Utility of loop diuretics as a marker of risk in clinical trials of heart failure with preserved ejection fraction: Analysis from the Swedish Heart Failure Registry.

Aims: It is common in heart failure (HF) trials, especially in HF with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF), to select for increased risk of outcomes ('enrichment'). We investigated the association between loop diuretic use and common trial outcomes.

Methods And Results: Patients in the Swedish HF Registry with HFmrEF and HFpEF were divided into three groups: no loop diuretic use, 1-40 mg furosemide equivalent, and >40 mg.

Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: Data from Swedish Heart Failure Registry.

Aims: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.

Methods And Results: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry.

HTGQC and shinyHTGQC: an R package and shinyR application for quality controls of HTG EDGE-seq protocols.

Unlabelled: Extraction-free HTG EdgeSeq protocols are used to profile sets of genes and measure their expression. Thus, these protocols are frequently used to characterise tumours and their microenvironments. However, although positive and control genes are provided, little indication is given concerning the assessment of the technical success of each sample within the sequencing run.

Targeting IRAK4 with Emavusertib in Lymphoma Models with Secondary Resistance to PI3K and BTK Inhibitors.

Inhibitors of phosphatidylinositol 3-kinase (PI3K) and Bruton tyrosine kinase (BTK) represent a recognized option for the treatment of patients affected by indolent B cell lymphomas. However, small molecules as single agents show limited success in their ability in inducing complete responses, with only partial remission achieved in most patients, suggesting the need for combination therapies. IRAK4 is a protein kinase downstream of the Toll-like receptor signaling (TLR), a driver pathway of secondary tumor° resistance in both hematological and solid tumor malignancies.

Enhancer RNAs (eRNAs) in Cancer: The Jacks of All Trades.

Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn.

Characterization of GECPAR, a noncoding RNA that regulates the transcriptional program of diffuse large B-cell lymphoma.

Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNA (eRNA) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNA stabilize contacts between distal genomic regions and mediate the interaction of DNA with master transcription factors.

Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma models.

Antibody drug conjugates represent an important class of anti-cancer drugs in both solid tumors and hematological cancers. Here, we report preclinical data on the anti-tumor activity of the first-in-class antibody drug conjugate MEN1309/OBT076 targeting CD205. The study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination and validation experiments on in vivo models.

Right Ventricular Failure: Pathophysiology, Diagnosis and Treatment.

The prognostic significance of the right ventricle (RV) has recently been recognised in several conditions, primarily those involving the left ventricle, the lungs and their vascular bed, or the right-sided chambers. Recent advances in imaging techniques have created new opportunities to study RV anatomy, physiology and pathophysiology, and contemporary research efforts have opened the doors to new treatment possibilities. Nevertheless, the treatment of RV failure remains challenging.

Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma.

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy.

PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy.

Activation of the PI3K/mTOR signaling pathway is recurrent in different lymphoma types, and pharmacologic inhibition of the PI3K/mTOR pathway has shown activity in lymphoma patients. Here, we extensively characterized the and activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical lymphoma models. This study included preclinical activity screening on a large panel of cell lines, both as single agent and in combination, validation experiments on models and primary cells, proteomics and gene-expression profiling, and comparison with other signaling inhibitors.

Evaluation of volumetric dimensional changes in posterior extraction sites with and without ARP using a novel imaging device.

Background: Alveolar ridge volume loss may be minimized when postextraction sockets are filled by bone substitutes.

Purpose: The aim of the study was to measure the effect of alveolar ridge preservation (ARP) in maintaining the external contour of the ridge after fresh socket grafting with or without particulate anorganic bovine bone mineral (BBM) and resorbable barrier covering.

Materials And Methods: In the present controlled study, patients subjected to single-tooth extraction were allocated to 2 groups: postextraction sockets grafted with bovine bone mineral (bbm), and naturally healing sockets (nat).