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The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/– interferon). [ABSTRACT FROM AUTHOR]

Background: Alcohol misuse is common and causes substantial harm. Internet-delivered cognitive behaviour therapy (ICBT) is effective in reducing alcohol misuse; however, the literature investigating how treatment outcomes are impacted by patients' preferences for therapist- versus self-guided ICBT for alcohol misuse is sparse., Methods: In this preference trial, 74 eligible patients (who reported ≥ 14 drinks in the previous week and obtained scores suggesting hazardous or harmful drinking) chose between enrolling in either therapist- or self-guided ICBT for alcohol misuse. We investigated whether those who chose therapist- versus self-guided ICBT differed in their (a) drinking outcomes-as measured by Timeline Follow-Back (TLFB) and heavy drinking days (HDD) at post-treatment and 3-month follow-up-and (b) post-treatment ICBT engagement and satisfaction., Results: The majority (81.1%) of eligible patients chose therapist-guided ICBT. These patients reported higher psychotropic medication use, drinking difficulties, and anxiety symptoms. For both the therapist- and self-guided patients, a modified intention-to-treat analysis revealed large within-group treatment effects for TLFB (β =  - 2.64, SE 0.66; p < 0.001) and HDD (β =  - 0.34, SE 0.07; p < 0.001), with large pre-to-post-treatment Cohen's effect sizes of d = 0.97 (95% CI [0.49, 1.45]) for TLFB and d = 1.19 (95% CI [0.69, 1.68]) for HDD. The interaction comparing the effects of therapist- to self-guided ICBT over time was not significant for TLFB (p = 0.34) or HDD (p = 0.06). With treatment, for both therapist- and self-guided patients, there was a significant improvement in drinking difficulties, cravings, and confidence with controlling cravings, as well as in anxiety, depression, and functional impairment. Further, the majority (75.7%) of patients completed five or more lessons, as well as reported overall satisfaction with the treatment (88.9%) and increased confidence in managing their symptoms (86.7%); these outcomes also did not differ between therapist- and self-guided patients., Conclusions: The current study shows that ICBT for alcohol misuse is associated with reduced drinking and comorbid mental health difficulties over time, irrespective of whether patients chose to complete the course on their own or with therapist guidance., Trial Registration Number: NCT04611854 ( https://clinicaltrials.gov/ct2/show/NCT04611854 )., (© 2024. The Author(s).)

The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.

Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components., Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned., Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group., (© 2024. The Author(s).)

Background: The continual development and implementation of effective digital interventions is one important strategy that may serve to bridge the well-known treatment gap related to problematic alcohol use. Research suggests that clinician guidance, provided in different ways during the digital intervention (i.e., written weekly messages, phone calls etc.), can boost intervention engagement and effects. Digital psychological self-care (DPSC) is a new delivery format wherein an unguided digital intervention is provided within the framework of a structured care process that includes initial clinical assessment and follow-up interviews. In a recent feasibility study, a DPSC intervention for problematic alcohol use, ALVA, provided without any extra guidance, was found safe and credible and to have promising within-group effects on alcohol consumption. The aim of the current study is to gather information on the effects and efficiency of different forms of guidance added to ALVA, in order to optimize the intervention., Methods: This protocol describes a randomized factorial trial where the effects of two different ways of providing guidance (mid-treatment interview, weekly written messages, respectively) in DPSC for problematic alcohol use are investigated. Optimization criteria will be applied to the results regarding how effective the intervention is at reducing alcohol consumption measured by the number of standard drinks per week together with the clinician time spent on guidance., Discussion: This study will investigate the added benefit of different forms of guidance to DPSC for problematic alcohol use. These added effects will be compared to the added cost of guidance, according to pre-defined optimization criteria., Trial Registration: Clinicaltrials.gov: NCT05649982. Registered on 06 December 2022. Prospectively registered., (© 2024. The Author(s).)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.

