Gestational trophoblastic neoplasm: Patient outcomes and clinical pearls from a multidisciplinary referral center.

Objectives: To describe clinical outcomes and pearls for patients with gestational trophoblastic neoplasm (GTN).

Methods: Patients with GTN treated at a referral center from 1/2006 to 12/2022 were included. Clinical characteristics, World Health Organization risk score (low-risk 0-6, high-risk ≥7), and treatments/outcomes were evaluated using summary statistics, stratified by initial treatment at a referral center versus locally.

Safe Integration of Encorafenib plus Binimetinib with Stereotactic Radiosurgery for Melanoma Brain Metastases: a Case Report.

Background: Melanoma brain metastases represents a significant clinical challenge, frequently associated with high morbidity and mortality. Recent advancements in neuroimaging, radiation therapy, and targeted systemic therapies, specifically BRAF and MEK inhibitors, have improved the management of this condition. Nevertheless, the optimal therapeutic approach for melanoma brain metastases remains a subject of ongoing debate, with no universally accepted treatment protocol.

Genetically modified and unmodified cellular approaches to enhance graft versus leukemia effect, without increasing graft versus host disease: the use of allogeneic cytokine-induced killer cells.

Although allogeneic hematopoietic cell transplantation (HCT) represents a curative approach for many patients with hematological diseases, post-transplantation relapse occurs in 20-50% of cases, representing the primary cause of treatment failure and mortality. Alloreactive donor T cells are responsible for the graft versus leukemia (GvL) effect, which represents the key mechanism for the long-term curative effect of HCT. However, the downside is represented by graft versus host disease (GvHD), largely contributing to transplant-related mortality (TRM).

Long-term real world evidence of CPX-351 of high-risk AML patients identified high rate of negative MRD and prolonged OS.

CPX-351 has been approved for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). No extensive data are available on MRD and long-term clinical outcome using CPX-351 in AML in real-life. We retrospectively collected data from 168 patients in 36 centers in France and Italy who had received one or two cycles of induction with CPX-351.

B Cell Responses to the Placenta and Fetus.

Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust, and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies from harming the placenta and fetus.

Are lateralized and bold fish optimistic or pessimistic?

Cognitive bias is defined as the influence of emotions on cognitive processes. The concept of the cognitive judgement bias has its origins in human psychology but has been applied to animals over the past 2 decades. In this study we were interested in determining if laterality and personality traits, which are known to influence learning style, might also be correlated with a cognitive bias in the three-spined sticklebacks (Gasterosteus aculeatus).

Safety and efficacy of narsoplimab in pediatric and adult patients with transplant-associated thrombotic microangiopathy: a real-world experience.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation (HSCT). No approved treatments are currently available. This study presents real-world data obtained with narsoplimab, a human immunoglobulin G4 monoclonal antibody that inhibits MASP-2, the effector enzyme of the lectin pathway of the complement system.

Validation of a murine proteome-wide phage display library for identification of autoantibody specificities.

Autoimmunity is characterized by loss of tolerance to tissue-specific as well as systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics of a murine proteome-wide library for phage display immunoprecipitation and sequencing (PhIP-seq) in profiling mouse autoantibodies. This library was validated using 7 genetically distinct mouse lines across a spectrum of autoreactivity.

Evaluating a low anion gap: A practical approach.

In teaching and in practice, little attention is given to a low anion gap. This oversight can result in a missed opportunity to diagnose acute or chronic disorders requiring treatment. In this article, we review the constituents of the anion gap, build a differential diagnosis for a low anion gap using case examples, and provide a stepwise approach to diagnostic testing to evaluate this abnormal finding.

Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies.

While regulatory T (T) cells are traditionally viewed as professional suppressors of antigen presenting cells and effector T cells in both autoimmunity and cancer, recent findings of distinct T cell functions in tissue maintenance suggest that their regulatory purview extends to a wider range of cells and is broader than previously assumed. To elucidate tumoral T cell 'connectivity' to diverse tumor-supporting accessory cell types, we explored immediate early changes in their single-cell transcriptomes upon punctual T cell depletion in experimental lung cancer and injury-induced inflammation. Before any notable T cell activation and inflammation, fibroblasts, endothelial and myeloid cells exhibited pronounced changes in their gene expression in both cancer and injury settings.

