BACKGROUND: The present study investigated the predictive relationship between ostracism and suicidal behaviors in individuals with substance use disorders. It also attempts to highlight the mediating role of the risk of relapse between ostracism and suicidal behavior.
METHODS: The study was based on a cross-sectional survey design. The sample comprised 100 men aged between 30 to 45 years (M = 35.25, SD = 3.06) from Karachi. The purposive sampling technique was employed. The study employed demographic forms and three self-reporting measures: the Ostracism Experience Scale (OES-A), the Advance Warning of Relapse Questionnaire 3.0 (AWARE), and the Suicide Behaviors Questionnaire-Revised (SBQ-R).
RESULTS: Ostracism significantly predicted relapse risk and suicidal behavior. Risk of relapse positively predicted both dimensions of ostracism (ignored: r = 0.33, p < 0.01; excluded: r = 0.43, p < 0.01) and suicidal behavior (r = 0.35, p < 0.01). Additionally, the risk of relapse strongly correlated with overall ostracism score (r = 0.43, p < 0.01). However, no significant mediating effect of ostracism on suicidal behavior was found. The effect was mediated through the risk of relapse (B indirect = 0.12, 95% CI = 0.04, 0.23). These findings suggest that ostracism increases the likelihood of recurrence, which in turn is associated with suicidal behavior. The mediation model explained 17% of the variation in suicidal behavior.
CONCLUSIONS: The findings propose the importance of addressing ostracism as a risk factor for suicidal behavior and relapse in substance use disorders. The results suggest that reducing the adverse effects of ostracism and improving social support for individuals can have a significant impact on their mental health.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

UNASSIGNED: Anthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide therapeutic benefit with less cardiotoxicity. Acute changes in left ventricular systolic function and cardiac biomarkers were evaluated after a cycle of CPX-351 in children with relapsed AML treated on the phase 1/2 Children\'s Oncology Group study, AAML1421.
UNASSIGNED: Subjects received 135 units/m2/dose of CPX-351 on days 1, 3, and 5 as cycle 1. Echocardiograms were performed and centrally quantitated at baseline and at the end of cycle 1 (day 29 +/- 1 week). High sensitivity troponin (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and serially through the end of cycle 1 (days 5, 8, 15, 22 and 29). Differences between baseline and post-CPX-351 echo/biomarker measures were analyzed using Wilcoxon signed rank tests. Linear regression was used to model post-CPX-351 left ventricular ejection fraction (LVEF) with cTnT/NT-proBNP at each time point, controlling for baseline LVEF. Cancer therapy related cardiac dysfunction (CTRCD) was defined as a decline in LVEF of ≥10%-<50%.
UNASSIGNED: Twenty-five of 38 heavily anthracycline pre-treated (median 348 mg/m2 daunorubicin equivalents) subjects enrolled on AAML1421 were included in the cardiac analyses. At baseline, centrally quantitated LVEF was <50% in 8 of 25 subjects (32%) with a median LVEF of 53.8% [48.0, 56.9]. Following CPX-351, LVEF declined significantly (ΔLVEF -3.3% [-7.8, 0]) and 6 of 25 subjects (24%) experienced CTRCD. Amongst all subjects, hs-cTnT was modestly increased at end of cycle 1 compared to baseline [baseline hs-cTnT 7.2 (3, 10.6); ΔcTnT 1.80 (0, 6.1), p = 0.03]. NT-proBNP remained stably elevated without significant change. No significant associations were seen between NT-proBNP or cTnT levels and post-CPX-351 LVEF.
UNASSIGNED: In this single arm study of anthracycline pre-treated children exposed to CPX-351, baseline abnormalities in cardiovascular function were prevalent. Following CPX-351, LVEF decreased, cTnT increased, and NT-proBNP did not change. Longer follow-up is needed to determine whether these changes result in clinically meaningful long-term decrements in cardiac function. An ongoing randomized trial of CPX-351 compared to standard anthracyclines in anthracycline naïve patients will provide further insight into the cardiac effects of CPX-351 (ClinicalTrials.gov; NCT04293562).

