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Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.

Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibito

Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2018

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New drugs 09, part 2.

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Stridor in pediatric patients.

We have presented a classification scheme to help in evaluating the diagnosis of stridor in the pediatric patient. The correct diagnosis can usually be arrived at on the basis of a careful and complete history, physical examination, appropriate radiographic studies and bronchoscopy. The anesthesiologist should be aware of the problems associated with all these conditions. In every instance prompt establishment of an adequate airway is imperative.

Incidence of mucocutaneous reactions in children treated with niflumic acid, other nonsteroidal antiinflammatory drugs, or nonopioid analgesics.

BACKGROUND AND OBJECTIVE: Results from a relatively small case-control study recently showed that niflumic acid increases the risk of seriou … ferred) and mild mucocutaneous reactions (exanthema, disseminated or localized pruritus, urticaria, angioedema, fixed eruption, dermatitis, erythema multiforme, vesicles, bullae, pustules, toxic epidermal necrolysis, purpura, and vasculitis) was estimated during use of niflumic acid, other NSAIDs, or nonopioid analgesics. For each episode of drug use, the fo …

Angiotensin II receptor antagonists and heart failure: angiotensin-converting-enzyme inhibitors remain the first-line option.

(1) Some angiotensin-converting-enzyme inhibitors (ACE inhibitors) reduce mortality in patients with heart failure (captopril, enalapril, ra … certain serious adverse effects such as hyperkalemia, renal failure and hypotension. In one trial, angioedema was less frequent with angiotensin II receptor antagonist therapy (one less case per 500 patients).

Latex allergy in the workplace.

While less than 1% of the general population is sensitized to latex, the U.S. Occupational Safety and Health Administration estimates that 8 … itivity response. Type I (IgE-mediated) NRL allergy includes contact urticaria, systemic urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis. Taking an accurate history, including questions on atopic status, food allergy, and possible reactions to latex devices makes diagnosis of type-I latex allergy possible. To confirm a diagnosi …

Abdominal Pain Mimics.

Abdominal pain is a common reason for emergency department visits, with many patients not receiving a definitive diagnosis for their symptoms. Non-gastrointestinal causes need to be considered in the workup of abdominal pain. A high index of suspicion is needed in order to develop a broad differential, and a thorough history and physical examination is paramount. This article will discuss some of these diagnoses, including can't miss diagnoses, common non-abdominal causes, and rare etiologies of abdominal pain.

Tolerability of three selective cyclo-oxygenase-2 inhibitors, meloxicam, celecoxib and rofecoxib in NSAID-sensitive patients.

BACKGROUND: Patients with aspirin-sensitive respiratory and cutaneous diseases experience cross reactions to all nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclo-oxigenase (COX) enzymes. As are now available drugs which selectively inhibit COX-2, questions are raised whether cross-reactivity occurs between aspirin and these COX 2 inhibitors. OBJECTIVE: The aim of this study was to evaluate the tolerability of three COX-2 inhibitors (meloxicam, celecoxib and rofecoxib) in subjects with previous pseudoallergic respiratory and cutaneous reactions to NSAIDs. METHODS: 76 subjects

MR and CT angiography in the diagnosis of vasculitides.

Vasculitides represent the wide-ranging series of complex inflammatory diseases that involve inflammation of blood vessel walls. These conditions are characterized according to the caliber of the predominantly involved vessels. The work-up of vasculitides often includes imaging to narrow a differential diagnosis and guide management. Findings from CT and MR angiography in conjunction with a thorough history and physical exam are of utmost importance in making an accurate diagnosis. Further, imaging can be used for follow-up, in order to monitor disease progression and response to treatment. Th

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… Over of half of patients can be present with angioedema, often involving the facial area and upper extremities. 82,83 Although angioedema most commonly involves the face and upper extremities, other rarer presentations of angioedema may prove to be a difficult diagnosis. … Areas typically unaffected by angioedema such as the mediastinum and axial retroperitoneum were heavily implicated in these angioedema attacks. …

Do Antinuclear Antibodies Influence the Clinical Features of Chronic Spontaneous Urticaria?: A Retrospective Cohort Study.

BackgroundAntinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described.ObjectivesTo compare clinical features of CSU patients who are positive and negative for ANA.MethodsThis was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until

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… Some patients may also develop swelling of the tissue around the eyes and mouth (angioedema) [ 1 ]. CSU is the most common type of chronic urticaria with a prevalence of 0.5-1% of the population [ 2 ]. … A study by Magen et al. [ 24 ] reported no significant difference assessed by initial UAS and the prevalence of angioedema. In contrast, Ertaş et al. [ 21 ] reported a significantly higher prevalence of angioedema. …

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease.

Hematologic diseases include a broad range of acquired and congenital disorders, many of which affect plasma proteins that control hemostasis and immune responses. Therapeutic interventions for these disorders include transfusion of plasma, cryoprecipitate, immunoglobulins, or convalescent plasma-containing therapeutic antibodies from patients recovering from infectious diseases, as well as concentrated pro- or anticoagulant factors. This review will focus on recent advances in the uses of plasma and its derivatives for patients with acquired and congenital hematologic disorders.

