Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials-a LYSA and GLA/ DSHNHL collaboration.

Progression or relapse in the central nervous system (CNS) remains a rare but mostly fatal event for patients with diffuse large B-cell lymphoma (DLBCL). In a retrospective analysis of 5189 patients treated within 19 prospective German and French phase 2/3 trials, we identified 159 patients experiencing a CNS event (relapse: 62%, progression: 38%). Intracerebral, meningeal, intraspinal, or combined involvement was reported in 44%, 31%, 3%, and 22% of patients, respectively. 62 of 155 evaluable patients (40%) showed concurrent systemic progression/ relapse. 82% of all CNS events occurred within two years after study inclusion or randomization. 87% of patients showed extranodal involvement outside the CNS. Patients generally had poor outcomes with a median overall survival (OS) of 3.4 months (95% CI 2.9-4.2) and a 2-year OS of 15% (10-22%). Outcomes did not differ depending on the site or time point of CNS events. Patients with isolated CNS events demonstrated significantly better OS (p = 0.023). Twenty-five patients were consolidated with autologous or allogeneic stem cell transplantation and achieved a 3-year OS of 36% (20-66%). This large study including more than 5000 DLBCL patients highlights the unmet medical need to improve the outcome of DLBCL patients suffering from CNS relapse.

Hematopoietic stem cell transplantation for DLBCL: a report from the European Society for Blood and Marrow Transplantation on more than 40,000 patients over 32 years.

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Patient- and family-reported experiences of their treating teams in early psychosis services in Chennai, India and Montreal, Canada.

BACKGROUND: Cross-cultural psychosis research has mostly focused on outcomes, rather than patient and family experiences. Therefore, our aim was to examine differences in patients' and families' experiences of their treating teams in early intervention services for psychosis in Chennai, India [low- and middle-income country] and Montreal, Canada [high-income country]. METHODS: Patients (165 in Chennai, 128 in Montreal) and their families (135 in Chennai, 110 in Montreal) completed Show me you care, a patient- and family-reported experience measure, after Months 3, 12, and 24 in treatment. The measure assesses the extent to which patients and families view treating teams as being supportive. A linear mixed model with longitudinal data from patient and family dyads was used to test the effect of site (Chennai, Montreal), stakeholder (patient, family), and time on Show me you care scores. This was followed by separate linear mixed effect models for patients and families with age and gender, as well as symptom severity and functioning as time-varying covariates. RESULTS: As hypothesized, Chennai patients and families reported more supportive behaviours from their treating teams (ß=4.04; ß= 9, respectively) than did Montreal patients (Intercept =49.6) and families (Intercept=42.45). Higher symptom severity over follow-up was associated with patients reporting lower supportive behaviours from treating teams. Higher levels of positive symptoms (but lower levels of negative symptoms) over follow-up were associated with families reporting lower supportive behaviours from treating teams. There was no effect of time, age, gender and functioning. CONCLUSIONS: The levels to which treating teams are perceived as supportive may reflect culturally shaped attitudes (e.g., warmer attitudes towards healthcare providers in India vis-à-vis Canada) and actual differences in how supportive treating teams are, which too may be culturally shaped. Being expected to be more involved in treatment, Chennai families may receive more attention and support, which may further reinforce their involvement. Across contexts, those who improve over follow-up may see their treating teams more positively.

The impact of Bruton's tyrosine kinase inhibitor treatment on COVID-19 outcomes in Chinese patients with chronic lymphocytic leukemia.

Background: Impact of B-cell depletion following treatment with Bruton tyrosine kinase-inhibitors (BTKi) on the outcome of SARS-CoV-2 infection in chronic lymphocytic leukemia (CLL) patients remain controversial. We investigated the impact of BTKi on susceptibility and the severity of COVID-19 in Chinese patients with CLL during the first wave of COVID-19 (Omicron variant). Methods: CLL patients (n=171) visiting the Institute of Hematology, Peoples' Hospital, China (November 15, 2022- January 20, 2023) were included in the study. Seventeen patients receiving BTKi and venetoclax with or without obinutuzumab were excluded. Data from 117 patients receiving treatment with BTKi were collected using a standardized questionnaire through telephone interviews. Thirty-four patients without CLL-specific treatment served as controls. The data was analysed using IBM SPSS Software version 21 and a P value of <0.05 was considered statistically significant. Results: The median age of patients was 67 years and majority were males (n=100). Treatment with BTKi was not associated with higher incidence of COVID-19 (74% [95% Confidence Interval (CI) 60%, 92%]) versus 74% (CI 48%, 100%) without any treatment (P=0.92). Hypoxemia was reported by 45% (32%, 61%) and 16% (4%, 41%) (P=0.01). BTKi was the only independent risk factor of hypoxemia (Hazard Ratio [HR], 4.22 [1.32, 13.50]; P = 0.02). Five (5.7%) patients with COVID-19 under BTKi required ICU admission; 4 of them died. No ICU admissions/deaths were observed in the control group. Conclusion: In Chinese patients with CLL and treated with BTKi experienced more severe lung disease and ICU admissions due to COVID-19 than patients without CLL therapy. Frequency of infections with SARS-CoV-2, however, was not different in patients with or without BTKi treatment.

