CAR T access and outcomes in large B-cell lymphoma according to ethnicity and socioeconomic deprivation in the UK.

Data on the impact of ethnic and socioeconomic factors on Chimeric antigen receptor (CAR) T-cell therapy (access and outcomes are limited, but key to understand whether results from the registration trials are generalizable to real-world patient populations. Here, we analysed ethnicity, socioeconomic deprivation and referral patterns in a cohort of 314 large B-cell lymphoma patients approved for third-line CD19 CAR-T across three large UK CAR-T centres. Patients from deprived areas had a lower infusion rate compared to low deprivation areas (73% vs.

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL.

KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas.

Loss-of-function mutations in KMT2D are a striking feature of germinal center (GC) lymphomas, resulting in decreased histone 3 lysine 4 (H3K4) methylation and altered gene expression. We hypothesized that inhibition of the KDM5 family, which demethylates H3K4me3/me2, would reestablish H3K4 methylation and restore the expression of genes repressed on loss of KMT2D. KDM5 inhibition increased H3K4me3 levels and caused an antiproliferative response in vitro, which was markedly greater in both endogenous and gene-edited KMT2D mutant diffuse large B-cell lymphoma cell lines, whereas tumor growth was inhibited in KMT2D mutant xenografts in vivo.

Pathogenesis of follicular lymphoma: genetics to the microenvironment to clinical translation.

Follicular lymphoma (FL) represents a heterogeneous disease both clinically and biologically. The pathognomonic t(14;18) translocation can no longer be thought of as the primary genetic driver, with increasing recognition of the biological relevance of recurrent genetic alterations in epigenetic regulators that now feature as a pivotal hallmark of this lymphoma subtype. Furthermore, sequencing studies have provided a near complete catalogue of additional genetic aberrations.

The Biological Basis of Histologic Transformation.

Histologic transformation of follicular lymphoma remains the leading cause of follicular lymphoma-related mortality in the rituximab era. Both the diverse timing of transformation and heterogeneity in associated genomic events suggest that histologic transformation may itself comprise distinct disease entities. Successive indolent and transformation episodes occur by divergent clonal evolution from an inferred common progenitor cell, representing a potential therapeutic target.

Precision medicine and lymphoma.

Purpose Of Review: The treatment of the germinal center lymphomas, diffuse large B cell (DLBCL) and follicular lymphoma, has changed little beyond the introduction of immunochemotherapies. However, there exists a substantial group of patients within both diseases for which improvements in care will involve appropriate tailoring of treatment.

Recent Findings: DLBCL consists of two major subtypes with striking differences in their clinical outcomes paralleling their underlying genetic heterogeneity.

Clinical characteristics and outcomes of HIV-associated immune complex kidney disease.

Background: The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease.

Methods: In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN).

Renal tubular disease in the era of combination antiretroviral therapy.

Objectives: To describe the spectrum of renal tubular disease (RTD) in HIV-positive patients and its association with exposure to antiretroviral therapy (ART).

Design: Review of 265 consecutive renal biopsies from HIV-positive patients attending eight clinics in the United Kingdom between 2000 and 2012.

Methods: We described the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART [tenofovir (TDF), atazanavir (ATV), indinavir (IDV) and lopinavir/ritonavir (LPV/r)].

Use of real-time ultrasound guidance for the placement of hemodialysis catheters: a systematic review and meta-analysis of randomized controlled trials.

Background: Insertion of percutaneous hemodialysis catheters is an invasive procedure with a small but definite risk of morbidity and mortality.

Objectives: Assessing potential benefits of using real-time 2-dimensional Doppler ultrasound imaging guidance for the insertion of hemodialysis catheters compared with insertion based solely on anatomic landmarks.

Study Design: Systematic review and meta-analysis of randomized controlled trials.

Ultrasound use for the placement of haemodialysis catheters.

Background: A significant proportion of patients starting dialysis do so with a temporary or tunnelled haemodialysis catheter. Insertion of these catheters can be achieved either by using the anatomical landmarks for the veins into which they are inserted or using ultrasound guidance. It has been suggested that the use of ultrasound guidance reduces the immediate complications of haemodialysis catheter insertions such as pneumothorax or arterial puncture.