Introduction: Therapist-guided internet interventions are often more efficacious than unguided ones. However, the guidance itself requires clinician time, and some research suggests that self-guided interventions could potentially be equally effective. The concept of digital psychological self-care, self-guided internet interventions based on the use of digital tools and provided within a structured clinical process, is presented., Methods: Three new self-care interventions, a sleep diary-based intervention for insomnia, an alcohol diary-based intervention for problematic alcohol use and an intervention with exposure and mindfulness tools for atopic dermatitis (eczema), were developed. Newly developed digital self-care interventions were compared to the earlier therapist-guided interventions they were based on, using published results from three feasibility trials (n's = 30, 36 and 21) and three randomized trials (n's = 148, 166 and 102). The comparison included type of content, duration, length of written material and within-group effect-sizes., Results: In comparison to the guided interventions, clinician time was greatly reduced and the new interventions involved much less reading for participants. The digital self-care tools also showed within-group effect sizes and response rates on par with the more comprehensive guided internet interventions., Discussion: Preliminary results suggest that some guided internet interventions can be transformed into self-guided digital tools. These three examples show that digital psychological self-care, if provided with telephone interviews before and after the intervention, can be viable alternatives to more comprehensive guided internet interventions. Although these examples are promising, further studies, including randomized experiments, are needed to compare treatment efficacies, and to identify which groups of patients may need more comprehensive guided internet interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Alcohol Use Disorders (AUD) are widespread and have serious consequences, but are among the most undertreated mental disorders. Internet interventions have been found effective in treating AUD, but we know little about long-term outcomes, two years or more after treatment. This study explored 12- and 24-month outcomes in alcohol consumption following initial 6-month improvements after a therapist-guided high-intensity internet intervention and an unguided low-intensity internet intervention among individuals with alcohol use disorder. Between-group comparisons were analyzed, as well as within-group comparisons with (1) pre-treatment measurements (2) post-treatment measurements. Participants consisted of a general population sample of internet help-seekers in Sweden. A total of 143 adults (47% men) with a score of 14 (women)/16 (men) or more on the Alcohol Use Disorders Identification Test, alcohol consumption of 11 (women)/14 (men) or more standard drinks the preceding week and ≥ 2 DSM-5 alcohol use disorder (AUD) criteria based on a diagnostic interview were included. The high- and low-intensity internet interventions ( n  = 72 and n  = 71 respectively) consisted of modules based on relapse prevention and cognitive-behavioral therapy. The primary outcome was self-reported alcohol consumption in the preceding week measured as (1) number of standard drinks and (2) number of heavy drinking days. Attrition from self-reported questionnaires was 36% at the 12-month follow-up and 53% at the 24-month follow-up. No significant between-group differences occurred in outcomes at either long-term follow-up. Regarding within-group differences, compared to pre-treatment, alcohol consumption was lower in both high- and low-intensity interventions at both long-term follow-ups [within-group standard drinks effect sizes varied between g  = 0.38-1.04 and heavy drinking days effect sizes varied between g  = 0.65-0.94]. Compared to post-treatment, within-group alcohol consumption in the high intensity intervention increased at both follow-ups; for the low-intensity intervention, within-group consumption decreased at 12-month follow-up, but did not differ compared to post-treatment at 24 months. Both high- and low-intensity internet interventions for AUD were thus associated with overall reductions in alcohol consumption at long term follow-ups, with no significant differences between the two. However, conclusions are hampered by differential and non-differential attrition., Competing Interests: NE is co-founder of the mental well-being application Remente., (© 2023 The Authors.)

Background: Digital interventions based on cognitive-behavioural therapy and relapse prevention can increase treatment access for people with problematic alcohol use, but for these interventions to be cost-effective, clinician workload needs to remain low while ensuring patient adherence and effects. Digital psychological self-care is the provision of a self-guided digital intervention within a structured care process., Aims: To investigate the feasibility and preliminary effects of digital psychological self-care for reducing alcohol consumption., Method: Thirty-six adults with problematic alcohol use received digital psychological self-care during 8 weeks, including telephone assessments as well as filling out self-rated questionnaires, before, directly after and 3 months after the intervention. Intervention adherence, usefulness, credibility and use of clinician time were assessed, along with preliminary effects on alcohol consumption. The study was prospectively registered as a clinical trial (NCT05037630)., Results: Most participants used the intervention daily or several times a week. The digital intervention was regarded as credible and useful, and there were no reported adverse effects. Around 1 h of clinician time per participant was spent on telephone assessments. At the 3-month follow-up, preliminary within-group effects on alcohol consumption were moderate (standardised drinks per week, Hedge's g = 0.70, 95% CI = 0.19-1.21; heavy drinking days, Hedge's g = 0.60, 95% CI = 0.09-1.11), reflecting a decrease from 23 to 13 drinks per week on average., Conclusions: Digital psychological self-care for reducing alcohol consumption appears both feasible and preliminarily effective and should be further optimised and studied in larger trials.