Characterization of depression subtypes and their relationships to stressor profiles among middle-aged and older adults: An analysis of the canadian longitudinal study on aging (CLSA).

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors.

A decade of chronic lymphocytic leukaemia therapy in Germany: Real-world treatment patterns and outcomes (2010-2022).

Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010-2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions. The study population included patients with two confirmed CLL diagnoses. Treatment patterns were analysed, and survival outcomes were compared using time-to-event analyses. In the analysed cohort of 2983 incident CLL patients, 1041 started first-line therapy between 2011 and 2022, with a median duration of 18 months from diagnosis to the first prescription. Chemoimmunotherapy, the predominant 1L therapy until 2019, decreased significantly, while targeted therapy usage increased from 3% in 2015 to 77% in 2022. Targeted therapies became dominant in patients receiving treatment for relapsed or refractory disease after 2016. Median treatment durations were: 122 days for chemo, 176 days for chemo-immuno, and 373 days for targeted therapy. The overall survival for patients diagnosed in or after 2016 was significantly better (hazard ratio 0.56, 95% confidence interval, 0.44-0.69)). The adoption of targeted therapies like ibrutinib and venetoclax has transformed CLL treatment in Germany, leading to improved patient outcomes. Additionally, we demonstrate successful adherence to evolving clinical guidelines.

Digital Health Interventions and Patient Safety in Abdominal Surgery: A Systematic Review and Meta-Analysis.

Importance: Over the past 2 decades, several digital technology applications have been used to improve clinical outcomes after abdominal surgery. The extent to which these telemedicine interventions are associated with improved patient safety outcomes has not been assessed in systematic and meta-analytic reviews. Objective: To estimate the implications of telemedicine interventions for complication and readmission rates in a population of patients with abdominal surgery. Data Sources: PubMed, Cochrane Library, and Web of Science databases were queried to identify relevant randomized clinical trials (RCTs) and nonrandomized studies published from inception through February 2023 that compared perioperative telemedicine interventions with conventional care and reported at least 1 patient safety outcome. Study Selection: Two reviewers independently screened the titles and abstracts to exclude irrelevant studies as well as assessed the full-text articles for eligibility. After exclusions, 11 RCTs and 8 cohort studies were included in the systematic review and meta-analysis and 7 were included in the narrative review. Data Extraction and Synthesis: Data were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline and assessed for risk of bias by 2 reviewers. Meta-analytic estimates were obtained in random-effects models. Main Outcomes and Measures: Number of complications, emergency department (ED) visits, and readmissions. Results: A total of 19 studies (11 RCTs and 8 cohort studies) with 10 536 patients were included. The pooled risk ratio (RR) estimates associated with ED visits (RR, 0.78; 95% CI, 0.65-0.94) and readmissions (RR, 0.67; 95% CI, 0.58-0.78) favored the telemedicine group. There was no significant difference in the risk of complications between patients in the telemedicine and conventional care groups (RR, 1.05; 95% CI, 0.77-1.43). Conclusions and Relevance: Findings of this systematic review and meta-analysis suggest that perioperative telehealth interventions are associated with reduced risk of readmissions and ED visits after abdominal surgery. However, the mechanisms of action for specific types of abdominal surgery are still largely unknown and warrant further research.

Childhood maltreatment and the risk of impaired glucose metabolism or type 2 diabetes in young adults: Findings from the Lifelines Cohort Study.