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… C1 inhibitor Hereditary angioedema is a congenital deficiency or dysfunction of C1 esterase inhibitor (C1-INH). … The safety of treatments for angioedema with hereditary c1 inhibitor deficiency. Expert Opin Drug Saf. 2015;14(11):1725–1736. doi: 10.1517/14740338.2015.1094053. 176. Longhurst H, Zinser E. Prophylactic therapy for hereditary angioedema. …

Abstracts from the 8th Drug Hypersensitivity Meeting (DHM)

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The landscape and trajectory of global CRISPR therapeutics.

With the first regulatory approval in 2023 of a CRISPR-based therapy for sickle cell disease followed by the recent demonstration of an accelerated, personalized CRISPR treatment for congenital severe carbamoyl-phosphate synthetase 1 deficiency, CRISPR-Cas9 genome editing has progressed from a laboratory technology into a clinical reality in just over a decade. While enthusiasm for deploying CRISPR-Cas9 to treat a range of human genetic diseases continues to grow, broad clinical application remains constrained due to technical, regulatory, manufacturing and economic challenges. Here, scientist

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… Another EU trial evaluates NTLA-2002, a phase 2 CRISPR-based therapy for hereditary angioedema (HAE), which is also under investigation in the US. … Hereditary angioedema: new findings concerning symptoms, affected organs, and course Am. J. Med. 119 2006 267 274 10.1016/j.amjmed.2005.09.064 16490473 55 Zuraw B.L. Clinical practice. Hereditary angioedema N. Engl. J. Med. 359 2008 1027 1036 10.1056/NEJMcp0803977 18768946 56 Longhurst H.J. …

Allergy in Cancer Care: Antineoplastic Therapy-Induced Hypersensitivity Reactions.

As the backbone of oncological treatments, systemic chemotherapy is still one of the main pawns in cancer care, alone or in combination with newer targeted agents. All chemotherapy agents can be associated with a type of adverse event called an infusion reaction, which can be characterized as unpredictable, non-dose related, and unexplained by the cytotoxic profile of the drug. For some of these events, a certain immunological mechanism can be identified by blood or skin testing. In this case, we can speak of true hypersensitivity reactions that occur as a response to an antigen/allergen. The

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… Type I is IgE-mediated and consists of symptoms such as urticaria, angioedema, bronchospasm, and anaphylaxis. Type II involves the cytolytic antibodies (IgG or IgM), inducing hemolytic anemia. … Urticaria, angioedema, hypotension, and severe dyspnea can signal a type I allergic reaction to the administration of this monoclonal antibody. …

[Angiotensin-converting enzyme inhibitors. Principles and rules of use].

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Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas

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… Gene disruption technology to stop inflammatory disease In hereditary angioedema (HAE), individuals experience severe episodes of inflammation resulting in swelling, typically affecting the arms and legs, face, intestines, or airway. … Similar to hATTR, angioedema can be acquired but also may be inherited (Ref 111 ). NTLA-2002 is a CRISPR drug candidate developed by Intellia Therapeutics for HAE, intended to target the KLKB1 gene in liver cells to reduce kallikrein protein production (Ref 112 ). …

Allergy to beta-lactam antibiotics in children.

BACKGROUND: Skin tests with soluble beta-lactams can be used to diagnose immediate and delayed hypersensitivity (HS) reactions to beta-lacta … dermal and patch tests) have been reported in adult patients and children suffering with urticaria, angioedema, and maculopapular rashes during treatments with beta-lactam antibiotics. However, the diagnostic and predictive values of late responses are unknown. Semi-late responses in skin tests with beta-lactams have never been studied in adults or children. …

Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.

Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created c

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… In 2018, lanadelumab has received the US FDA approval for the prevention of the angioedema attacks in patients with hereditary angioedema. … Currently, it is being evaluated in two active phase III clinical trials to prevent hereditary angioedema attacks in pediatric patients as well as in adolescent and adult patients suffering from acquired angioedema (AAE) due to C1-INH deficiency ( NCT04070326 and NCT04206605 ). …

The potential of oral healthcare providers to recognise early systemic disease.

Like many other body structures, the mouth is often affected by disease that principally arises from, or targets, several tissue sites. Indeed, systemic disorders can manifest on the oral mucosa as the first, only, or become the most severe manifestation of a systemic disease and/or become the most significant factor to adversely affect an individual's quality of life. Oral healthcare providers (dentists, therapists and hygienists) may be the first to observe an abnormality in the mouth which sometimes indicates a significant systemic disease unknown to the patient or their general medical pra

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… Possibly the most likely cause of recurrent swelling of the lips is angioedema due to allergic disease. 4 There can be a wide array of precipitants, and the swelling may sometimes, but not always, be accompanied by swelling of the face (for example, around the eyes), tongue, pharynx and larynx. … C1 esterase inhibitor for ace-inhibitor angioedema: a case series and literature review. J Emerg Med 2020; 58: 121-127. 6. Jajam M, Bozzolo P, Niklander S. Oral manifestations of gastrointestinal disorders. J Clin Exp Dent 2017; 9: 1242-1248. 7. Suresh L, Radfar L. …