Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation.

Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS.

Clinical implications of frailty assessed in hospitalized patients with acute-exacerbation of interstitial lung disease.

Background: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery.

BRAT1-Associated Leukodystrophy Exacerbated by Classic Hodgkin Lymphoma-Directed Therapy.

Introduction: BRCA1-associated ataxia-telangiectasia-mutated activator-1 (BRAT1) is responsible for cell cycle surveillance and mitochondrial function. The implications of adult-onset BRAT1-variant and the resulting phenotypic neurocognitive and imaging features have not been previously described.

Case Report: A 66-year-old man with a recent diagnosis of classic Hodgkin lymphoma was referred to neuro-oncology for cognitive and motor decline, and progressive cerebral white matter changes noted on magnetic resonance imaging (MRI).

SOHO State of the Art Updates and Next Questions | From Biology to Therapy: Progress in Hodgkin Lymphoma.

Classic Hodgkin lymphoma (HL) is a unique lymphoid malignancy where the malignant cells comprise only 1% to 2% of the total tumor cellularity. Over the past 2 decades, the treatment of HL has evolved drastically based on the advent of novel targeted therapies. Novel agents including programmed death-1 (PD-1) inhibitors, antibody-drug conjugates such as brentuximab vedotin, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapies have served to shape the management of HL in the frontline as well as the relapsed and refractory (R/R) setting.

Symptoms and disease severity in lung transplant candidates co-managed with palliative care.

Background: Lung transplant (LTx) candidates experience significant respiratory symptoms often necessitating palliative care (PC) support. We aimed to describe symptoms experienced by interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) LTx candidates referred for PC using the Edmonton Symptom Assessment System (ESAS) and to assess the change in ESAS in relation to pre-LTx exercise capacity, oxygen requirements, and respiratory exacerbations. Understanding symptom trajectory of these two patient groups will help inform PC management.

CAR-T Cell Therapy: the Efficacy and Toxicity Balance.

Purpose Of Review: Chimeric antigen receptor (CAR) T cell therapy is an immunotherapy that has resulted in tremendous progress in the treatment of patients with B cell malignancies. However, the remarkable efficacy of therapy is not without significant safety concerns. Herein, we will review the unique and potentially life-threatening toxicities associated with CAR-T cell therapy and their association with treatment efficacy.

Survival trends in young patients with Waldenström macroglobulinemia: Over five decades of experience.

Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.

Computed tomography-based body composition measures in COPD and their association with clinical outcomes: A systematic review.

Background: Computed tomography (CT) is commonly utilized in chronic obstructive pulmonary disease (COPD) for lung cancer screening and emphysema characterization. Computed tomography-morphometric analysis of body composition (muscle mass and adiposity) has gained increased recognition as a marker of disease severity and prognosis. This systematic review aimed to describe the CT-methodology used to assess body composition and identify the association of body composition measures and disease severity, health-related quality of life (HRQL), cardiometabolic risk factors, respiratory exacerbations, and survival in patients with COPD.

Insurance-based disparities impact survival outcomes in Waldenström macroglobulinemia within the United States.

Considerable healthcare resource utilization and financial burden have been associated with the treatment of WM; however, the impact of health insurance status on outcomes has not been previously reported. We conducted a National Cancer Database analysis of newly diagnosed cases of active WM between 2004 and 2017 to evaluate the impact of insurance status on outcomes. For patients <65 years old ( = 1249, male sex: 62.

A real-world study of combined modality therapy for early-stage Hodgkin lymphoma: too little treatment impacts outcome.

Multiple clinical trials have assessed de-escalation strategies from combined modality therapy (CMT) to chemotherapy-alone for the treatment of early-stage classical Hodgkin lymphoma (cHL), confirming similar outcomes. The application of these data to the real-world is limited, however. We conducted a retrospective, multicenter cohort study comparing CMT vs chemotherapy-alone in patients with early-stage cHL (stage IA-IIB) treated between January 2010 and December 2020.

Current salvage therapies in Hodgkin lymphoma.

Hodgkin lymphoma is a B-cell malignancy with approximately 85-95% complete remission rate following frontline therapy; however, relapsed/refractory disease occurs in roughly 10-30% of patients after treatment. Salvage therapy conventionally relies upon cytotoxic chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation. A considerable number of patients experience relapse after transplantation, and further salvage management has included the use of allogeneic transplantation and radiotherapy.

Feasibility and Outcomes of a Standardized Management Protocol for Acute Exacerbation of Interstitial Lung Disease.

Background And Objective: Despite the high mortality of acute exacerbations of interstitial lung disease (AE-ILD), there is minimal evidence to guide management decisions. We aimed to assess the feasibility and outcomes of a standardized management protocol for AE-ILD.

Methods: We performed a retrospective cohort study of patients with AE-ILD admitted to hospital between January 2015 and August 2019.

A review of respiratory manifestations and their management in Ehlers-Danlos syndromes and hypermobility spectrum disorders.

Background: Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD) are a heterogeneous group of heritable genetic connective tissue disorders with multiple characteristics including joint hypermobility, tissue fragility, and multiple organ dysfunction. Respiratory manifestations have been described in EDS patients, but have not been systematically characterized. A narrative review was undertaken to describe the respiratory presentations and management strategies of individuals with EDS and HSD.

Clinical outcomes associated with computed tomography-based body composition measures in lung transplantation: a systematic review.

Computed tomography (CT) is gaining increased recognition in the assessment of body composition in lung transplant (LTx) candidates as a prognostic marker of post-transplant outcomes. This systematic review was conducted to describe the methodology of CT measures of body composition used in LTx patients and its association with post-transplant outcomes. Six databases were searched (inception-April 2020) for studies of adult LTx patients with thoracic or abdominal CT measures [muscle cross-sectional area (CSA) and/or adiposity].

Evaluation of Malnutrition Risk in Lung Transplant Candidates Using the Nutritional Risk Index.

Background: Malnutrition in lung transplant (LTx) candidates is an important risk factor for adverse outcomes. We sought to evaluate the Nutritional Risk Index (NRI) in LTx candidates, a validated measure of malnutrition risk in chronic disease. We aimed to characterize malnutrition risk using NRI, evaluate change in body weight between nutritional risk groups, and assess association of malnutrition risk with pretransplant and posttransplant outcomes.

A functionalized hydroxydopamine quinone links thiol modification to neuronal cell death.

Recent findings suggest that dopamine oxidation contributes to the development of Parkinson's disease (PD); however, the mechanistic details remain elusive. Here, we compare 6-hydroxydopamine (6-OHDA), a product of dopamine oxidation that commonly induces dopaminergic neurodegeneration in laboratory animals, with a synthetic alkyne-functionalized 6-OHDA variant. This synthetic molecule provides insights into the reactivity of quinone and neuromelanin formation.

Systematic review and meta-analysis of randomized controlled trials on the role of mometasone in adenoid hypertrophy in children.

Objectives: Mometasone has been reported to improve the symptoms of nasal obstruction in children with adenoidal hypertrophy. This systematic review and meta-analysis were conducted to evaluate the role of mometasone on different nasal symptoms, otitis media with effusion, adenoid size, and quality of life in children with adenoidal hypertrophy.

Methods: A comprehensive search of MEDLINE, EMBASE, CINAHL and COCHRANE Collaboration databases was undertaken.