Recipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.

Benralizumab: from tissue distribution to eosinophilic cytotoxicity up to potential immunoregulation.

Introduction: Benralizumab, a monoclonal IgG antibody, has emerged as a key therapeutic agent in severe asthma by specifically targeting eosinophils, pivotal cells that drive inflammation and tissue damage. Over the past two decades, the availability of such targeted therapies has allowed patients to achieve better disease control. Real-world evidence has consistently demonstrated the effectiveness of benralizumab in managing severe asthma.

Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency.

Tissue-resident memory T (T) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T cell fate remains poorly understood. Here, we show that whereas skin T cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T cells in the small intestine.

Real-world evidence on tagraxofusp for blastic plasmacytoid dendritic cell neoplasm - collected cases from a single center and case reports.

Introduction: Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare, aggressive hematologic malignancy. Until recently, the only curative treatment consisted of intensive chemotherapy, followed by hematopoietic cell transplantation (HCT) in eligible adult cases. Tagraxofusp, a CD123-targeted protein-drug conjugate and the first approved targeted treatment for BPDCN, might enhance outcomes especially in patients not eligible for intensive therapies.

Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics.

Patients And Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks.

Exploring the risk of infection events in patients with asthma receiving -IL-5 monoclonal antibodies: A rapid systematic review and a meta-analysis.

Introduction: Benralizumab, mepolizumab, and reslizumab are novel monoclonal antibodies approved for asthma, targeting eosinophilic inflammation. Benralizumab is directed against IL-5 receptor (IL-5R), while mepolizumab and reslizumab are directed against IL-5. The three drugs cause a reduction in eosinophils, but benralizumab also causes a cytotoxic effect on eosinophils and basophils.

Active Moms: a feasibility study of a community-based and home-based physical activity intervention for low-income, ethnic-minority mothers.

Background: Despite the health benefits of physical activity, increasing regular physical activity levels among low-income, ethnic-minority mothers has remained a significant challenge. Yet, few studies have examined the feasibility of implementing interventions to address physical activity barriers often experienced by this population.

Methods: The current mixed-methods pilot study assessed the feasibility, impact, and acceptability of a 3-month community-based (CBI) and a home-based intervention (HBI) designed to improve physical activity and fitness levels, as well as psychosocial outcomes (self-efficacy and social support), among low-income, ethnic minority mothers.

Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.

Unraveling the complexities of drug reaction with eosinophilia and systemic symptoms (DRESS): Insights into clinical, laboratory, and histopathologic features of a case series from an Italian tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life-threatening drug hypersensitivity reaction. The diagnosis and management of DRESS are complicated due to its heterogeneous clinical and pathologic presentations, delayed onset of signs and symptoms, and unpredictable outcome. This retrospective study aimed to analyze cases of DRESS from a single Italian referring tertiary hospital center (Grande Ospedale Metropolitano Niguarda, Milan, Italy) with a focus on clinical features, causative drugs, histopathologic findings, and treatment.

Safety and adverse reactions in subcutaneous allergen immunotherapy: a review.

Background: Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection.

Single-cell protein expression profiling resolves circulating and resident memory T cell diversity across tissues and infection contexts.

Memory CD8 T cells can be broadly divided into circulating (T) and tissue-resident memory T (T) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of T and T cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in T and T cells in solid organs and barrier locations.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

Background: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks.

Methods: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization).

CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity.

Antiviral CD8 T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4 T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone.

The clinical and pathologic spectrum of mucocutaneous reactions after COVID-19 vaccinations in three tertiary referral centers of northern Italy.

Adverse cutaneous reactions after COVID-19 vaccinations have increased, highlighting not only how SARS-CoV-2 infection but also COVID-19 vaccines may induce adverse cutaneous manifestations. We evaluated the clinical and pathologic spectrum of mucocutaneous reactions after COVID-19 vaccinations, observed consecutively within three large tertiary centers of the Metropolitan City of Milan (Lombardy), comparing our results with the currently available literature. We retrospectively reviewed medical records and skin biopsies of patients diagnosed with mucocutaneous adverse events after COVID-19 vaccinations and followed at three Italian tertiary referral centers in the Metropolitan City of Milan.

Acute effects of an exercise based multimodal in-patient rehabilitation protocol in male knee osteoarthritis patients and the two years follow-up sustainability.

Background: Working with lifting and carrying heavy loads and kneeling postures with crawling, squats or heel seat position lead to progressive cartilage wear with premature degenerative changes.

Objective: To investigate the effects of the exercise based multimodal 'knee college' and its sustainability in patients with knee osteoarthritis with data assessments before and after a starter course, before a 1-year and a 2-year follow-up refresher course in a retrospective observational study.

Methods: A sample of 401 male patients (ICD10: M17 [arthrosis of knee]/ICF: s75011 [knee joint]) from the construction industries were assessed with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol (EQ-5D), Performance Assessment Capacity Testing (PACT), Isokinetic torque H/Q ratio and Physical Work Capacity Test (PWC).

Nr6a1 controls Hox expression dynamics and is a master regulator of vertebrate trunk development.

The vertebrate main-body axis is laid down during embryonic stages in an anterior-to-posterior (head-to-tail) direction, driven and supplied by posteriorly located progenitors. Whilst posterior expansion and segmentation appears broadly uniform along the axis, there is developmental and evolutionary support for at least two discrete modules controlling processes within different axial regions: a trunk and a tail module. Here, we identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of trunk development in the mouse.

Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm: A Post Hoc Analysis from the ANANKE Study.

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300-450 cells/mm subset of patients.

Airborne anaphylaxis: highlighting an invisible enemy.

Purpose Of Review: Airborne anaphylaxis is a rare disorder defined by the occurrence of anaphylactic reactions to inhaled allergens, which may arise not only in occupational exposure but also in common settings. Foods are the most common cause of airborne anaphylaxis, even organic mixtures scents. The other important cause is represented by drugs, while in the wide range of other causes, there are often reports on unique cases.