Therapeutic silencing in TREM2 cardiac macrophages suppresses atrial fibrillation.

Atrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2 macrophages secrete osteopontin (encoded by ), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencing in TREM2 cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia.

Refractory Autonomic Instability in Mild Traumatic Brain Injury: A Case Report.

Although the specific relationship between concussion and the autonomic nervous system (ANS) has not been fully elucidated, it is generally understood that the pathologic response after a traumatic brain injury (TBI) is linked with systolic cardiac dysfunction. In this case, we present a patient with multiple concussion injuries over a five-year period who exhibited severe cardiac and autonomic dysfunction, in addition to prolonged impairments in vestibular function, oculomotor function, cognitive function, and headaches. The patient is a 28-year-old male with a past medical history of multiple concussions, with the first concussion occurring due to a skiing accident in January 2015.

Bone marrow adipocytes fuel emergency hematopoiesis after myocardial infarction.

After myocardial infarction (MI), emergency hematopoiesis produces inflammatory myeloid cells that accelerate atherosclerosis and promote heart failure. Since the balance between glycolysis and mitochondrial metabolism regulates hematopoietic stem cell homeostasis, metabolic cues may influence emergency myelopoiesis. Here, we show in humans and female mice that hematopoietic progenitor cells increase fatty acid metabolism after MI.

Recruited macrophages elicit atrial fibrillation.

Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and macrophage expansion in atrial fibrillation.

A clinical study to evaluate the safe and effective use of a new, single use stethoscope cover to enable reduction in pathogen transmission during auscultation.

Objectives: Stethoscopes carry a significant risk for pathogen transmission. Here, the safe use and performance of a new, non-sterile, single-use stethoscope cover (SC), that is impermeable for pathogens, was investigated by different healthcare professionals (HCPs) in the postoperative care setting of an intensive care unit (ICU).

Methods: Fifty-four patients underwent routine auscultations with the use of the SC (Stethoglove, Stethoglove GmbH, Hamburg, Germany).

Use of the HemaClear™ elastic tourniquet reduces blood loss in operative treatment of humeral shaft fractures.

Background: To determine if the use of a narrower elastic tourniquet compared to a standard pneumatic tourniquet reduces operative blood loss in the operative fixation of humeral shaft fractures.

Methods: This retrospective cohort study was performed at a level I trauma center and included 134 patients, aged 18 to 90 years, with a humeral shaft fracture treated with open reduction internal fixation (ORIF) from January 2007 through June 2018. The primary variable of interest was the application of a HemaClear™ elastic tourniquet versus a standard pneumatic tourniquet during the fixation of a humeral shaft fracture.

Neutrophils incite and macrophages avert electrical storm after myocardial infarction.

Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction.

Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation.

Obesity is an important risk factor for atrial fibrillation (AF), but a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned within multiple obesity-related pathways, and prior work has shown a pathologic role of SGK1 signaling in ventricular arrhythmias. We validated a mouse model of obesity-related AF using wild-type mice fed a high-fat diet.

A Dorsal Epidural Herniated Disc Fragment Initially Presenting as Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is a rare autoimmune disorder that presents with neurological symptoms that can mimic other conditions. This mimicry can hide other important neurological diagnoses. Here, we present a rare case of thoracic myelopathy secondary to a sequestered dorsal epidural herniated disc fragment that initially presented with the classic findings of GBS.

Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease.

Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ's microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis.

Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis.

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues facilitate intersystem communication. Cerebrospinal fluid (CSF), which interfaces with the glymphatic system and thereby drains the brain's interstitial and perivascular spaces, facilitates outward signaling beyond the blood-brain barrier.

B lymphocyte-derived acetylcholine limits steady-state and emergency hematopoiesis.

Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate hematopoiesis is unclear. Here, we show that B lymphocytes are an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system, which reduced hematopoiesis.

Risk factors for treatment failure of fracture-related infections.

Objective: Infection after fracture fixation is a potentially devastating outcome, and surgical management is frequently unsuccessful at clearing these infections. The purpose of this study is to determine if factors can be identified that are associated with treatment failure after operative management of a deep surgical site infection.

Methods: We retrospectively reviewed the billing system at a Level I trauma center between March 2006 and December 2015.

Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis.

Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis.

Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase.

Background: Ibrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood.

Methods: We performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF.

Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche.

Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid-polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow.

Do Fully Threaded Transiliac-Transsacral Screws Improve Mechanical Stability of Vertically Unstable Pelvic Fractures? A Cadaveric Biomechanical Analysis.

Objective: To determine whether fully threaded transiliac-transsacral (TI-TS) fixation is biomechanically superior to partially threaded TI-TS fixation of vertically unstable transforaminal sacral fractures.

Methods: Vertically unstable zone 2 sacral fractures were created in 20 human cadaveric pelves with a unilateral osteotomy and resection of 1 cm of bone through the foramen of the sacrum to represent comminution. Ten specimens received either 2 7.

Association Between Femoral "Spike" Size After Intramedullary Nailing and Subsequent Knee Motion Surgery.

Objectives: To determine the association between displaced femoral shaft bone fragments ("spikes") seen on radiographs after intramedullary nail insertion and the need for future motion surgery.

Design: Retrospective case-control study.

Setting: Academic trauma center.

Posterolateral plating is a safe alternative for the treatment of distal tibial fractures.

Introduction: We assessed the outcome and safety of posterior plating of distal tibial fractures.

Methods: We conducted a retrospective case series at a Level I trauma center. Seventy-four consecutive patients with distal tibial fractures treated with anatomically contoured 3.

Modifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity.

Unhealthy diet, lack of exercise, psychosocial stress, and insufficient sleep are increasingly prevalent modifiable risk factors for cardiovascular disease. Accumulating evidence indicates that these risk factors may fuel chronic inflammatory processes that are active in atherosclerosis and lead to myocardial infarction and stroke. In concert with hyperlipidemia, maladaptive immune system activities can contribute to disease progression and increase the probability of adverse events.

Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes Mellitus.

Background: Diabetes mellitus is a prevalent public health problem that affects about one-third of the US population and leads to serious vascular complications with increased risk for coronary artery disease. How bone marrow hematopoiesis contributes to diabetes mellitus complications is incompletely understood. We investigated the role of bone marrow endothelial cells in diabetic regulation of inflammatory myeloid cell production.

Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction.

Background: Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism's response to secondary inflammatory challenges.

Objectives: This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation.