Nonimmunologic Reactions Research Articles

Navigating Food Allergies: Advances in Diagnosis and Treatment Strategies.

Food allergy is a major health concern worldwide, encompassing both immunologic and non-immunologic reactions. This review thoroughly examines the pathophysiology, clinical manifestations, and treatment options for various types of food allergies. Immunologic food allergies, including IgE-mediated reactions such as oral allergy syndrome and systemic anaphylaxis, pose various diagnostic and management challenges. Non-IgE-mediated reactions such as food protein-induced enterocolitis syndrome, dermatitis herpetiformis, and proctocolitis necessitate individualized patient care.In addition, mixed reactions such as eosinophilic esophagitis and atopic dermatitis complicate the clinical picture. Skin prick tests, serum-specific IgE tests, and oral food challenges are all necessary for accurate food allergy diagnosis. The primary therapeutic options are allergen avoidance, epinephrine-based emergency management, and emerging treatments like immunotherapy. Our review emphasizes the importance of multidisciplinary collaboration and ongoing research in improving our understanding and managing food allergies, promising a brighter future for those affected.

Shellfish allergy – diagnostic approach

Shellfish allergy is one of the most common food allergies, with an estimated prevalence of 3% in the general population. Crustaceans and mollusks are part of this food category, being capable of immunologic hypersensitivity reactions (IgE-mediated, as well as non-IgE-mediated), but also non-immunologic reactions, based on intoxication with certain neurotoxins from contaminated seafood, in which neurological but also gastrointestinal symptoms predominate. The clinical picture in IgE-mediated hypersensitivity reactions can vary in severity, from mild reactions such as oral allergy syndrome to severe reactions such as anaphylaxis. Among the delayed, non-IgE mediated reactions, we can identify food protein-induced enterocolitis syndrome, food protein-induced enteropathy and food protein-induced allergic proctocolitis, which mainly involve gastrointestinal symptoms. Over the past decades, the knowledge gained regarding the characteristics of different allergens has improved the diagnostic approach. Thus, for an accurate diagnosis of seafood-induced allergy, a thorough history, along with skin prick testing and specific IgE dosing are essential, and when these are insufficient, an oral challenge test can disentangle causality.

IgE-Mediated Shellfish Allergy in Children.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed.

Post transfusion reactions in animals (review)

Currently, veterinary specialists are increasingly using blood transfusion in various pathological conditions of the animal body. But at the same time, the effect of hemoconservatives on the body of animals and whole blood has been little studied. The review article provides an analysis of the results of studies of post-transfusion complications in the period from 2008 to 2022. Particular attention in these studies was paid to the frequency of occurrence, the quality of blood or its component, the compatibility of the donor and recipient, complications during and after hemotransfusion. Post-transfusion reactions that can occur as a result of blood transfusion have shown a number of possible immunological and nonimmunological reactions of the organism of animals and humans, the origin of which has been little studied. Posttransfusion reactions of the body include incompatibility reactions, reactions to erythrocyte proteins, reactions to platelets and leukocytes during plasma transfusion, anaphylactoid reactions, hypothermia, heparinization, coagulopathy and thrombosis, microbial contamination, hyperammonemia, hypophosphatemia, hyperkalemia, acidosis, pre-transfusion hemolysis, hemosiderosis. The frequency of occurrence of these reactions has not been sufficiently studied, since mainly isolated cases or studies with a small sample are described. The problem of post-transfusion reactions in animals in our country began to be studied recently. Post-transfusion reactions are practically not monitored, since this requires additional research in a hospital veterinary clinic.

Do mast cells contribute to the continued survival of vertebrates?