UNASSIGNED: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
UNASSIGNED: We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
UNASSIGNED: We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
UNASSIGNED: In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space.

UNASSIGNED: The somatic mutation of fms-like tyrosine kinase 3 (FLT3) in acute myeloid leukemia (AML) is associated with increased risk of relapse and lower survival rates. FLT3i as maintenance after allogeneic hematopoietic stem cell transplant (allo-HSCT) are under study to prevent disease relapse, but real-world data are lacking.
UNASSIGNED: We performed a single center, retrospective cohort study and analyzed patients who had FLT3-mutated AML and underwent allogeneic-HSCT between January 2011 to June 2022 at the University of Chicago. We identified 23 patients who received FLT3i maintenance therapy post-allo-HSCT and compared their outcomes against 57 patients who did not. Primary outcome was disease-free survival (DFS). Secondary outcomes include overall survival (OS) and relapse rate.
UNASSIGNED: FLT3i maintenance therapy was started at a median 59 days (range, 29-216 days) after allo-HSCT with median duration of 287 days (range, 15-1,194 days). Maintenance therapy was well tolerated. Overall, the improvement in DFS rates for patients after they were placed on FLT3i maintenance therapy was not significant [hazard ratio (HR) for relapse or death =0.65, 95% confidence interval (CI): 0.32-1.31, P=0.23]. However, when adjusted for the conditioning regimen and donor status, the differences were statistically significant with improvement in DFS and OS for patients on FLT3i maintenance (HR for OS =0.42, 95% CI: 0.18-0.95, P=0.04).
UNASSIGNED: When adjusting for conditioning regimen and donor status, there was a significant improvement in DFS and OS for patients who received FLT3i maintenance therapy compared to those who did not. Randomized prospective studies may provide more insight.

Aim: This exploratory study analyses the interplay between the treatment philosophies of Alcoholics Anonymous (AA) and Relapse Prevention (RP) in personal stories of addiction. While the basic ideas of AA and RP are compatible in many ways, they also carry some fundamental differences. Methods: The data consisted of interviews with 12 individuals recovering from substance use problems, who had experience of both AA and RP. The analysis drew on a dialogical narrative perspective, and the concept polyphony was used to shed light on the interplay between different treatment philosophies in personal stories of relapse. Findings: Although sometimes resulting in incoherence, the treatment philosophies were combined idiosyncratically, in ways that appeared productive for the participants\' self-images and recovery journeys. Conclusion: The combination of AA and RP philosophies in narratives of relapse and recovery may reflect a new treatment discourse where individualisation and responsibilisation stand in a complicated relationship with collectivism and surrendering to so-called addicting processes.

Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting.
METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5.
RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities.
CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related classification issues, as well as genetic features of relapsed pediatric ETP-ALL. Between 2017 and 2022, 7518 patients were diagnosed with acute leukemia (AL). In addition to conventional immunophenotyping, karyotyping, and FISH studies, we performed next-generation sequencing of the T-cell receptor clonal repertoire and reverse transcription PCR and RNA sequencing for patients with ETP-ALL at both initial diagnosis and relapse. Among a total of 534 patients diagnosed with T-cell ALL (7.1%), 60 had ETP-ALL (11.2%). Ten patients with ETP-ALL experienced relapse or progression on therapy (16.7%), with a median time to event of 5 months (ranging from two weeks to 5 years). Most relapses were classified as AL of ambiguous lineage (n = 5) and acute myeloid leukemia (AML) (n = 4). Major genetic markers of leukemic cells remained unchanged at relapse. Of the patients with relapse, four had polyclonal leukemic populations and a relapse with AML or bilineal mixed-phenotype AL (MPAL). Three patients had clonal TRD rearrangements and relapse with AML, undifferentiated AL, or retention of the ETP-ALL phenotype. ETP-ALL relapse requires careful clinical and laboratory diagnosis. Treatment decisions should rely mainly on initial examination data, taking into account both immunophenotypic and molecular/genetic characteristics.