Background: Problematic alcohol use is common among clients seeking transdiagnostic internet-delivered cognitive behavioral therapy (ICBT) for depression or anxiety but is not often addressed in these treatment programs. The benefits of offering clients a psychoeducational resource focused on alcohol use during ICBT for depression or anxiety are unknown., Objective: This observational study aimed to elucidate the impacts of addressing comorbid alcohol use in ICBT for depression and anxiety., Methods: All patients (N=1333) who started an 8-week transdiagnostic ICBT course for depression and anxiety received access to a resource containing information, worksheets, and strategies for reducing alcohol use, including psychoeducation, reasons for change, identifying risk situations, goal setting, replacing drinking with positive activities, and information on relapse prevention. We assessed clients' use and perceptions of the resource; client characteristics associated with reviewing the resource; and whether reviewing the resource was associated with decreases in clients' alcohol use, depression, and anxiety at posttreatment and 3-month follow-up among clients dichotomized into low-risk and hazardous drinking categories based on pretreatment Alcohol Use Disorders Identification Test (AUDIT) scores., Results: During the 8-week course, 10.8% (144/1333) of clients reviewed the resource, and those who reviewed the resource provided positive feedback (eg, 127/144, 88.2% of resource reviewers found it worth their time). Furthermore, 18.15% (242/1333) of clients exhibited hazardous drinking, with 14.9% (36/242) of these clients reviewing the resources. Compared with nonreviewers, resource reviewers were typically older (P=.004) and separated, divorced, or widowed (P<.001). Reviewers also consumed more weekly drinks (P<.001), scored higher on the AUDIT (P<.001), and were more likely to exhibit hazardous drinking (P<.001). Regardless of their drinking level (ie, low risk vs hazardous), all clients showed a reduction in AUDIT-Consumption scores (P=.004), depression (P<.001), and anxiety (P<.001) over time; in contrast, there was no change in clients' drinks per week over time (P=.81). Reviewing alcohol resources did not predict changes in AUDIT-Consumption scores or drinks per week., Conclusions: Overall, ICBT appeared to be associated with a reduction in alcohol consumption scores, but this reduction was not greater among alcohol resource reviewers. Although there was some evidence that the resource was more likely to be used by clients with greater alcohol-related difficulties, the results suggest that further attention should be given to ensuring that those who could benefit from the resource review it to adequately assess the benefits of the resource., (©Vanessa Peynenburg, Ram P Sapkota, Tristen Lozinski, Christopher Sundström, Andrew Wilhelms, Nickolai Titov, Blake Dear, Heather Hadjistavropoulos. Originally published in JMIR Mental Health (https://mental.jmir.org), 18.04.2023.)

Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients., (© 2022. The Author(s).)

Background and Aims: Problem gambling and tobacco use are highly comorbid among adults. However, there are few treatment frameworks that target both gambling and tobacco use simultaneously (i.e., an integrated approach), while also being accessible and evidence-based. The aim of this two-arm open label RCT was to examine the efficacy of an integrated online treatment for problem gambling and tobacco use., Methods: A sample of 209 participants (Mage = 37.66, SD = 13.81; 62.2% female) from North America were randomized into one of two treatment conditions (integrated [n = 91] or gambling only [n = 118]) that lasted for eight weeks and consisted of seven online modules. Participants completed assessments at baseline, after treatment completion, and at 24-week follow-up., Results: While a priori planned generalized linear mixed models showed no condition differences on primary (gambling days, money spent, time spent) and secondary outcomes, both conditions did appear to significantly reduce problem gambling and smoking behaviours over time. Post hoc analyses showed that reductions in smoking and gambling craving were correlated with reductions in days spent gambling, as well as with gambling disorder symptoms. Relatively high (versus low) nicotine replacement therapy use was associated with greater reductions in gambling behaviours in the integrated treatment condition., Discussion and Conclusions: While our open label RCT does not support a clear benefit of integrated treatment, findings suggest that changes in smoking and gambling were correlated over time, regardless of treatment condition, suggesting that more research on mechanisms of smoking outcomes in the context of gambling treatment may be relevant.