This study is an attempt to shed light on why the connective tissue mast cell (MC) is preserved in all species with a blood circulatory system, i.e., the vertebrates since >500 million years, which suggests that the MC performs as yet not understood indispensible life‐promoting actions. The literature survey focuses on data in published papers on MC functions in immunological and nonimmunological reactions, host protection, pregnancy, inflammation, and wound healing. All data are thus accessible to the reader. The MC is a secretory cell with a unique mediator profile. A distinctive role for MCs is defined not only by their extensive mediator composition but also by their prominent ability to affect the vasculature to expedite selective cell recruitment and permeability changes and to set the stage for an appropriate acquired response. MCs, harboring a wide range of surface membrane receptors, are activated by the major female sex hormones as well as by diverse potentially adverse stimuli. MC activation/degranulation creates a presumably unique triad tissue response in physiological and pathological situations alike: extracellular matrix degradation and tissue remodeling, de novo cell proliferation, and de novo angiogenesis. As shown in the literature, MC‐activation is crucial for successful female reproduction in the mouse, implying one of possibly several yet unidentified physiological roles of MCs. Moreover, the activated MC aids newborns to survive to reproductive age owing to its key beneficial actions in inflammation and wound healing. Thus, a not previously described life‐perpetuating loop spanning generations are apparently formed, which, hypothetically, could contribute to the continued survival of the vertebrates.

Food intolerance

Food intolerance is a non-immunological response induced by a food or food component in a dose that is normally tolerated. It includes pseudo allergic and pharmacological effects caused by: salicylates, biogenic amines, sulphites, sodium glutamate, colours and preservatives, sweeteners, or enzymopathies. The pathophysiology, clinical manifestations, diagnosis and treatment of the most common food intolerances have been presented in this review article. The literature search was done with the help of the following keywords: intolerance, food, additives, carbohydrates and gluten within PubMed, Embase, Scopus, SCIndeks and Hrčak databases. According to the literature, it may be argued that the lack of standardized tests accounts for the discrepancy between the perceived prevalence of food-related adverse effects, which are extremely common, and the actual prevalence of non-immunological reactions to food within these events. Food intolerance is manifested primarily by gastrointestinal and then extraintestinal (neurological, cardiovascular, respiratory and dermatological) signs and symptoms. Diagnosis requires a detailed medical history, physical examination, as well as keeping a diet and symptom diary, implementing an elimination diet and double-blind placebo-controlled oral food exposure tests. Treatment includes dietary modification, supplementation and treatment of the underlying condition in persons with secondary intolerance.

Public health aspects of food allergy and food intolerance: Literature review

Aim of the paper was to make a review of available evidence for food allergies and food intolerance, to make a distinction between allergy and intolerance, and to emphasize the current knowledge about the prevalence and preventive measures. We made a search through PubMed and Google scholar, using the search terms "food", "allergy", "intolerance", "prevalence", "prevention" and "measures" for the period from 2000 to 2020, in order to find appropriate papers and publications. Food intolerance is defined as a non-immunological reaction to certain natural food ingredients or food additives that causes pharmacological, metabolic and gastro-intestinal reactions to food or food compounds. Food allergy is defined as an immune-mediated reaction to food, that is almost always mediated by immunoglobulin E (IgE). The worldwide prevalence of IgE-mediated allergic reactions is not exactly known. It is believed that about 1-2% of adults and between 5-7% of the children suffer from some type of food allergy and this number is growing. The most frequent specific food allergens are eggs, fish, peanuts, nuts, cow's milk, cereals containing gluten, (such as wheat, rye, barley, oats) seafood, soybeans, sesame, celery and mustard. Food intolerance can sometimes be controlled by limiting the amount of a certain type of food that is consumed, but when it comes to food allergies, much stricter avoidance of the food is required. Only food allergy, not food intolerance, can lead to a potentially fatal anaphylaxis reaction. In order to avoid food allergy, it is necessary to label the products for the presence of allergens.

