Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate approved for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low-intensity chemotherapy or other anti-ALL-targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher-risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T-cell therapy, to eliminate measurable residual disease and to prevent post-HSCT relapse.

KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression.

Intention-to-treat outcomes utilising a stringent event definition in children and young people treated with tisagenlecleucel for r/r ALL through a national access scheme.

CAR T-cell therapy has transformed relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukaemia (B-ALL) management and outcomes, but following CAR T infusion, interventions are often needed. In a UK multicentre study, we retrospectively evaluated tisagenlecleucel outcomes in all eligible patients, analysing overall survival (OS) and event-free survival (EFS) with standard and stringent definitions, the latter including measurable residual disease (MRD) emergence and further anti-leukaemic therapy. Both intention-to-treat and infused cohorts were considered.

Paediatric syndromic scoliosis: proceedings of the half-day course at the 57th annual meeting of the Scoliosis Research Society.

There are some syndromes that present with unique manifestations pertaining to the spinal column. A good working understanding of these common syndromes is useful for the spinal deformity surgeons and related healthcare providers. This review attempts to encompass these unique features and discuss them in three broad groups: hypermobility syndromes, muscle pathology-related syndromes, and syndromes related to poor bone quality.

Management of ALL in adults: 2024 ELN recommendations from a European expert panel.

Experts from the European Leukemia Net (ELN) working group for adult acute lymphoblastic leukemia have identified an unmet need for guidance regarding management of adult acute lymphoblastic leukemia (ALL) from diagnosis to aftercare. The group has previously summarized their recommendations regarding diagnostic approaches, prognostic factors, and assessment of ALL. The current recommendation summarizes clinical management.

Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel.

Working groups of the European LeukemiaNet have published several important consensus guidelines. Acute lymphoblastic leukemia (ALL) has many different clinical and biological subgroups and the knowledge on disease biology and therapeutic options is increasing exponentially. The European Working Group for Adult ALL has therefore summarized the current state of the art and provided comprehensive consensus recommendations for diagnostic approaches, biologic and clinical characterization, prognostic factors, and risk stratification as well as definitions of endpoints and outcomes.

Homeostasis Theory of Well-being.

The Homeostasis Theory of Well-being proposes a homeostatic modular system for the creation of human well-being. This article aims to: (i) provide a proof-of-concept demonstration of the feasibility of the theory in its biopsychosocial context; (ii) indicate prima facie empirical support for the homeostatic nature of the 16 proposed modules; (iii) discuss the similarities to and differences from other homeostasis theories of well-being. Following the Central Limit Theorem, any homeostatic system with multiple inputs produces outputs with a Gaussian distribution.

Does intervertebral disc degeneration in adolescent idiopathic scoliosis correlate with patient-reported pain scores? A review of 968 cases.

Purpose: Report the rate and severity of degenerative disc disease (DDD) in non-surgical adolescent idiopathic scoliosis (AIS) patients and correlate these findings with patient-reported symptomatology scores. Additionally, to quantify the rate of concurrent pathological radiological findings in this group.

Methods: This was a retrospective chart review study at a single tertiary centre.

Defining and 'diagnosing' aphantasia: Condition or individual difference?

Research into the newly-coined 'condition' of 'aphantasia', an individual difference involving the self-reported absence of voluntary visual imagery, has taken off in recent years, and more and more people are 'self-diagnosing' as aphantasic. Yet, there is no consensus on whether aphantasia should really be described as a 'condition', and there is no battery of psychometric instruments to detect or 'diagnose' aphantasia. Instead, researchers currently rely on the Vividness of Visual Imagery Questionnaire (VVIQ) to 'diagnose' aphantasia.

Phenomenological Studies of Visual Mental Imagery: A Review and Synthesis of Historical Datasets.

This article reviews historically significant phenomenological studies of visual mental imagery (VMI), starting with Fechner in 1860 and continuing to the present. This synthesis of diverse VMI phenomenological studies in healthy adults serves as a unique resource for investigators of individual differences, cognitive development and clinical and neurological conditions. The review focuses on two kinds of VMI, "memory imagery" and "eidetic imagery".

ALL-RIC trial protocol: a comparison of reduced dose total body irradiation (TBI) and cyclophosphamide with fludarabine and melphalan reduced intensity conditioning in adults with acute lymphoblastic leukaemia (ALL) in complete remission.

Introduction: The usage of a T-cell depleted, reduced intensity conditioning (RIC) approach to haematopoietic cell transplantation (HCT) in adult patients with acute lymphoblastic leukaemia (ALL) over 40 years of age and in first complete remission (CR) has resulted in encouraging rates of event-free and overall survival in a population of adults with high risk disease. However, relapse rates remain high-with disease progression being the major cause of treatment failure. Using different, more powerful conditioning approaches is the logical next step in examining the role of RIC allogeneic HCT in adult ALL.

The Action Cycle Theory of Perception and Mental Imagery.

The Action Cycle Theory (ACT) is an enactive theory of the perception and a mental imagery system that is comprised of six modules: Schemata, Objects, Actions, Affect, Goals and Others' Behavior. The evidence supporting these six connected modules is reviewed in light of research on mental imagery vividness. The six modules and their interconnections receive empirical support from a wide range of studies.

Systematic Review and Meta-analysis: Does Anterior-Posterior Spinal Fusion Still have a Role in Severe Thoracic Adolescent Idiopathic Scoliosis?

Background: Debate exists as to whether anterior-posterior spinal fusion (APSF), rather than posterior-only spinal fusion (PSF), provides benefit for treating severe thoracic adolescent idiopathic scoliosis (AIS). This systematic review and meta-analysis compare (1) Cobb angle correction, (2) complication and reoperation rate, (3) pulmonary function, (4) number of fused segments, and 5) patient-reported outcome measures (PROMs) in both groups.

Methods: Electronic databases were searched to identify studies that met the following inclusion criteria: comparative studies (level 3 or above), severe thoracic curves (≥ 70°), age ≤ 16, AIS aetiology, Lenke 1-4 curves and follow-up ≥ 1 year for ≥ 95% of patient population.

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis.

The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC). Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology. Symptom scores of the PASC group and the ME/CFS group correlated 0.

Patient-specific 3D printing to replace components of a rib-to pelvis "Eiffel Tower" vertebral expanding prosthetic titanium rib system in an infant: a case report.

Purpose: To address the anatomical challenges facing complex and revision spinal surgery, patient-specific 3D-printed models (3D-PMs) have received growing attention worldwide, primarily in adults. We report the use of a 3D-PM in the treatment of a case of wound breakdown over a component of a VEPTR (Vertical Expandable Prosthetic Titanium Rib; DePuy-Synthes) system, requiring replacement of Dunn-McCarthy hook and sleeve with components contoured to a patient-specific 3D-PM of the spine.

Method: A two-year-old born with myelomeningocele (MMC), repaired at birth, developed progressive MMC-associated kyphoscoliosis.

Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study.

Background: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required.

Objectives: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery.