Protamine avoidance

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects...

B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos...

BACKGROUND: Infants < 10 kg undergoing cardiac surgery with cardiopulmonary bypass (CPB) may receive either fresh frozen plasma (FFP) or other solutions in the CPB priming volume. The existing comparative studies are controversial. No study addressed the possibility of total avoidance of FFP throughout the whole perioperative course in this patient population. This retrospective, non-inferiority, propensity-matched study investigates an FFP-free strategy compared to an FFP-based strategy...

Unique chromatin remodeling factors orchestrate dramatic changes in nuclear morphology during differentiation of the mature sperm head. A critical step in this process is histone-to-protamine exchange, which must be executed correctly to avoid sperm DNA damage, embryonic lethality, and male sterility. Here, we define an essential role for the histone methyltransferase DOT1L in the histone-to-protamine transition. We show that DOT1L is abundantly expressed in meiotic and postmeiotic germ cells and that methylation of histone H3 lysine 79 (H3K79), the modification catalyzed by DOT1L, is enriched in developing spermatids in the initial stages of histone replacement...

INTRODUCTION: Pericardial bleeding is a rare but life-threatening complication of atrial fibrillation (AF) ablation. Patients taking uninterrupted oral anticoagulation (AC) may be at increased risk for refractory bleeding despite pericardiocentesis and administration of protamine. In such cases, andexanet alfa can be given to reverse rivaroxaban or apixaban. In this study, we aim to describe the rate of acute hemostasis and thromboembolic complications with andexanet for refractory pericardial bleeding during AF ablation...

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system adapted from bacteria is a programmable nuclease-based genome editing tool. The long-lasting effect of gene silencing or correction is beneficial in cancer treatment. Considering the need to broaden the practical application of this technology, highly efficient non-viral vectors are urgently required. We prepared a multifunctional non-viral vector that could actively target tumor cells and deliver CRISPR/Cas9 plasmids into nuclei of cancer cells...

BACKGROUND: Despite many patients undergoing carotid endarterectomy (CEA) being on dual antiplatelet therapy (DAPT) for cardiac or neurologic indications, the impact of such therapy on perioperative outcomes remains unclear. We aim to compare rates of postoperative bleeding, stroke and major adverse events (stroke, death or MI) among patients on Aspirin alone (ASAA) versus DAPT (Clopidogrel and Aspirin). METHODS: Patients undergoing CEA for carotid artery stenosis between 2010 and 2021 in the Vascular Quality Initiative (VQI) were included...

Purpose of Review: Allergy to excipients is a cause of multidrug allergy and if it is not taken into account, it can lead to unexpected severe reactions. If an excipient allergy is suspected, an accurate examination followed by algorithms is very important for a correct diagnosis and to give patients detailed information in order to avoid future reactions. Recent Findings: In recent times, due to allergy COVID vaccine reactions, interest in excipients as polyethylene glycol derivatives (PEGs) has increased as a possible cause of drug and vaccine hypersensivity...

The development of nanovectors for precise gene therapy is increasingly focusing on avoiding uncontrolled inflammation while still being able to effectively act on the target sites. Herein, we explore the use of non-viral hybrid polyelectrolyte nanocomplexes (hPECs) for gene delivery, which display good transfection efficacy coupled with non-inflammatory properties. Monodisperse hPECs were produced through a layer-by-layer self-assembling of biocompatible and biodegradable polymers. The resulting nanocomplexes had an inner core characterized by an EGFP-encoding plasmid DNA (pDNA) complexed with linear polyethyleneimine or protamine (PEI or PRM) stabilized with lecithin and poly(vinyl alcohol) (PVA) and an outer layer consisting of medium-molecular-weight chitosan (CH) combined with tripolyphosphate (TPP)...

BACKGROUND: Despite continued efforts to improve the safety of catheter ablation, pericardial tamponade remains one of its more frequent, potentially life-threatening complications. Management of cardiac tamponade is not standardized and uncertainties regarding acute treatment remain. METHODS: This survey sought to evaluate the management of cardiac tamponade in German EP centers via a standardized postal questionnaire. All 341 identified German EP centers were invited to return a questionnaire on their standards for the management of cardiac tamponade...