Contact Dermatitis in Tertiary Hospital: A 2-year Retrospective Study

Background: Contact dermatitis (CD) is a skin inflammatory caused by allergen or irritant that generates public health impact. CD is classified into two types, based on its etiological perspective, namely allergic contact dermatitis (ACD) due to a hypersensitivity type IV reaction and irritant contact dermatitis (ICD), which is a non-immunological reaction. Purpose: To determine the profile of CD patients at Dermatology and Venereology Outpatients Unit of Dr. Soetomo General Academic Hospital Surabaya in January 2018 – December 2019. Methods: A retrospective study by observation and recording data. The results of the data recap were then processed using Microsoft Excel to obtain conclusions. Result: The results obtained were ACD (61.9%) and ICD (38.1%), aged 26-45 years (32.7%), female (79.3%). The most frequent occupation was housewives (25.3%), followed by private employees (24.5%). The most suspected causative substance was cosmetic (47.7%). The most common skin disease history was food allergy (11%), followed by drug allergy (2.8%), and atopic dermatitis (2.3%). The most frequent manifestation was acute (69.8%), with the most clinical presentation was erythematous macules (35%). Most therapies were given in combination (73.6%), with antihistamines (61%) and topical corticosteroids (49.2%) were the most prescription drug. Conclusion: ACD was more common than ICD, mostly in a female, dominated in the 26-45 years old. Housewife was the most occupational. Cosmetic was the most suspected causative substance. Food allergy was the most skin disease history. Acute was the most frequent manifestation. Erythematous macules were the most clinical presentation. Antihistamine and corticosteroid are the most common drug in combination therapy.

Multiple Drug Intolerance Syndrome in Fibromyalgia

Multiple drug intolerance syndrome (MDIS) describes patients with non-immunologic reactions to ≥3 drug classes. This can severely limit treatment options for affected patients. Rates of MDIS in fibromyalgia have not been previously described 1,479 patients with a diagnosis of fibromyalgia seen within our university health system in the last year were evaluated by retrospective chart review. Based on prior studies, patients with 10 or more listed allergies were considered to have MDIS. Chi-square testing and binary logistic regression were used for analysis. 128 (8.65%) patients with fibromyalgia met the definition of MDIS. The average number allergies listed for fibromyalgia patients was 3.7, while the average for age and sex matched controls was 1.4. On regression analysis, patients with fibromyalgia were found to be 6 times more likely to have MDIS (OR 6.29, CI 4.74-8.36). An active diagnosis of anxiety (X2 = 13.00, p < 0.0001) or depression (X2 = 7.14, p =0.008) was associated with MDIS. A Charlson Comorbidity Index score of ≥4 was associated with MDIS in patients with fibromyalgia (X2 = 41.44, p < 0.0001) and estimates a 10 year survival of 53%. Additionally, having >10 outpatient visits within the last year was associated with MDIS (X2 = 30.79, p < 0.0001 The association of MDIS with multiple comorbidities and frequent health care utilization in patients with fibromyalgia raises concerns that MDIS may limit therapies in these already complex patients. Additional studies are needed to explore this further.

Associations between HLA-A, -B, and -C alleles and iodinated contrast media-induced hypersensitivity in Koreans.

A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total, 126 patients who underwent contrast-enhanced computed tomography studies through outpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, were ICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 with immediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotyping was performed using a PCR sequence-based typing method. Four kinds of ICM were used: iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivity patients was iopromide. Significant difference in the frequency of HLA-B*58:01 (odds ratios [OR], 3.90; p = 0.0200, 95% confidence interval [CI], 1.16–13.07) was observed between ICM-induced immediate hypersensitivity and control. There were statistically significant differences in the frequencies of the HLA-B*38:02 (OR, 10.24; p = 0.0145; 95% CI, 1.09–96.14) and HLA-B*58:01 (OR, 3.98; p = 0.0348; 95% CI, 1.03–15.39) between iopromide-induced immediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivity remains unknown, but this study showed associations, although weak, with HLA-B*58:01 alleles for ICM-induced immediate hypersensitivity and HLA-B*38:02 and HLA-B*58:01 for iopromide-induced immediate hypersensitivity as risk predictors. Further studies are needed to validate the associations in larger samples and to identify the functional mechanism behind these results.