The expression patterns of IDO1 and PD-L2 have not been thoroughly investigated in benign lymphadenopathies. The aim with this study was to elucidate how IDO1 and PD-L2 are expressed in benign lymphadenopathies in patients with autoimmune diseases (AD) compared to patients without AD. Formalin-fixed paraffin-embedded lymph nodes from 22 patients with AD and 57 patients without AD were immunohistochemically stained to detect IDO1 and PD-L2. The material was previously stained with EBER in situ hybridization to detect cells harboring the Epstein-Barr virus (EBV). IDO1 and PD-L2 were generally expressed by leukocytes to low degrees, while follicular IDO1+ cells were very rare. IDO1+ cells in single germinal centers were detected in five patients, and there was a high co-occurrence of follicular EBV+ cells in these cases (three of five patients). There were also significant correlations between interfollicular EBV+ cells and interfollicular IDO1+ cells (Spearman rho = 0.32, p = 0.004) and follicular IDO1+ cells (Spearman rho = 0.34, p = 0.004). High or low amounts of IDO1+ or PD-L2+ cells were not statistically significantly associated with patients with AD. However, the lymphadenopathy with the highest amount of interfollicular IDO1+ cells, which was also the only lymphadenopathy in which endothelial cells expressed IDO1, was in a patient with sarcoidosis. This study further supports that the EBV induces the expression of IDO1 and our findings should be recognized by future studies on IDO1 and PD-L2 in inflammatory and malignant conditions.

Introduction: Internet interventions for alcohol problems are effective, but not all participants are helped. Further, the importance of adherence has often been neglected in research on internet interventions for alcohol problems. Prediction analysis can help in prospectively assessing participants' probability of success, and ideally, this information could be used to tailor internet interventions to individual needs., Methods: Data were obtained from a randomized controlled trial on internet interventions for alcohol use disorders. Twenty-nine candidate predictors were run in univariate logistic regressions with two dichotomous dependent outcomes: adherence (defined as completing at least 60% of the treatment modules) and low-risk drinking (defined as drinking within national public health guidelines) at two time points - immediately post-treatment and at the 6-month follow-up. Significant predictors were entered hierarchically into domain-specific logistic regressions. In the final models, predictors still showing significant effects were run in multiple logistic regressions., Results: One predictor significantly predicted adherence: treatment credibility (as in how logical the treatment is and how successful one perceives the treatment to be) assessed during the third week of the intervention. Four predictors significantly predicted low-risk drinking at the post-treatment follow-up: pre-treatment abstinence (i.e., not drinking during the 7 days before treatment started), being of the male gender, and two personality factors - a low degree of antagonism and a high degree of alexithymia. At the 6-month follow-up, pre-treatment abstinence was the only significant predictor., Conclusion: Adherence was not predictive of low-risk drinking. Personality variables may have predictive value and should be studied further. Those who abstain from alcohol during the week before treatment starts have a higher likelihood of achieving low-risk drinking than people who initially continue drinking., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Internet-delivered cognitive behavioral therapy (ICBT) for alcohol misuse has potential to radically improve access to evidence-based care, and there is a need to investigate ways to optimize its delivery in clinical settings. Guidance from a clinician has previously been shown to improve drinking outcomes in ICBT, and some studies suggest that pre-treatment assessments may contribute in initiating early change. The objective of this study was to investigate the added and combined effects of a pre-treatment assessment interview and guidance on the outcomes of ICBT for alcohol misuse delivered in an online therapy clinic., Methods: A 2X2 factorial randomized controlled trial was conducted where participants received access to an 8-week ICBT program, and either a pre-treatment assessment interview (Factor 1), guidance (Factor 2), a combination of these, or neither of these. Participants were 270 individuals (66.8% female, mean age = 46.5) scoring 8 or more on the Alcohol Use Disorders Identification Test and consuming 14 standard drinks or more in the preceding week. Primary outcomes were number of drinks consumed and number of heavy drinking days during the preceding week, 3 months post-treatment., Results: Large within-group effects were found in terms of alcohol reductions (d w  ≥ 0.82, p < 0.001), but neither of the factors significantly improved drinking outcomes. Guidance was associated with greater adherence (i.e. completed modules)., Conclusions: Neither a pre-treatment assessment interview nor guidance from a clinician appears to improve drinking outcomes resulting from internet-delivered cognitive behaviour therapy for alcohol misuse when delivered in a routine online therapy clinic., Trial Registration: NCT03984786. Registered 13 June 2019, https://clinicaltrials.gov/ct2/show/NCT03984786., (© 2022. The Author(s).)