We examined the associations between childhood maltreatment and the risk of impaired glucose metabolism (IGM) or type 2 diabetes (T2D) in young adults aged 18-35. Participants (N = 8506) from the Lifelines Cohort Study without IGM or diabetes at baseline (2007-2013) were included. Childhood maltreatment was assessed by the Childhood Trauma Questionnaire (CTQ) and incident IGM/T2D was assessed by haemoglobin A1c levels (≥5.7%) in 2014-2017. There were 223 (2.6%) cases of IGM/T2D during the follow-up period. After adjusting for sociodemographic and health/lifestyle covariates and follow-up time, only the CTQ Sexual Abuse subscale was significantly associated with IGM/T2D (RR = 1.05 [95% CI = 1.01, 1.10]). The association remained when additionally accounting for depressive and anxiety symptoms (RR = 1.05 [95% CI = 1.00, 1.09]). Childhood sexual abuse was associated with an increased risk of IGM/T2D in young adults, highlighting the long-term metabolic consequences of childhood maltreatment.

Chimeric antigen receptor-T cell therapy shows similar efficacy and toxicity in patients with diffuse large B-cell lymphoma aged 70 and older compared to younger patients: A multicenter cohort study.

CD19-directed chimeric antigen receptor (CAR)-T cell therapy has become a standard treatment for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). While the benefits of CAR-T cell treatment are clear in the general patient population, there remains a relative scarcity of real-world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR-T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR-T infusion (<70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged <70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow-up of 8.3 months, median progression-free survival was 10.2 months (95% confidence interval [CI]: 6.5-21.8) and 11.1 months (95% CI: 4.9-NR) (p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8-NR) and 34.4 months (95% CI: 10.1-NR) (p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome (p = 0.53) or grade ≥3 neurotoxicity (p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR-T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR-T cell therapy should be not withheld for elderly patients with r/r DLBCL.

Patient-reported outcome measures in early psychosis: A cross-cultural, longitudinal examination of the self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada.

OBJECTIVE: Despite their acknowledged value, patient-reported outcome measures (PROMs) are infrequently used in psychosis, particularly in low-and middle-income countries. We compared ratings on two single-item PROMs, Self-Rated Health (SRH) and Self-Rated Mental Health (SRMH), of persons receiving similar early psychosis services in Chennai, India and Montreal, Canada. We hypothesized greater improvements in SRH and SRMH in the Chennai (compared to the Montreal) sample. METHODS: Participants (Chennai N = 159/168 who participated in the larger study; Montreal N = 74/165 who participated in the larger study) completed the SRH and SRMH during at least two out of three timepoints (entry, months 12 and 24). Repeated measures proportional odds logistic regressions examined the effects of time (baseline to month 24), site, and relevant baseline (e.g., gender) and time-varying covariates (i.e., symptoms) on SRH and SRMH scores. RESULTS: SRH (but not SRMH) scores significantly differed between the sites at baseline, with Chennai patients reporting poorer health (OR: 0.33; CI: 0.18, 0.63). While Chennai patients reported similar significant improvements in their SRH (OR: 7.03; CI: 3.13; 15.78) and SRMH (OR: 2.29, CI: 1.03, 5.11) over time, Montreal patients only reported significant improvements in their SRMH. Women in Chennai (but not Montreal) reported lower mental health than men. Higher anxiety and longer durations of untreated psychosis were associated with poorer SRH and SRMH, while negative symptoms were associated with SRH. CONCLUSIONS: As hypothesized, Chennai patients reported greater improvements in health and mental health. The marked differences between health and mental health in Montreal, in contrast to the overlap between the two in Chennai, aligns with previous findings of clearer distinctions between mind and body in Western societies. Cross-context (e.g., anxiety) and context-specific (e.g., gender) factors influence patients' health perceptions. Our results highlight the value of integrating simple PROMs in early psychosis.

Radiotherapy in younger patients with advanced aggressive B-cell lymphoma-long-term results from the phase 3 R-MegaCHOEP trial.