Classification of adverse food reactions.

Foods can induce adverse reactions by a variety of mechanisms. An understanding of the characteristic signs and symptoms and the related mechanisms of adverse food reactions allows the clinician to efficiently diagnose and treat patients. Adverse reactions to foods can be classified based on whether there is a nonimmunologic or immunologic basis for symptoms. Food intolerance, or a nonimmunologic reaction, includes a range of responses to foods that result primarily from an individual's intrinsic inability to metabolize a component of the food, e.g., lactose sugar in dairy products. Other nonimmunologic adverse reactions may be attributed to food toxins or pharmacologic properties pharmacologic properties of foods themselves. Immunologic adverse reactions, in contrast, involve immune responses to food and are termed food allergy. Food allergy may further be categorized based on the underlying immunopathophysiology as immunoglobulin E (IgE) mediated, non-IgE mediated, or cell mediated. Some chronic allergic responses involve a combination of immune mechanisms. This review provides a general classification system for adverse food reactions and describes specificconditions.

Adverse reactions of systemic drugs in the oral cavity

Adverse reactions of systemic drugs in the oral cavity

Food Allergies

Food allergy represents a rapidly growing public health problem in the United States and other westernized nations. Adverse reactions to foods are categorized as either immunologic or nonimmunologic reactions. This distinction is highly important but often confusing to patients and physicians unfamiliar with allergy, who may simply describe any adverse reaction to a food as an “allergy.” A food allergy is an immune-mediated, adverse reaction to one or more protein allergens in a particular food item involving recognition of that protein by specifically targeted IgE or allergen-specific T cells. This chapter discusses the definition, pathophysiology, epidemiology, testing, management, prognosis, and natural history of food allergy. Clinical manifestations are systematically covered, including cutaneous, respiratory, cardiovascular, and gastrointestinal reactions, as well as eosinophilic esophagitis, food protein–induced enterocolitis syndrome, and oral allergy syndrome. Emerging treatments such as food oral immunotherapy are also reviewed. Tables outline signs and symptoms of immediate hypersensitivity reactions to food, the prevalence of major food allergens in the United States, common patterns of cross-reactivity among foods, clinical criteria for the diagnosis of anaphylaxis, and clinical studies involving treatment for food allergies. Figures illustrate the classification of adverse reactions to food, esophageal histology, visual and radiographic features of eosinophilic esophagitis, and a food allergy action plan. This review contains 4 figures, 8 tables, and 64 references. KeyWords: Food allergy, Hypersensitivity, IgE-mediated allergy, Eosinophilic esophagitis, Anaphylaxis

Food Allergies

Food allergy represents a rapidly growing public health problem in the United States and other westernized nations. Adverse reactions to foods are categorized as either immunologic or nonimmunologic reactions. This distinction is highly important but often confusing to patients and physicians unfamiliar with allergy, who may simply describe any adverse reaction to a food as an “allergy.” A food allergy is an immune-mediated, adverse reaction to one or more protein allergens in a particular food item involving recognition of that protein by specifically targeted IgE or allergen-specific T cells. This chapter discusses the definition, pathophysiology, epidemiology, testing, management, prognosis, and natural history of food allergy. Clinical manifestations are systematically covered, including cutaneous, respiratory, cardiovascular, and gastrointestinal reactions, as well as eosinophilic esophagitis, food protein–induced enterocolitis syndrome, and oral allergy syndrome. Emerging treatments such as food oral immunotherapy are also reviewed. Tables outline signs and symptoms of immediate hypersensitivity reactions to food, the prevalence of major food allergens in the United States, common patterns of cross-reactivity among foods, clinical criteria for the diagnosis of anaphylaxis, and clinical studies involving treatment for food allergies. Figures illustrate the classification of adverse reactions to food, esophageal histology, visual and radiographic features of eosinophilic esophagitis, and a food allergy action plan. This review contains 4 figures, 8 tables, and 64 references. KeyWords: Food allergy, Hypersensitivity, IgE-mediated allergy, Eosinophilic esophagitis, Anaphylaxis

Food allergy and anaphylaxis.

