Eco-friendly solvent-based liquid-liquid extraction of phenolic acids from winery wastewater streams.

This study proposes liquid-liquid extraction (LLE) for the recovery of phenolic acids from winery wastewater replacing common volatile organic compounds (VOCs) with environmentally friendly solvents. On one hand, terpenes (α-pinene and p-cymene) and terpenoids (eucalyptol and linalool) were selected as green solvents and compared to common VOCs (ethyl acetate or 1-butanol). On the other hand, gallic acid (GA), vanillic acid (VA), syringic acid (SA) and caffeic acid (CA) were selected as phenolic acids to be recovered. The extraction performance was evaluated under different operation conditions: solvent-to-feed ratio, initial concentration of phenolic acids and temperature. This work also evaluated the back-extraction whole process global recovery and solvent regeneration, by means of aqueous NaOH solution. Eucalyptol has shown the highest overall global extraction performance (21.07 % for GA, 93.21 % for VA, 78.79 % for SA, and 80.57 % for CA) and lower water solubility compared to the best performing VOC solvent (1-butanol). Therefore, eucalyptol can be a potential eco-friendly solvent to replace VOCs for sustainable phenolic acid recovery from winery wastewater. Finally, to ensure a clean water stream after the LLE, the traces of solvent were completely removed by electrooxidation with boron-doped diamond anode at a current density of 422.54 A/m2.

The Immediate and Delayed Maximal Nonirritating Skin Testing Concentrations of ß-Lactam Antibiotics.

BACKGROUND: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin among guidelines. However, there is variability among guidelines for maximal ST NICs of cephalosporins. OBJECTIVE: To determine maximal immediate and delayed ST NICs of 15 ß-lactams in ß-lactam-tolerant and ß-lactam-naïve participants. METHODS: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 6 increasing concentrations of 1 or more ß-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm compared with negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted. RESULTS: A total of 747 participants with a median age of 64 (interquartile range: 54-72) years (52% male, 85% White, and 92% non-Hispanic) underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/mL): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely nonirritant close to or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data. CONCLUSIONS: Our results suggest that SPTs with undiluted stock ß-lactam antibiotic concentrations are nonirritant. Compared with previously published nonirritant concentrations, we propose a 2- to 50-fold increase to the maximal IDT and dIDT NICs of 15 ß-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.

Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis.

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.

A US-Based Multicenter Retrospective Report of Perioperative Anaphylaxis, 2010-2021.

BACKGROUND: US-based perioperative anaphylaxis (POA) studies are limited to single-center experiences. A recent report found that a serum acute tryptase (sAT) >9.8 ng/mL or mast cell activation (MCA) can predict POA causal agent identification. Urinary mast cell mediator metabolites (uMC) have not been studied in POA. OBJECTIVE: To analyze the epidemiologic data of POA, to determine if sAT or MCA can predict suspected causal agent identification, and to evaluate uMC utility in POA. METHODS: This study is a retrospective multicenter review of POA cases that were subcategorized by suspected causal agent identification status. sAT, MCA (defined as sAT >2 + 1.2 × serum baseline tryptase), and uMC (N-methylhistamine [N-MH], 11ß-prostaglandin-F2α [11ß-PGF2α], leukotriene E4 [LTE4]) were recorded. RESULTS: Of 100 patients (mean age 52 [standard deviation 17] years, 94% adult, 50% female, 90% White, and 2% Hispanic) with POA, 73% had an sAT available, 41% had MCA, 16% had uMC available, and 50% had an identifiable suspected cause. POA cases with an identifiable suspected cause had a positive MCA status (100% vs 78%; P = .01) compared with POA with an unidentifiable cause. An elevated median sAT did not predict causal agent identification. Positive uMC were not associated with suspected causal agent identification during POA. Patients with positive uMC had a higher median sAT (30 vs 6.45 ng/mL; P = .001) and MCA status (96% vs 12%; P = .001) compared with negative uMC patients. Patients with POA had an elevated acute/baseline uMC ratios: 11ß-PGF2α ratio > 1.6, N-MH ratio >1.7, and LTE4 ratio >1.8. CONCLUSIONS: The presence of MCA in POA is associated with suspected causal agent identification. Positive uMC possibly correlate with a higher sAT level and MCA status but require further study. The authors suggest applying an acute/baseline uMC ratio (11ß-PGF2α ratio >1.6, N-MH ratio >1.7, and LTE4 ratio >1.87) in patients with POA for MCA when a tryptase level is inconclusive during POA evaluations.