BACKGROUND: Pseudothrombocytopenia is a phenomenon caused by in vitro platelet aggregation induced by anticoagulants contained in blood sampling tubes. Thromboelastography (TEG) 6s is a common point-of-care viscoelastic test to assess intraoperative coagulation status, which may reduce the need for blood transfusions. The reliability and usefulness of TEG6s for patients with pseudothrombocytopenia has not been established. CASE PRESENTATION: We present a patient with pseudothrombocytopenia, who underwent suprarenal abdominal aortic aneurysm repair under cardiopulmonary bypass...

To quantify the urinary bladder wall T1 relaxation time (T1 ) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol...

BACKGROUND: Severe bleeding under antithrombotic therapy is common and challenging in intensive care medicine; on the one hand, rapid bleeding control must be achieved and, on the other hand, thromboembolic complications must be avoided. AIMS: The paper will provide a brief overview of direct oral anticoagulants, therapeutic options and precise instructions for dealing with severe bleeding. RESULTS: In addition to general measures in direct oral anticoagulant (DOAC)-associated major bleeding, prothrombin complex concentrate (PCC), idarucizumab and andexanet alfa are available as specific antidote therapy...

BACKGROUND: Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM)...

Unfractionated heparin (UFH) is an anionic glycosaminoglycan that is widely used to prevent blood clotting. However, in certain cases, unwanted side effects can require it to be neutralized. Protamine sulfate (PS), a basic peptide rich in arginine, is the only approved antagonist for UFH neutralization. Many adverse reactions occur with the clinical application of PS, including systemic hypotension, pulmonary hypertension, and anaphylaxis. We previously described R15, a linear peptide composed of 15 arginine molecules, as a potential UFH antagonist...

BACKGROUND: An 82-year-old female with a history of atrial fibrillation and repeated episodes of major bleeding on direct oral anticoagulant therapy, with a high risk for thromboembolism and was referred for left atrial appendage closure. CASE SUMMARY: During the procedure, an unrecognized puncture of the aorta by the transseptal puncture (TSP) needle and inadvertent advancement of the sheath resulted in ascending aorta perforation. This perforation was closed percutaneously using an Amplatzer™ Duct Occluder (ADO)...

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine sparing effects-but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation...

Resistance to platinum agents is a crucial challenge in the treatment of cancer using platinum drugs. To overcome the resistance of cells, the survivin protein is supposed to be decreased, since it has previously been found to be overexpressed in drug-resistant cancer cells in anti-apoptosis pathways, while the intracellular effective platinum accumulation should be increased. In the present work, a protamine/hyaluronic acid nanocarrier was used to load survivin siRNA with Pt(IV) loaded outside the coated polyglutamic acid (PGA) by chemical conjugation...

INTRODUCTION: We describe how to perform left internal mammary artery (LIMA) bypass to the left anterior descending (LAD) artery, the so-called MINI Off-pump Coronary Artery Bypass (MINI OPCAB). MATERIALS AND METHODS: We included patients with a demonstrated predominant ischemia related to the LAD territory. Of 70 patients who were operated upon at the Benetti Foundation, 10 received hybrid revascularization. SURGICAL TECHNIQUE: The patient is prepared as for a standard coronary bypass operation through sternotomy...

BACKGROUND: In this study, the effects of pulsatile and non-pulsatile on-pump Coronary Artery Bypass Graft surgery (CABG) and off-pump CABG techniques on the intraocular pressure were investigated. METHODS: Forty-five patients who planned to elective coronary artery bypass surgery with on-pump pulsatile (n=15), non-pulsatile (n=15), or off-pump (n=15) were included. Intraocular Pressure (IOP) measurements were performed on both eyes at nine time-points: 1) Before the operation, 2) After anesthesia induction, 3) 3 minutes after heparin administration Left Internal Mammary Artery (LIMA) harvesting, 4) End of the first anastomosis, 5) End of LIMA anastomosis, 6) 3 minutes after protamine administration, 7) End of the operation, and 8) Second hour in Intensive Care Unit (ICU), 9) Fifth hour in ICU...