The role of consolidative radiotherapy (RT) for patients with aggressive B-cell lymphoma has not been fully elucidated. The R-MegaCHOEP trial investigated the use of high-dose chemotherapy and rituximab with subsequent autologous stem cell transplantations compared to conventional immunochemotherapy (R-CHOEP) for high-risk patients up to 60 years. The study protocol included RT for patients with bulky (maximum diameter ≥7.5 cm) or extranodal disease. Two-hundred sixty-one patients were analyzed, 120 of whom underwent RT. The most frequently irradiated regions were mediastinum (n = 50) and paraaortic (n = 27). Median RT dose was 36 Gray in median fractions of 1.8 Gray. Acute toxicities were mostly mild to moderate, with only 24 and 8 grade 3 and 4 toxicities reported during RT. Patients with bulky disease who received RT showed significantly better 10-year EFS, PFS and OS (EFS: 64% vs. 35%; p < 0.001; PFS 68% vs. 47%; p = 0.003; OS: 72% vs. 59%; p = 0.011). There was no significant increase in secondary malignancies with the use of RT. RT administered for consolidation of bulky disease after immunochemotherapy improved the prognosis of young high-risk patients with aggressive B-cell lymphoma and should be considered part of first-line therapy. The trial was registered with ClinicalTrials.gov, number NCT00129090.

Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder.

Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.

Oral health-related quality of life and depressive symptoms in adults: longitudinal associations of the English Longitudinal Study of Ageing (ELSA).

BACKGROUND: Little is known about the relationship between oral health status and depressive symptoms in adults in England. The aim of this study was to examine the longitudinal association between oral health parameters and depressive symptoms in adults in England. METHODS: Data were obtained from the English Longitudinal Study of Aging (ELSA), which included information on self-rated oral health, oral impairment in daily life (Oral Impacts on Daily Performances, OIDP), and depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D) in 6790 adults aged ≥ 50 years. Wave 3 data were used as baseline, while Waves 5 and 7 were used for follow-up assessments. Logistic regression was used to determine whether depressive symptoms at baseline anticipated self-rated oral health and OIDP and whether oral health status (at baseline) was associated with the development of depressive symptoms at follow-up assessment. RESULTS: Participants with poor self-rated oral health were at higher risk of developing depressive symptoms, even after adjusting for behavioral, clinical, and sociodemographic characteristics (OR = 1.69, 95% CI 1.38-2.07). Similarly, having oral impacts on daily performances were associated with the development of depressive symptoms: The OR for developing depressive symptoms at Wave 5 or 7 was 2.19 (95% CI 1.62-2.96) after adjustment for all covariates. Participants with depressive symptoms at baseline were more likely to report poor self-rated oral health (OR = 1.93, 95% CI 1.52-2.44) or one or more oral impacts (OR = 1.86, 95% CI 1.45-2.40) at follow-up than those without depressive symptoms at baseline, even after adjusting for confounders. CONCLUSIONS: In the present study, a bidirectional association was found between depressive symptoms and poor oral health in older adults. Maintaining good oral health in older adults may be a protective factor against depressive symptoms. Therefore, more attention should be paid to promoting oral health awareness in older adults, including encouraging regular dental checkups, proper toothbrushing and flossing techniques, and healthy lifestyles.

Ultra-processed foods consumption, depression, and the risk of diabetes complications in the CARTaGENE project: a prospective cohort study in Quebec, Canada.

Introduction: This study aimed to assess the association between depression, ultra-processed food consumption (UPFs), and the risk of developing diabetes-specific complications in adults with type 2 diabetes (T2D). Methods: Baseline data came from the CARTaGENE study, a health survey of adults (40-69 years) in Quebec, Canada. The incidence of T2D complications was examined in N= 683 participants with T2D without complications at baseline by linking survey data with administrative health data. Food and drink consumption was assessed using the Canadian Diet History Questionnaire and categorized by NOVA classification. Participants were categorized into tertiles of UPFs consumption. Depression was defined as having elevated depressive symptoms based on the Patient Health Questionnaire-9 or the use of antidepressant medications. Cox regression models were used to estimate the associations between UPFs, depression, and T2D complications. Results: In total, 105 individuals developed diabetes-related complications over a 7-year period. Participants with high depressive symptoms and high UPFs consumption had the highest risk for diabetes complications (adjusted hazard ratio (aHR) 2.07, 95% CI: 0.91 - 4.70), compared to participants with low depressive symptoms and low UPFs consumption. Higher risks for diabetes complications were observed when high depressive symptoms and antidepressant use were combined with high UPFs consumption (aHR 2.59, 95% CI: 1.32 - 5.06). Conclusion: This study indicates that those with co-occurring depression and high UPFs consumption have a greater risk of diabetes complications. Early management and monitoring of both risk factors might be essential to prevent diabetes complications.