Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.

Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

Repeat Procedures After Pulsed Field Ablation for Atrial Fibrillation: MANIFEST-REDO Study.

Background: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centers and involved a limited number of operators. The electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF are incompletely understood.

Incidence and predictors of weaning failure from veno-arterial extracorporeal membrane oxygenation therapy in patients with cardiogenic shock.

Aims: This study aimed to investigate incidence and predictors of weaning failure and in-hospital death after successful weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock (CS).

Methods And Results: Overall, 685 patients with CS treated with VA-ECMO from 23 tertiary care centres in 7 countries were analysed (median age 57 [interquartile range 49-66] years, 542 [79.1%] male, median lactate 7.

NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.

Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.

Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( = 162) versus cilta-cel ( = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS).

Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.

The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.

Differential Diagnosis of Age-Related Macular Degeneration.

A diagnosis of age-related macular degeneration (AMD) may have a significant impact on a patient's life. Therefore, it is important to consider differential diagnoses, as these can differ considerably from AMD regarding prognosis, inheritance, monitoring and therapy. Differential diagnoses include other macular diseases with drusen, drusen-like changes, monogenic retinal dystrophies, as well as a wide range of other, often rare macular diseases.

[Stress and other risk factors in central serous chorioretinopathy-A myth?].

Since the initial description of central serous chorioretinopathy (CSC) by von Graefe in 1866, various risk factors for this condition have been described and discussed. In addition to established factors, such as the use of corticosteroids, psychosomatic factors, particularly stress, have increasingly come into focus in the literature. Studies have shown that psychological stress and emotional stressors not only impair well-being but also trigger physiological responses that could increase the risk of CSC.

Biomarker-Directed Radiotherapy in Breast Cancer: A Narrative Review.

Importance: Integration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates.

Investigating amygdala nuclei volumes in military personnel with post-traumatic stress disorder, major depressive disorder, and adjustment disorder: A retrospective cross-sectional study using clinical routine data.

Background: Post-traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and Adjustment Disorder (AdjD) are highly prevalent among military personnel, often presenting diagnostic challenges due to overlapping symptoms and reliance on self-reporting. The amygdala, particularly the basolateral complex involved in fear-related memory formation and extinction recall, plays a crucial role in emotional processing. Abnormalities in these amygdala nuclei are implicated in PTSD and may distinguish it from other disorders like MDD and AdjD, where these mechanisms are less central.

Promotion of Cardiovascular Health in Africa: The Alliance for Medical Research in Africa (AMedRA) Expert Panel.

This proposed scientific statement is focused on providing new insights regarding challenges and opportunities for cardiovascular health (CVH) promotion in Africa. The statement includes an overview of the current state of CVH in Africa, with a particular interest in the cardiometabolic risk factors and their evaluation through metrics. The statement also explains the main principles of primordial prevention, its relevance in reducing noncommunicable disease and the different strategies that have been effective worldwide.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

Relationships of eating behaviors with psychopathology, brain maturation and genetic risk for obesity in an adolescent cohort study.

Unhealthy eating, a risk factor for eating disorders (EDs) and obesity, often coexists with emotional and behavioral problems; however, the underlying neurobiological mechanisms are poorly understood. Analyzing data from the longitudinal IMAGEN adolescent cohort, we investigated associations between eating behaviors, genetic predispositions for high body mass index (BMI) using polygenic scores (PGSs), and trajectories (ages 14-23 years) of ED-related psychopathology and brain maturation. Clustering analyses at age 23 years ( = 996) identified 3 eating groups: restrictive, emotional/uncontrolled and healthy eaters.

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis.

Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval.

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months.

Minimally invasive versus open surgery for nonfunctioning pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

Introduction: Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) have been diagnosed increasingly often but still represent rare pancreatic neoplasms. Surgery is a potentially curative approach for patients with NF-PNETs. In recent years, minimally invasive surgery (MIS) has been applied more frequently for surgical resection of NF-PNETs.

Nerve transfer of the median flexor pollicis brevis branch to the deep branch of the ulnar nerve for ulnar nerve palsy: a cadaveric feasibility study.

An ulnar nerve (UN) palsy is devastating for hand function, resulting in an intrinsic minus position or claw hand with a loss of pinch grip. Distal nerve transfers facilitate faster reinnervation of hand intrinsic muscles in cases of proximal ulnar nerve lesions. The traditional anterior interosseous nerve (AIN) to UN motor transfer is commonly used, however, this still leads to long reinnervation times for the distal intrinsic muscles, important for the thumb to index pinch grip.

Lutetium-177 PSMA radioligand therapy in taxan-naive first- and second-line metastatic castration resistant prostate cancer after first-line ARPI therapy.

Purpose: Lutetium-177 Prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is EMA-approved for metastatic castration resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition (ARPI) and taxan-based chemotherapy. However, its effect in taxan-naïve patients is under current investigation.

Methods: We relied on the FRAMCAP database to elaborate Lu-PSMA therapy outcomes of progression-free (PFS) and overall (OS) in taxan-naïve mCRPC patients after previous ARPI treatment.

Efficacy and safety of antiviral therapies for the treatment of persistent COVID-19 in immunocompromised patients since the Omicron surge: a systematic review.

Background: Persistent COVID-19 (pCOVID-19) in immunocompromised patients is characterized by unspecific symptoms and pulmonary infiltrates due to ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication. Treatment options remain unclear, leading to different approaches, including combination therapy and extended durations. The purpose of this study was to assess the efficacy and safety of antiviral therapies for pCOVID-19 in immunocompromised patients since the Omicron surge.