Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.

Cyclic AMP (cAMP) has a crucial role in many vital cellular processes and there has been much effort expended in the discovery of inhibitors against the enzyme superfamily that degrades this second messenger, namely phosphodiesterases (PDEs). The journey of competitive PDE inhibitors to the clinic has been hampered by side effects profiles that have resulted from a lack of selectivity for subfamilies and individual isoforms because of high conservation of catalytic site sequences and structures. Here we introduce a proteolysis targeting chimera (PROTAC) that can specifically target a small subset of isoforms from the PDE4 family to send the enzyme for degradation at the proteasome by recruiting a ubiquitin E3 ligase into proximity with the PDE.

Allogeneic hematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for multiple myeloma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Therapy-related myeloid neoplasms (t-MN) are a complication of multiple myeloma (MM) treatment. Our retrospective, EBMT registry study included 157 such patients allografted (allo-HCT) between 2006 and 2018. Most patients (130) had a prior autologous HCT.

Young (<35 years) haploidentical versus old (≥35 years) mismatched unrelated donors and vice versa for allogeneic stem cell transplantation with post-transplant cyclophosphamide in patients with acute myeloid leukemia in first remission: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison).

Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study.

Background: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use.

Method: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3.

Allogeneic haematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for lymphoma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006-2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively.

Improvised dual lumen nasojejunal feeding tube with gastric decompression.

Video 1Improvisation of the nasojejunal tube for gastric outlet obstruction.

Neurodevelopment and early pharmacological interventions in Fragile X Syndrome.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the leading monogenic cause of autism and intellectual disability. For years, several efforts have been made to develop an effective therapeutic approach to phenotypically rescue patients from the disorder, with some even advancing to late phases of clinical trials. Unfortunately, none of these attempts have completely succeeded, bringing urgency to further expand and refocus research on FXS therapeutics.

Cognitive biases in first-episode psychosis with and without attention-deficit/hyperactivity disorder.

Introduction: Psychotic disorders such schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with social cognitive deficits. Specifically, biased interpretation of social information can result in interpersonal difficulties. Cognitive biases are prevalent in psychosis, but no previous study has investigated whether the type and severity of cognitive biases differ between subjects experiencing first-episode psychosis (FEP) with (FEP-ADHD) and without ADHD (FEP-ADHD).

External ventriculostomy-associated infection reduction after updating a care bundle.

Background: Despite the clinical benefits of external ventricular drains (EVD), these devices can lead to EVD-related infections (EVDRI). The drainage insertion technique and standardized guidelines can significantly reduce the risk of infection, mainly caused by gram-positive bacteria. However, gram-negative microorganisms are the most frequent causative microorganisms of EVDRI in our hospital.

Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT.

We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.

Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party.

We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.

Role of allogeneic hematopoietic cell transplant for relapsed/refractory aggressive B-cell lymphomas in the CART era.

Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients.

Non-perinatal listeriosis: Changes in frequency, clinical spectrum and prognostic factors.

Introduction: Listeria monocytogenes infection is a severe disease affecting mainly aged people and patients with immune depression. The incidence of listeriosis seems to be increasing. In the present study cases of listeriosis from two hospitals are analyzed with the aims of studying changes in its incidence, clinical forms of presentation and possible factors associated with mortality.

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers.

Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT.

Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.

Genetic and Epigenetic Characterization of a Discordant -Rearranged Infant Monozygotic Twin Pair.

The rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment-genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant -rearranged infant monozygotic twin pair and their parents, and they were compared to three independent /-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated.

Cognitive Biases Questionnaire for Psychosis (CBQp): Spanish Validation and Relationship With Cognitive Insight in Psychotic Patients.

Cognitive biases are key factors in the development and persistence of delusions in psychosis. The Cognitive Biases Questionnaire for Psychosis (CBQp) is a new self-reported questionnaire of 30 relevant situations to evaluate five types of cognitive biases in psychosis. In the context of the validation of the Spanish version of the CBQp, our objectives were to (1) analyze the factorial structure of the questionnaire with a confirmatory factor analysis (CFA), (2) relate cognitive biases with a widely used scale in the field of delusion cognitive therapies for assessing metacognition, specifically, Beck's Cognitive Insight Scale (BCIS) (1), and, finally, (3) associate cognitive biases with delusional experiences, evaluated with the Peters Delusions Inventory (PDI) (2).

Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma - a LWP-EBMT study.

Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months.