The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the ...true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests.
Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018.
We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery.
After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.
Hereditary angioedema is a life-threatening illness caused by mutations in the gene encoding C1 inhibitor (also called C1 esterase inhibitor) that lead to overactivation of the kallikrein-bradykinin ...cascade. BCX7353 is a potent oral small-molecule inhibitor of plasma kallikrein with a pharmacokinetic and pharmacodynamic profile that may help prevent angioedema attacks.
In this international, three-part, dose-ranging, placebo-controlled trial, we evaluated four doses of BCX7353 (62.5 mg, 125 mg, 250 mg, and 350 mg once daily) for the prevention of angioedema attacks over a 28-day period. Patients with type I or II hereditary angioedema with a history of at least two angioedema attacks per month were randomly assigned to BCX7353 or placebo. The primary efficacy end point was the number of confirmed angioedema attacks. Key secondary end points included angioedema attacks according to anatomical location and quality of life.
A total of 77 patients underwent randomization, 75 received BCX7353 or placebo, and 72 completed the trial. The rate of confirmed angioedema attacks was significantly lower among patients who received BCX7353 at daily doses of 125 mg or more than among those who received placebo, with a 73.8% difference at 125 mg (P<0.001). Significant benefits with respect to quality-of-life scores were observed in the 125-mg and 250-mg dose groups (P<0.05). Gastrointestinal adverse events, predominantly of grade 1, were the most commonly reported adverse events, particularly in the two highest BCX7353 dose groups.
Once-daily oral administration of BCX7353 at a dose of 125 mg or more resulted in a significantly lower rate of attacks of hereditary angioedema than placebo. Mild gastrointestinal symptoms were the principal side effect. (Funded by BioCryst Pharmaceuticals; APeX-1 ClinicalTrials.gov number, NCT02870972 .).
Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a ...deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.
Pomegranate is a berry fruit that has attracted a lot of attention since, besides its appetizing taste, it confers important health benefits when consumed. Pomegranate derivatives such as seeds are ...also an excellent nutritional source of bioactive components and functional lipids. The present study aimed to evaluate the influence of microwave-assisted and ultrasound-assisted extractions, under different extraction parameters (temperature, extraction time, solvent to sample ratio) for the recovery of the highest amount of pomegranate seed oil. There were not significant differences between the obtained oil yields for microwave-assisted and ultrasound-assisted extractions (18.38 and 17.64%, respectively). For both methods, temperature and solvent to sample ratio exerted the main influence on pomegranate seed oil extraction yield, whereas extraction time only affected microwave-assisted extraction. Based on the obtained results and considering economic issues, the best treatment was using ultrasound-assisted extraction at 45 °C, 10 min and a solvent to sample ratio of 1:5 (g/mL), with an oil yield of 17.64%. Six fatty acids were identified by GC/MS, with punicic acid (> 75%) as the major residue in pomegranate seed oil. The extracted oil showed antioxidant values of 9.81 and 3.93 mg TE/g of seed, with 91.29 and 98.28% scavenging activity against DPPH and ABTS radicals, respectively. The oil also exhibited a 95.99% of lipid oxidation inhibition. Pomegranate seed is a potential source of health-promoting compounds, such as punicic acid, and natural antioxidants with a high radical scavenging activity.
There is little information on pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency (C1INH-HAE). The aim of this study was to describe the effect of pregnancy ...and deliveries on symptoms of C1INH-HAE and review the need for and safety of treatments available during the study period.
Retrospective review using a purpose-designed questionnaire of 61 C1INH-HAE patients from 5 hospitals specialized in the management of HAE in Spain. The outcomes measured were number of pregnancies, changes in symptoms during pregnancy and delivery, mode of delivery, type of anesthesia during delivery, treatments received, and tolerance of treatments.
We reviewed 125 full-term pregnancies (89 without a prior diagnosis of C1INH-HAE), 14 miscarriages, and 4 induced abortions. Patients reported an increased frequency of C1INH-HAE symptoms in 59.2% of pregnancies (74/125) and the presence of symptoms throughout pregnancy in 40% (50/125). Prophylactic C1INH-HAE therapy was used during 9 (7.2%) of the 125 pregnancies. Nine patients--in 11 pregnancies (8.8 %)--received treatment for acute attacks. Most deliveries (n=110, 88%) were vaginal. A cesarean section was necessary in 15 cases (12%). Short-term prophylaxis with pdhC1INH was administered before 14 deliveries (11.2 %); 111 deliveries (88.8 %) were performed without premedication and were well tolerated. Anesthesia was used in 51 deliveries (40.8%).
Pregnancy has a variable influence on the clinical expression of C1INH-HAE. Attacks tend to occur more frequently but not to increase in severity. Vaginal delivery was mostly well tolerated. pdhC1INH prophylaxis should be administered prior to cesarean delivery and is also recommended before vaginal delivery if there are additional risk factors. pdhC1INH should always be available in the delivery room.
There are no Spanish guidelines or consensus statement on bradykinin-induced angioedema.
To review the pathophysiology, genetics, and clinical symptoms of the different types of bradykinin-induced ...angioedema and to draft a consensus statement in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals.
The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema (SGBA), a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings of the SGBA were held in Madrid to reach the consensus.
The pathophysiology, genetics, and clinical symptoms of the different types of angioedema are reviewed. Diagnostic approaches are discussed and the consensus reached is described.
A review of bradykinin-induced angioedema and a consensus on diagnosis are presented.
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