iba1+/TMEM119+ cells and IBA1+/TMEM119- cells, suggests that the rate of peripheral immune cells recruitment may not be modified neither by P2X7R gene expression nor by antidepressant treatment.

Outcomes after intensive care unit admission in newly diagnosed diffuse large B-cell lymphoma patients: A real-life study.

We conducted a retrospective study to analyze the prognostic factors impacting the overall survival (OS) and progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) patients undergoing first-line therapy and admitted to intensive care unit (ICU) compared to a control cohort who did not required ICU admission. Between January 1, 2008, and December 31, 2018, 828 patients were diagnosed with DLBCL at our institution, including 72 patients who were required ICU admission during disease course. Among them, forty-five patients undergoing homogeneous first-line therapy with /R-CHOP-like regimen and ICU-admitted were selected for the present analysis. Control "non-ICU" DLBCL patients were matched by age, IPI score and treatment received. The median age at ICU admission was 65 years, 97.8% of patients displayed advanced-stage disease (III/IV), and 84.4% had a high IPI score (3-5). The main reasons for ICU admission were acute respiratory failure (40.0%) and septic shock (33.3%). The ICU mortality rate was 33.3%. The 2-year PFS was lower in ICU survivors patients than in non-ICU patients: 31.7% (95% CI 18.5-54.1) vs 60.8% (95% CI 51.2-72.1, P = .00049). Admission to the ICU is an event that clearly impacts the outcomes of patients with DLBCL, until 2 years after the event. ICU prognosis seems mainly related to critical patient severity at admission rather than lymphoma-related prognostic factors (IPIs), suggesting that ICU admission criteria should not be based only on the lymphoma prognosis.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma.

Refractory/relapsed diffuse large B-cell lymphoma remains a major unmet medical need with poor outcome, especially for patients considered ineligible for stem cell transplant. Polatuzumab vedotin (PV) is a first-in-class anti-CD79b antibody-drug conjugate that contains the microtubule inhibitor monomethyl auristatin E. The development of PV is currently very active. This drug was US FDA approved in 2019 in combination with bendamustine and rituximab for the treatment of refractory/relapsed diffuse large B-cell lymphoma in third line and more, after demonstrating relevant efficacy and acceptable safety in a pivotal randomized Phase II trial. This review summarizes the features of this new drug with the primary focus on the clinical work supporting efficacy, relevance and tolerability of PV.