Anaphylaxis is a severe and potentially life-threatening allergic reaction. There are numerous potential causes, with food allergy being the leading cause in children and the focus of this review. Most reactions involve an IgE-mediated mechanism, although non-IgE-mediated and nonimmunologic reactions can occur. Various cofactors to be discussed can place certain individuals at an increased risk of severe or fatal anaphylaxis. The clinical manifestations of anaphylaxis are broad and may involve multiple body systems. Diagnosis of food-related anaphylaxis is primarily based on signs and symptoms and supported, wherever possible, by identification and confirmation of a culprit food allergen. First-line treatment of anaphylaxis is intramuscular administration of epinephrine. Long-term management is generally focused on strict allergen avoidance and more recently on food desensitization using immunotherapy. This review provides an overview of anaphylaxis with a specific focus on food allergy.

ID:3003 Increase in CD34 cells in peripheral blood following HLA randomized, ABO-matched cord blood transfusion in patients with advanced malignancy and anemia: Prognostic implications

Cord blood is a safe alternative of adult blood for transfusion given its content of fetal and adult haemoglobin, platelet and WBC counts, and a plasma filled with inflammatory and non-inflammatory cytokines and growth factors. It also has a hypoantigenic nature and altered metabolic profile and is rich in haematopoietic stem cells (CD34) . It has potential for treatment of anemia in diseases of different aetiologies including malignancy. &#x0D; ​&#x0D; STUDY DESIGN:&#x0D; In the present study, 46 sex and HLA-randomized patients suffering from advanced malignancy and anemia (Hb 8 Gm percent or less) were treated with placental cord blood transfusion. CD34 cells were collected from peripheral blood 72 hours after transfusion and variations were analyzed for prognostic implication. The study period was between 16 August 1999 and 16 May 2006.&#x0D; ​&#x0D; RESULTS AND ANALYSIS:&#x0D; Among the forty-six cases included in this study , Case no 2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case no 46 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 14 received 15 units (metachronous lymph node metastatsis), Case 19 received 14 units (breast cancer), and Case 25 received seven units (lung cancer).&#x0D; ​&#x0D; There was no transfusion-related visible immunological or nonimmunological reaction in any patient. Studies of CD34 levels after 72 hours of transfusion showed an initial rise followed by a fall in twenty-two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and the rest of the cases demonstrated a sustained rise from the baseline, i.e, 56% to 99% of peripheral mononuclear cells and a sustained high CD34 level.&#x0D; ​&#x0D; CONCLUSION:&#x0D; This preliminary study indicates that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without provoking clinical graft vs host disease perhaps due to a possible background structural or functional immune suppression in advanced malignancy.&#x0D; From the cord blood transfusion impact we could clinically divide the enrolled advanced cancer patients to a relatively good (Group A) and bad prognostic(Group B) variety of cancer. The survival rate of patients where we detected a persistant rise of CD34 in peripheral blood after 3 units or more of transfusion of HLA randomized ABO matched and screened cord blood was over 3 years and the cases where there are no rise of peripheral blood CD34 level in spite of repeated transfusion of 5- 32 units of cord blood died within 3 months or earlier (p value less than .01)

Visible light-switched cytosol release of siRNA by amphiphilic fullerene derivative to enhance RNAi efficacy in vitro and in vivo.

We designed a novel photosensitive amphiphilic carrier (C60-Dex-NH2) for efficient and controllable siRNA delivery, which can be used in gene therapy. We showed that C60-Dex-NH2 could destroy lysosome membrane via controllable generation of ROS when exposed to light, which can help siRNA to escape from lysosome before degradation. This can enhance the gene silencing efficiency significantly and provides a useful way to regulate RNAi efficiency by light. One advantage for C60-Dex-NH2 system is C60 has broad absorbance spectrum and can be activated by weak visible light; Furthermore, C60-Dex-NH2 has a specific amphiphilic structure, which may prevent siRNA from degrading and allows C60-Dex-NH2 to embed into the lipid membrane of lysosome to improve the ROS induced lysosomal disturbance after internalization.

Natural evolution in patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity with NSAIDs-induced urticaria/angioedema (NIUA) the most common phenotype. Loss of hypersensitivity has been reported for IgE-mediated reactions; however, it has not been assessed in nonimmunological reactions such as NIUA. We evaluated NSAID-hypersensitivity over time in NIUA patients. Patients confirmed as NIUA by positive drug provocation test (DPT) with acetylsalicylic acid (ASA) during 2005-2012 (V1) were included (n=38). Subjects were prospectively re-evaluated by DPT with ASA/other NSAIDs at two time points between 2013 and 2015 (V2 and V3). Atopy was assessed by skin prick test (SPT) using inhalant and food allergens. Patients were evaluated at V1 and re-evaluated after 60 months (V2; IR:48-81) and a further 18 months (V3; IR:14-24). At V2, the majority (24; 63.15%) tolerated ASA and other NSAIDs (Group A) while 14 (36.84%) still reacted (Group B). At V3, all Group A patients remained tolerant; all Group B patients remained hypersensitive. The number of previous episodes reported at V1 and the percentage of reactions induced by ASA/ibuprofen were significantly lower in Group A (P=.005 and P=.006, respectively). Group A patients developed tolerance 72 months (IR:45-87) after their last evaluated reaction (V1); this interval was shorter in nonatopics (P=.003), patients who experienced reactions over 1 hour after NSAIDs administration (P=.001), and those who experienced isolated urticaria after NSAID intake (P=.024). NIUA patients may develop tolerance to NSAIDs over time, a process that seems to be influenced by atopy and type of clinical reaction.

Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial

BackgroundLiver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far.The aim of this study is to compare three transfusion strategies (routine coagulation test-guided – ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis.Methods/designDesign and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. Inclusion criteria: adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis.DiscussionThis study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly reduce transfusion of blood products in this population, leading to a reduction in costs and transfusion-related adverse reactions. In this manner, this trial will add evidence in favor of reducing empirical transfusion in severely ill patients with coagulopathy.Trial registrationClinicalTrials.gov, identifier: NCT02311985. Retrospectively registered on 3 December 2014.

Drug-Induced Anaphylaxis: Clinical Scope, Management, and Prevention

Drug-induced anaphylaxis (DIA) is a severe, life-threatening reaction occurring after drug exposure. It is an important cause of anaphylaxis and accounts for up to one third of drug hypersensitivity reactions. As in other anaphylaxis reactions, immunoglobulin E (IgE) has an important role in its mechanism, but other non-immunological reactions may also occur in DIA. Cutaneous and respiratory symptoms are present in a majority of patients, and cardiovascular events are more common in elderly patients. A complete work up is recommended not just to offer safe alternatives, but also to avoid incorrect labeling of patients as allergic to drugs. The investigation includes in vitro tests when available, followed by skin prick and intradermal tests. Although provocation tests are still considered the “gold standard” for the diagnosis of drug allergy, in DIA, the risk versus benefit ratio must be analyzed. Non-steroid anti-inflammatory drugs and antibiotics are the drug classes more frequently involved. Neuromuscular blocking agents, chemotherapeutic drugs, and biologics are commonly related to reactions in a hospital setting. Prevention measures include an individualized education plan, with recommendations to avoid the culprit drug and potential cross-reactive medications. In selected patients, desensitization can induce a temporary state of tolerance. Protocols are available and can be adapted for drugs used in different situations, from cancer treatment to enzyme replacement therapy.