Predicting Penicillin Allergy: A United States Multicenter Retrospective Study.

BACKGROUND: Using the reaction history in logistic regression and machine learning (ML) models to predict penicillin allergy has been reported based on non-US data. OBJECTIVE: We developed ML positive penicillin allergy testing prediction models from multisite US data. METHODS: Retrospective data from 4 US-based hospitals were grouped into 4 datasets: enriched training (1:3 case-control matched cohort), enriched testing, nonenriched internal testing, and nonenriched external testing. ML algorithms were used for model development. We determined area under the curve (AUC) and applied the Shapley Additive exPlanations (SHAP) framework to interpret risk drivers. RESULTS: Of 4777 patients (mean age 60 [standard deviation: 17] years; 68% women, 91% White, and 86% non-Hispanic) evaluated for penicillin allergy labels, 513 (11%) had positive penicillin allergy testing. Model input variables were frequently missing: immediate or delayed onset (71%), signs or symptoms (13%), and treatment (31%). The gradient-boosted model was the strongest model with an AUC of 0.67 (95% confidence interval [CI]: 0.57-0.77), which improved to 0.87 (95% CI: 0.73-1) when only cases with complete data were used. Top SHAP drivers for positive testing were reactions within the last year and reactions requiring medical attention; female sex and reaction of hives/urticaria were also positive drivers. CONCLUSIONS: An ML prediction model for positive penicillin allergy skin testing using US-based retrospective data did not achieve performance strong enough for acceptance and adoption. The optimal ML prediction model for positive penicillin allergy testing was driven by time since reaction, seek medical attention, female sex, and hives/urticaria.

Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial.

Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33-61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness.

Effect of MetioNac® in patients with metabolic syndrome who are at risk of metabolic dysfunction associated fatty liver disease: a randomized controlled trial.

Introduction: Introduction: metabolic syndrome comprises a combination of diabetes, high blood pressure, and obesity, and metabolic associated fatty liver disease (MAFLD) is associated with it. Objective: to evaluate the effect of supplementation with S-adenosyl-L-methionine + N-acetylcysteine + thioctic acid + vitamin B6 (MetioNac®) for 3 months on lipidic and biochemical parameters in subjects with metabolic syndrome and at risk of MAFLD. The reduction in body weight and the oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) were also evaluated. Methods: patients with metabolic syndrome, at risk of MAFLD (FIB-4 < 1.30), and with an indication for weight reduction were recruited (n = 15). Control group followed a semipersonalized Mediterranean diet (MD) for weight reduction, according to the recommendations of the Spanish Society for the Study of Obesity (SEEDO). Experimental group, in addition to the MD, took three capsules of MetioNac® supplement per day. Results: compared with the control group, subjects taking MetioNac® showed significant (p < 0.05) reductions in the levels of TG and VLDL-c, as well as in total cholesterol, LDL-c, and glucose levels. They also showed increased levels of HDL-c. Levels of AST and ALT decreased after the intervention with MetioNac®, but this decrease did not reach statistical significance. Weight loss was observed in both groups. Conclusion: supplementation with MetioNac® may be protective against hyperlipidemia, insulin resistance, and overweight among metabolic syndrome patients. Further studies on this issue are needed in a larger population.