Validation of a murine proteome-wide phage display library for the identification of autoantibody specificities.

Autoimmunity is characterized by loss of tolerance to tissue-specific as well as systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics of a murine proteome-wide library for phage display immunoprecipitation and sequencing (PhIP-seq), to profile mouse autoantibodies. This system and library were validated using seven genetic mouse models across a spectrum of autoreactivity.

T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants.

Cancer immunotherapies, including adoptive T cell transfer, can be ineffective because tumors evolve to display antigen-loss-variant clones. Therapies that activate multiple branches of the immune system may eliminate escape variants. Here, we show that melanoma-specific CD4 T cell therapy in combination with OX40 co-stimulation or CTLA-4 blockade can eradicate melanomas containing antigen escape variants.

A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.

Mature T cells must discriminate between brief interactions with self-peptides and prolonged binding to agonists. The kinetic proofreading model posits that certain T-cell antigen receptor signaling nodes serve as molecular timers to facilitate such discrimination. However, the physiological significance of this regulatory mechanism and the pathological consequences of disrupting it are unknown.

AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia.

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.

Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020.

Trophoblast antigens, fetal blood cell antigens, and the paradox of fetomaternal tolerance.

The paradox of fetomaternal tolerance has puzzled immunologists and reproductive biologists alike for almost 70 yr. Even the idea that the conceptus evokes a uniformly tolerogenic immune response in the mother is contradicted by the long-appreciated ability of pregnant women to mount robust antibody responses to paternal HLA molecules and RBC alloantigens such as Rh(D). Synthesizing these older observations with more recent work in mice, we discuss how the decision between tolerance or immunity to a given fetoplacental antigen appears to be a function of whether the antigen is trophoblast derived-and thus decorated with immunosuppressive glycans-or fetal blood cell derived.

Severe Activity of Inflammatory Bowel Disease is a Risk Factor for Severe COVID-19.

Background: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids.

Methods: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes.

Establishment of fetomaternal tolerance through glycan-mediated B cell suppression.

Discrimination of self from non-self is fundamental to a wide range of immunological processes. During pregnancy, the mother does not recognize the placenta as immunologically foreign because antigens expressed by trophoblasts, the placental cells that interface with the maternal immune system, do not activate maternal T cells. Currently, these activation defects are thought to reflect suppression by regulatory T cells.

Effectiveness and safety of an on-demand ferric carboxymaltose infusion strategy in patients with inflammatory bowel disease: a real world experience.

Background: We evaluated an on-demand ferric carboxymaltose (FCM) infusion strategy in inflammatory bowel disease (IBD) patients with iron deficiency anemia (IDA).

Aims: The primary outcome was the response rate to single or multiple FCM infusions after 12 months. Secondary outcomes were the response rate to a single FCM infusion after 3 months and the FCM safety profile.

Sequential allogeneic transplantation and ruxolitinib maintenance for a synchronous positive myeloid sarcoma and acute B-lymphoblastic leukemia.

The translocation t(8;9)(p22;p24) results in the production of a chimeric - fusion protein leading to the constitutive activation of the Janus Kinase 2 that renders this disease potentially sensitive to ruxolitinib. Here, we report an interesting case of - myeloproliferative neoplasm evolving in myeloid sarcoma and B precursor ALL.

Cyclophosphamide enhances the antitumor potency of GITR engagement by increasing oligoclonal cytotoxic T cell fitness.

Only a subset of cancer patients responds to checkpoint blockade inhibition in the clinic. Strategies to overcome resistance are promising areas of investigation. Targeting glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) has shown efficacy in preclinical models, but GITR engagement is ineffective in controlling advanced, poorly immunogenic tumors, such as B16 melanoma, and has not yielded benefit in clinical trials.