Evaluating methods for integrating single-cell data and genetics to understand inflammatory disease complexity.

Background: Understanding genetic underpinnings of immune-mediated inflammatory diseases is crucial to improve treatments. Single-cell RNA sequencing (scRNA-seq) identifies cell states expanded in disease, but often overlooks genetic causality due to cost and small genotyping cohorts. Conversely, large genome-wide association studies (GWAS) are commonly accessible.

Predictive Value of Right Ventricular Sensing During Cardiac Device Implantation to Diagnose Cardiac Amyloidosis.

Background: Cardiac amyloidosis (CA) is an underdiagnosed disease, often presenting with electrical conduction abnormalities or ventricular arrhythmias, prompting implantation of cardiac implantable electrical devices (CIEDs).

Objectives: This study sought to evaluate the performance of right ventricular sensing (RVSens) during implantation of CIEDs in patients presenting with increased left ventricular (LV) wall thicknesses (ILVWT) and preserved LV function to predict the diagnosis of CA.

Methods: All consecutive patients with ILVWT (maximal LV wall thickness ≥12 mm), preserved LV function and no significant aortic stenosis who underwent implantation of CIEDs at 2 French referral centers for rare and inheritable cardiac diseases were retrospectively evaluated.

Improving genetic testing pathways for transthyretin amyloidosis in France: challenges and strategies.

Transthyretin amyloidosis (ATTR) is a severe and rare disease characterized by the progressive deposition of misfolded transthyretin proteins, causing irreversible organ damage. Transthyretin amyloidosis can present as a hereditary ATTR or acquired wild-type ATTR form. Genetic testing is critical for determining a hereditary predisposition and subsequently initiating appropriate family screening.

Clinical outcomes for 2788 patients with transthyretin amyloidosis: Tafamidis meglumine early access program in France.

Background: Early access experience in France with tafamidis meglumine, a selective transthyretin stabilizer for transthyretin-related amyloidosis cardiomyopathy (ATTR-CM), following transthyretin-related amyloidosis (ATTR) polyneuropathy approval and positive ATTR-ACT study results.

Aim: To describe the characteristics and clinical outcomes for patients in the French ATTR-CM tafamidis meglumine early access programme (28 Nov 2018 to 01 Jun 2021).

Methods: Patients with confirmed ATTR-CM received tafamidis meglumine 20mg/day or 80mg/day.

Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response.

Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe.

Axillary and subclavian venous spasm during pacemaker implantation - A case report and literature review.

Key Clinical Message: Venous spasm is an important reason for complicated or failed implantations of cardiac implantable electronic devices. Prevention or risk reduction of venous spasm during cardiac implantable electronic device implantation may be achieved by ultrasound or fluoroscopic imaging prior to puncture, cephalic vein cut-down, sufficient pre- and perioperative hydration, nitroglycerin injection and effective sedation, and analgesia.

Abstract: This case report with literature review focuses on venous spasm as a potential cause for complicated implantations of cardiac implantable electronic devices.

Comparison between remotely supported nurse-led electro-anatomic mapping and standard onsite engineer support for electrophysiological procedures.

Aims: Catheter ablations of complex cardiac arrhythmias are currently guided by electro-anatomic mapping (EAM) systems. The aim of this study was to compare two different approaches: remotely supported nurse-led EAM with standard onsite engineer support.

Methods And Results: In this retrospective observational study, 166 patients with complex and non-complex procedures were included.

Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms.

Alternative splicing events are a major causal mechanism for complex traits, but they have been understudied due to the limitation of short-read sequencing. Here, we generate a full-length isoform annotation of human immune cells from an individual by long-read sequencing for 29 cell subsets. This contains a number of unannotated transcripts and isoforms such as a read-through transcript of TOMM40-APOE in the Alzheimer's disease locus.

Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

Objective: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg.

Methods: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance.

Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis.

Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response.

Uncovering the Localization and Function of a Novel Read-Through Transcript ''.

Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, . With cDNA amplification from THP-1 cells, the product was successfully generated.

Impact of Previous Continuous Positive Airway Pressure Use on Noninvasive Ventilation Adherence and Quality in Obesity Hypoventilation Syndrome: A Pragmatic Single-Center Cross-Sectional Study in Martinique.

There is a strong relationship between obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). When OHS is combined with severe OSA, treatment consists of continuous positive airway pressure (CPAP), followed by noninvasive ventilation (NIV) in the case of CPAP failure. Currently, the impact of a previous use of CPAP on the quality of NIV is unknown.

Frequency and Distribution of Broncho-Alveolar Fungi in Lung Diseases in Martinique.

The microbiota refers to all the microorganisms living in and on the human body; its fungal component is known as the mycobiota. The molecular component (mycobiome) has been linked to certain pulmonary diseases. Morphological fungal examination is still common practice and makes it possible to isolate fungi on direct examination or after sample culture.

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in 'At-Risk' populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48).

Risk Stratification in Transthyretin Cardiac Amyloidosis: The Added Value of Lung Spirometry.

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death.

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity.

The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise.

Association between Previous CPAP and Comorbidities at Diagnosis of Obesity-Hypoventilation Syndrome Associated with Obstructive Sleep Apnea: A Comparative Retrospective Observational Study.

Obesity-hypoventilation syndrome (OHS) is associated with many comorbidities. The aim of this study was to evaluate the association between previous continuous positive airway pressure (CPAP) and the prevalence of comorbidities in OHS associated with obstructive sleep apnea (OSA). We performed a retrospective, single-center study at the University Hospital of Martinique, the referral hospital for the island of Martinique.

Single-cell computational machine learning approaches to immune-mediated inflammatory disease: New tools uncover novel fibroblast and macrophage interactions driving pathogenesis.

Recent advances in single-cell sequencing technologies call for greater computational scalability and sensitivity to analytically decompose diseased tissues and expose meaningful biological relevance in individual cells with high resolution. And while fibroblasts, one of the most abundant cell types in tissues, were long thought to display relative homogeneity, recent analytical and technical advances in single-cell sequencing have exposed wide variation and sub-phenotypes of fibroblasts of potential and apparent clinical significance to inflammatory diseases. Alongside anticipated improvements in single cell spatial sequencing resolution, new computational biology techniques have formed the technical backbone when exploring fibroblast heterogeneity.