Optimized monitoring for immune checkpoint inhibitor induced myocarditis using high-sensitivity troponin-T.

Background: Immune checkpoint inhibitor (ICI)-induced Myocarditis (irMyocarditis) is a rare adverse event with a high mortality rate of 40-50 % and which is mostly not diagnosed until clinical symptoms emerge.

Objectives: This study aims to screen patients for irMyocarditis using high-sensitivity cardiac troponin-T (hs-TnT) before and regularly during therapy with ICI.

Methods: A cohort of 280 cancer patients were prospectively screened for levels of hs-TnT at baseline and prior to every ICI infusion.

Stringent monitoring can decrease mortality of immune checkpoint inhibitor induced cardiotoxicity.

Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed.

Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.

Transforming growth factor β (TGF-β) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-β remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-β in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-β.

Reconfiguration and loss of peritubular capillaries in chronic kidney disease.

Functional and structural alterations of peritubular capillaries (PTCs) are a major determinant of chronic kidney disease (CKD). Using a software-based algorithm for semiautomatic segmentation and morphometric quantification, this study analyzes alterations of PTC shape associated with chronic tubulointerstitial injury in three mouse models and in human biopsies. In normal kidney tissue PTC shape was predominantly elongated, whereas the majority of PTCs associated with chronic tubulointerstitial injury had a rounder shape.

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy.

Chimeric antigen receptor (CAR) T cells targeting CD19 B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion.

Amelioration of Fibrotic Remodeling of Human 3-Dimensional Full-Thickness Skin by Transglutamase 2 Inhibition.

Objective: Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts.

The Exciting Future for Scleroderma: What Therapeutic Pathways Are on the Horizon?

Emerging evidence shows that a complex interplay between cells and mediators and extracellular matrix factors may underlie the development and persistence of fibrosis in systemic sclerosis. Similar processes may determine vasculopathy. This article reviews recent progress in understanding how fibrosis becomes profibrotic and how the immune system, vascular, and mesenchymal compartment affect disease development.

Rapid single-cell physical phenotyping of mechanically dissociated tissue biopsies.

During surgery, rapid and accurate histopathological diagnosis is essential for clinical decision making. Yet the prevalent method of intra-operative consultation pathology is intensive in time, labour and costs, and requires the expertise of trained pathologists. Here we show that biopsy samples can be analysed within 30 min by sequentially assessing the physical phenotypes of singularized suspended cells dissociated from the tissues.

Overuse-Related Injuries of the Knee.

Overuse-related injuries of the knee joint and periarticular soft tissues include a heterogenous group of sports and nonsports-related injuries. These conditions include friction and impingement syndromes, bone stress injuries, bursitis, and tendon-related pathology such as tendinopathy and snapping. Traction apophysitis are also discussed as commonly seen in the pediatric population.

Crystal arthropathies and osteoarthritis-where is the link?

Osteoarthritis (OA) is one of the leading causes of disability worldwide. As our understanding of OA progressively has moved from a purely mechanical "wear and tear" concept toward a complex multi-tissue condition in which inflammation plays a central role, the possible role of crystal-induced inflammation in OA incidence and progression may be relevant. In addition to gout, which affects 4% of the US population, basic calcium phosphate and calcium pyrophosphate deposition both may induce joint inflammation and may play a role in pain in OA.

PET Imaging in Osteoarthritis.

Osteoarthritis is a common cause of pain and morbidity resulting in heavy economic burden and large societal costs. Although cross-sectional imaging and in particular MR imaging have largely contributed to a better understanding of the complexity of this complex disease, especially in large joints such as the hip and knee joints, metabolic information of the subchondral bone and periarticular synovial environment has been consistently suggested to provide valuable supplemental information to morphologic and compositional MR imaging. The aim of this narrative review is to provide an overview of the role of the hybrid PET imaging in osteoarthritis with particular focus on PET/MR imaging.

Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages.

To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro-regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFα and IL-1β, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages.

Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis.

Background: Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc).

Methods: The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation.

Whole-body magnetic resonance imaging plus serological follow-up for early identification of progression in smouldering myeloma patients to prevent development of end-organ damage.

The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end-organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end-organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.

Purinergic signalling in systemic sclerosis.

SSc is a chronic autoimmune rheumatic disease that involves numerous organs and presents major management challenges. The histopathologic hallmarks of SSc include vasculopathy, fibrosis and autoimmune phenomena involving both innate and adaptive immune systems. Purinergic signalling is a pathway that may be implicated in the pathophysiology of several of these disease manifestations.

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease.

Acute graft versus host disease (aGvHD) is an important, life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). To investigate the value of multiple simultaneous colon biopsies in improving diagnostic accuracy in patients with aGvHD, we retrospectively analyzed 157 patients after alloHSCT. The biopsies were evaluated individually using three established histological grading systems (Lerner, Sale, and Melson).

TGFβ promotes fibrosis by MYST1-dependent epigenetic regulation of autophagy.

Activation of fibroblasts is essential for physiological tissue repair. Uncontrolled activation of fibroblasts, however, may lead to tissue fibrosis with organ dysfunction. Although several pathways capable of promoting fibroblast activation and tissue repair have been identified, their interplay in the context of chronic fibrotic diseases remains incompletely understood.

Human CD4 T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential.

Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells.

Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial.

Background: In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, nintedanib reduced the rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Patients on stable treatment with mycophenolate for at least 6 months before randomisation could participate. The aim of this subgroup analysis was to examine the efficacy and safety of nintedanib by mycophenolate use at baseline.

CytoResc - "CytoSorb" Rescue for critically ill patients undergoing the COVID-19 Cytokine Storm: A structured summary of a study protocol for a randomized controlled trial.

Objectives: Approximately 8 - 10 % of COVID-19 patients present with a serious clinical course and need for hospitalization, 8% of hospitalized patients need ICU-treatment. Currently, no causal therapy is available and treatment is purely supportive. The main reason for death in critically ill patients is acute respiratory failure.

Shared and distinct mechanisms of fibrosis.

Fibrosis is defined as an excessive deposition of connective tissue components and can affect virtually every organ system, including the skin, lungs, liver and kidney. Fibrotic tissue remodelling often leads to organ malfunction and is commonly associated with high morbidity and mortality. The medical need for effective antifibrotic therapies is thus very high.

Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?

Osteoarthritis (OA) of the hip and knee is among the most common joint disorders. Intra-articular corticosteroid (IACS) injections are frequently performed to treat OA and other joint-related pain syndromes; however, there is conflicting evidence on their potential benefit. There is a lack of prospective and large retrospective studies evaluating potential joint findings, including increased risk for accelerated OA progression or adverse joint events, after treatment with IACS injection.

Rationale for the evaluation of nintedanib as a treatment for systemic sclerosis-associated interstitial lung disease.

Interstitial lung disease is a common manifestation of systemic sclerosis. Systemic sclerosis-associated interstitial lung disease is characterized by progressive pulmonary fibrosis and a reduction in pulmonary function. Effective treatments for systemic sclerosis-associated interstitial lung disease are lacking.