BCOR is a component of a variant Polycomb repressive complex 1 (PRC1.1). PRC1 and PRC2 complexes together constitute a major gene regulatory system critical for appropriate cellular differentiation. The gene is upregulated in germinal center (GC) B cells and mutated in a number of hematologic malignancies. We report BCOR inactivating alterations in 4/7 classic Hodgkin lymphoma (cHL) cell lines, subclonal somatic mutations in Hodgkin and Reed-Sternberg (HRS) cells of 4/10 cHL cases, and deletions in HRS cells of 7/17 primary cHL cases. In mice, conditional loss of Bcor driven by AID-Cre in GC B cells resulted in gene expression changes of 46 genes (>2-fold) including upregulated Lef1 that encodes a transcription factor responsible for establishing T-cell identity and Il9r (interleukin-9 receptor), an important member of the cytokine network in cHL. Our findings suggest a role for BCOR loss in cHL pathogenesis and GC-B cell homeostasis.

Current research seeks to identify subgroups of non-Hodgkin lymphoma (NHL) patients responsive to PD-1 blocking agents. Whether patients with pre-existing rheumatic diseases might constitute such a subgroup is unknown. We determined intratumoral expression of PD-1 and its ligands in lymphoma patients with pre-existing rheumatic diseases. We included 215 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjögren's syndrome with subsequent lymphoma and 74 diffuse large B-cell lymphoma (DLBCL) controls without rheumatic disease. PD-1 and PD-ligand immunohistochemical markers were applied on tumor tissue microarrays. The number of PD-1+ tumor infiltrating leukocytes (TILs) and proportions of PD-L1+ and PD-L2+ tumor cells and TILs were calculated and correlated with clinical data. Expression of PD-L1 in tumor cells and TILs was highest in classical Hodgkin lymphoma and DLBCL. In DLBCLs, expression of PD-1 in TILs and PD-L1 in tumor cells was similar in RA, SLE and controls. In RA-DLBCL, high expression of PD-L1 in tumor cells was significantly more common in patients with the most severe RA disease and was associated with inferior overall survival in multivariable analysis.

Numerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or primary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning-based and network-based analysis identified overexpressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Research shows that alcohol and drug use among mental health clients is common and has the potential to negatively impact treatment outcomes. Internet-delivered cognitive behavior therapy (ICBT) as a treatment for anxiety and depression is on the rise, but little is known about the prevalence of alcohol and drug use among clients and how this use affects treatment completion and outcomes., Objective: The objective of the current study was to explore the prevalence of alcohol and drug use among clients in ICBT for depression and anxiety, and to investigate the impact of alcohol and drug use on treatment completion and symptom outcomes., Material and Methods: Data was collected from 1155 clients who participated in two randomized ICBT trials for depression and anxiety, conducted in a routine care clinic. Thirty-five individuals reporting severe substance use when applying to the trials were excluded. Demographic variables, and alcohol and drug use were measured at screening, and measures of depression and anxiety were administered at pre- and post-treatment., Results: Four out of five clients reported having used alcohol in the past year, while one in five reported having used drugs in the past year. Around a third of clients had reported either problematic alcohol use, drug problems, or both. The analyses showed that drug problems, and combined alcohol and drug problems were negatively associated with treatment completion, but neither alcohol nor drug use had an impact on depression and anxiety outcomes., Conclusions: Alcohol and drug problems are likely to be present among a large proportion of patients using ICBT for anxiety and depression. This may not be a barrier to treatment benefit, at least when those with severe alcohol and drug problems have been excluded., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that appear to have influenced the work reported in this paper., (© 2021 The Authors.)

Background: There is a growing interest in offering therapist-guided internet interventions for alcohol use disorders (AUD) in regular addiction services. Elucidating the therapeutic processes during these interventions may help improve clinical delivery. The aim of this paper was to investigate written messages from client to therapist in a therapist-guided internet intervention for AUD., Methods: Data was extracted from the therapist-guided arm ( n  = 57) of a randomized trial of internet interventions for AUD. Qualitative content analysis was used to identify distinct categories of client behaviors in written messages to therapists. Coding was deductive (applying categories from past literature) as well as inductive (identifying new categories from the data). Subsequently, exploratory correlational and regression analyses were conducted to investigate whether identified client behaviors predicted module completion and drinking outcomes. Also, client questions posed in messages to therapists were categorized separately., Results: Eleven distinct behavior categories were identified, of which the two most common were alliance (26.6% of total categorizations) and identifying patterns and problem behaviors (22.8%). Confrontational alliance rupture was the least common category (0.4%). One new behavior category was identified inductively - alcohol-related setback (4.1%). In the exploratory analyses, no categories consistently predicted module completion or drinking outcomes. Client questions were most commonly posed to improve understanding or use of program content or skills., Discussion: The behavior categories, although not predictive of module completion or outcomes, may be of use for therapists, treatment developers and health care providers as a tool for understanding therapeutic processes in internet interventions for AUD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)