Circulating ECM proteins decorin and alpha-L-iduronidase differentiate ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF.

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights.

[Tc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

Purpose: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality.

ELISA-4-amyloid: diagnostic accuracy of an ELISA panel for typing the four main types of systemic amyloidosis in subcutaneous abdominal fat tissue samples.

Background: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA).

Objective: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid).

Baseline Blood CD8 T Cell Activation Potency Discriminates Responders from Non-Responders to Immune Checkpoint Inhibition Combined with Stereotactic Radiotherapy in Non-Small-Cell Lung Cancer.

Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells may predict response to ICI treatment.

Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.

Objective: To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and variant (v) carriers.

Methods: sNfL levels were assessed longitudinally in persistently asymptomatic v carriers ( = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) ( = 8), in v carriers who developed polyneuropathy ( = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser ( = 20) or TTR-silencer ( = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing.

Metabolic Dysfunction-Associated Steatotic Liver Disease in a Dish: Human Precision-Cut Liver Slices as a Platform for Drug Screening and Interventions.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing healthcare problem with limited therapeutic options. Progress in this field depends on the availability of reliable preclinical models. Human precision-cut liver slices (PCLSs) have been employed to replicate the initiation of MASLD, but a comprehensive investigation into MASLD progression is still missing.

High-Sensitivity Cardiac Troponin T to Exclude Cardiac Involvement in TTR Variant Carriers and ATTRv Amyloidosis Patients.

(1) Background: Individuals carrying a pathogenic transthyretin gene variant () are at high risk for developing hereditary transthyretin (ATTRv) amyloidosis and are routinely screened for the development of cardiomyopathy (ATTRv-CM). This study aims to evaluate whether the cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can be used to rule out ATTRv-CM. (2) Methods: In this retrospective case-control study, data from 46 ATTRv-CM patients and 101 carriers and ATTRv amyloidosis patients without cardiomyopathy were included.

Cardiac [Tc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

Purpose: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments.

Methods: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer.

The Protein Network in Subcutaneous Fat Biopsies from Patients with AL Amyloidosis: More Than Diagnosis?

AL amyloidosis is caused by the misfolding of immunoglobulin light chains leading to an impaired function of tissues and organs in which they accumulate. Due to the paucity of -omics profiles from undissected samples, few studies have addressed amyloid-related damage system wide. To fill this gap, we evaluated proteome changes in the abdominal subcutaneous adipose tissue of patients affected by the AL isotypes and λ.

Circulating adipokine levels and COVID-19 severity in hospitalized patients.

Background: Obesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma adipokines and COVID-19 severity, systemic inflammation, clinical parameters, and outcome of COVID-19 patients.

Methods: In this multi-centre prospective cross-sectional study, we collected blood samples and clinical data from COVID-19 patients.

Amyloid fibril structure from the vascular variant of systemic AA amyloidosis.

Systemic AA amyloidosis is a debilitating protein misfolding disease in humans and animals. In humans, it occurs in two variants that are called 'vascular' and 'glomerular', depending on the main amyloid deposition site in the kidneys. Using cryo electron microscopy, we here show the amyloid fibril structure underlying the vascular disease variant.

Long-Term Stability of Blood Serum Biomarkers in Traumatic Brain Injury: A Feasibility Study.

Few studies on traumatic brain injury (TBI) have investigated the stability of blood serum biomarkers after long-term storage at low temperatures. In the current feasibility study we analyzed acute phase serum samples from patients with mild TBI as well as patients with moderate and severe TBI that were collected more than 10 years ago (). We were particularly interested in mild TBI, because injury effects are more subtle in this category as compared to moderate-severe TBI.

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis.

Objectives: GCA is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with 18F-fluorodeoxyglucose ([18F]FDG)-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA.

Protease resistance of amyloid fibrils implies the proteolytic selection of disease-associated fibril morphologies.

Several studies recently showed that fibrils from patient or animal tissue were structurally different from formed fibrils from the same polypeptide chain. Analysis of serum amyloid A (SAA) and Aβ-derived amyloid fibrils additionally revealed that fibrils were more protease stable than fibrils. These observations gave rise to the proteolytic selection hypothesis that suggested that disease-associated amyloid fibrils were selected inside the body by their ability to resist endogenous clearance mechanisms.

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis.

Objective: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP.

Methods: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin ( gene mutation carriers (v carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and v carriers (HC/v).

A real-life cohort study of immunoglobulin light-chain (AL) amyloidosis patients ineligible for autologous stem cell transplantation due to severe cardiac involvement or advanced disease.

To study the outcome of patients with AL amyloidosis who were ineligible for high dose melphalan (HDM) and autologous stem cell transplantation (ASCT). A real-life retrospective observational cohort study of Dutch patients with AL amyloidosis ineligible for HDM and ASCT was performed at the University Medical Center Groningen from January 2001 until April 2017. Primary outcome measure was overall survival (OS).

Causes of AA amyloidosis: a systematic review.

From a clinical perspective, there is a need for a reliable and comprehensive list of diseases causing AA amyloidosis. This list could guide clinicians in the evaluation of patients with AA amyloidosis in whom an obvious cause is lacking. In this systematic review, a PubMed, Embase and Web of Science literature search were performed on causes of AA amyloidosis published in the last four decades.

High angiopoietin-2 levels associate with arterial inflammation and long-term glucocorticoid requirement in polymyalgia rheumatica.

Objectives: PMR frequently co-occurs with GCA. So far, a simple biomarker for detecting concomitant arterial inflammation in PMR patients is lacking. Furthermore, biomarkers predicting disease course in PMR are awaited.

Morphological and primary structural consistency of fibrils from different AA patients (common variant).

To test the hypothesis that the fibril morphology and the fibril protein primary structure are conserved across different patients suffering from the common variant of systemic Amyloid A AA) amyloidosis. Amyloid fibrils were extracted from the renal tissue of four patients. The fibril morphology was analysed in negatively stained samples with transmission electron microscopy (TEM).