Dual transcatheter edge-to-edge repair in a patient with cardiac amyloidosis and severe secondary mitral and tricuspid regurgitation: a case report.

Background: Mitral and tricuspid regurgitation in patients with cardiac amyloidosis (CA) pose significant diagnostic and therapeutic challenges due to its non-specific symptoms and limited treatment options. Transcatheter edge-to-edge repair (TEER) is complicated by altered cardiac geometry, advanced restriction, and potential amyloid valve deposits.

Case Summary: We present the case of dual TEER in a 79-year-old male with advanced transthyretin cardiac amyloidosis (ATTR-CA) and severe symptomatic mitral and tricuspid regurgitation.

Association between education level and access to disease-modifying treatment in patients with multiple sclerosis in France.

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).

Objective: This study aimed to analyze the association between education level and DMT use in France.

Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included.

Return of individual genomic research results within the PRAEGNANT multicenter registry study.

Purpose: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

Background And Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

Occurrence and characteristics of patients with de novo advanced breast cancer according to patient and tumor characteristics - A retrospective analysis of a real world registry.

Background: Patients with de novo metastatic breast cancer (dnMBC) may have different clinical and pathological characteristics. In studies concerned with first-line metastatic patients, the proportion of these patients without secondary resistance mechanisms may have a large influence ont the study results. The aim of this study was to identify patient and tumor characteristics that are associated with dnMBC vs.

Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison.

Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain.

Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA).

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Steroid-Peptide Immunoconjugates for Attenuating T Cell Responses in an Experimental Autoimmune Encephalomyelitis Murine Model of Multiple Sclerosis.

Diseases of immunity, including autoimmune diseases such as multiple sclerosis, transplantation graft rejection, allergy, and asthma, are prevalent and increasing in prevalence. They contribute to significant morbidity and mortality; however, few if any curative therapies exist, and those that are available lack either potency or specificity. Dendritic cells (DCs) are sentinels of the immune system that connect the innate and adaptive immune system and are critical regulators of both immunity and tolerance.

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting.

Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure.

Background: The cyclic AMP (adenosine monophosphate; cAMP)-hydrolyzing protein PDE4B (phosphodiesterase 4B) is a key negative regulator of cardiac β-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal Ca handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure.

Methods: We measured PDE4B expression in human cardiac tissues and developed 2 transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B and an adeno-associated virus serotype 9 encoding PDE4B.

Risk of Hypersensitivity Reactions to Iopromide After Intra-Arterial Versus Intravenous Administration: A Nested Case-Control Analysis of 133,331 Patients.

Objective: The aim of this study was to compare the risk of hypersensitivity reactions to iopromide after intra-arterial (IA) administration and intravenous (IV) administration.

Materials And Methods: Four observational studies were pooled. Almost half of the study population (48.

Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis.

Objective: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.

Methods: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation.

Coinhibitory suppression of T cell activation by CD40 protects against obesity and adipose tissue inflammation in mice.

Background: Costimulatory cascades such as the CD40L-CD40 dyad enhance immune cell activation and inflammation during atherosclerosis. Here, we tested the hypothesis that CD40 directly modulates traits of the metabolic syndrome in diet-induced obesity in mice.

Methods And Results: To induce the metabolic syndrome, wild-type or CD40(-/-) mice consumed a high-fat diet for 20 weeks.

An evolution model for sequence length based on residue insertion-deletion independent of substitution: an application to the GC content in bacterial genomes.

We introduce here a gene evolution model which is an extension of the time-continuous stochastic IDIS model (Lèbre and Michel in J. Comput. Biol.

Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics.

Aims: A radioreceptor assay has been developed for alpha1-adrenoceptor subtypes and applied to a pharmacokinetic analysis of tamsulosin and terazosin.

Methods: Young, male, healthy volunteers received 0.4 mg tamsulosin (as Omnic modified release capsules) or 5 mg terazosin (as Flotrin tablets) in a randomized, cross-over design.

Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat.

The metabolism of atrial natriuretic peptide (ANP) and Cys-105-Phe-106-cleaved ANP (ANP) was studied during constant infusion of 125I-labelled peptides in rats. Analysis of circulating radioactivity indicated rapid clearance of ANP and ANP', with mean half-lives of 0.42 and 1.