Introducción: Introducción: el síndrome metabólico se define como una combinación de diabetes, hipertensión arterial y obesidad, que se asocia con la enfermedad del hígado graso asociada a disfunción metabólica. Objetivo: evaluar el efecto de la suplementación con S-adenosil-L-metionina + N-acetilcisteína + ácido tióctico + vitamina B6 (MetioNac®) durante 3 meses sobre parámetros lipídicos y bioquímicos en sujetos con síndrome metabólico y en riesgo de enfermedad del hígado graso asociada a disfunción metabólica. También se evaluaron la reducción del peso corporal y los marcadores de estrés oxidativo malondialdehído (MDA) y superóxido dismutasa (SOD). Métodos: se reclutaron pacientes con síndrome metabólico, riesgo de enfermedad del hígado graso asociada a disfunción metabólica (FIB-4 < 1,30) y con indicación de reducción de peso (n = 15). El grupo control siguió una dieta mediterránea (DM) semipersonalizada para la reducción de peso, de acuerdo con las recomendaciones de la Sociedad Española para el Estudio de la Obesidad (SEEDO). El grupo intervención, además de la DM, tomó tres cápsulas diarias de MetioNac®. Resultados: en comparación con el grupo de control, los sujetos que tomaron MetioNac® mostraron reducciones significativas (p < 0.05) en los niveles de TG y VLDL-c, así como en los niveles de colesterol total, LDL-c y glucosa. También mostraron niveles elevados de HDL-c. Los niveles de AST y ALT disminuyeron después de la intervención con MetioNac®, pero esta disminución no fue estadísticamente significativa. También se observó una pérdida de peso en ambos grupos. Conclusión: la suplementación con MetioNac® puede proteger contra la hiperlipidemia, la insulinorresistencia y el sobrepeso en pacientes con síndrome metabólico. Sin embargo, es necesario realizar más estudios y seleccionar un mayor número de participantes.

Cumulative effect of AOC1 gene variants on symptoms and pathological conditions in adult women with fibromyalgia: a pilot study.

Introduction: The amine oxidase copper-containing 1 (AOC1) gene encodes for the diamine oxidase (DAO) enzyme. DAO is an enzyme that catabolizes some molecules, including histamine, and is the degradative enzyme in the polyamine catabolic pathway that is active in intestinal mucosal cells. Variants of AOC1 are associated with reduced DAO activity, resulting in accumulation of high levels of histamine and causing a wide range of neurological, gastrointestinal, and epidermal disorders, which are present in people with fibromyalgia. This study aimed to evaluate the impact of four AOC1 gene variants, namely, rs10156191, rs1049742, rs1049793, and rs2052129, on fibromyalgia symptoms measured by the Fibromyalgia Impact Questionnaire (FIQ), such as sleep disorders, atopic dermatitis, migraine, gastrointestinal (GI) disorders, allergies, and intolerances, in adult women with fibromyalgia. Methods: The sample consisted of 100 unrelated women with fibromyalgia between 33 and 60 years of age (48.48 years ±7.35), whose were diagnosed by a rheumatologist based on symptoms such as pain, stiffness, and fatigue. Single-nucleotide polymorphisms (SNPs) of AOC1 were identified using oral mucosa samples collected following a standard hygiene protocol. DNA was extracted, and gene variants of interest were analyzed using multiplex single-nucleotide primer extension (SNPE). Clinical data were collected using the FIQ and a series of variables that quantified the intensity and frequency of the symptoms. Results: The minor allele frequencies of rs10156191, rs1049742, rs1049793, and rs2052129 were 31.5, 10, 32.5, and 27%, respectively. Each variant was found to be in Hardy-Weinberg equilibrium, but partial linkage disequilibrium between AOC1 SNPs is suspected. The results show that fibromyalgia symptoms measured using the FIQ tend to increase with the number of risk alleles and that the intensity of dry skin and low stool consistency may be associated with an increase in the number of these alleles. Conclusion: This study constitutes the first step in investigating associations between fibromyalgia symptoms and candidate variants of the AOC1 gene in DAO enzyme activity. Identification of reduced DAO activity may improve the quality of life and treatment of symptoms in fibromyalgia patients.

Prevalence of Genetic Diamine Oxidase (DAO) Deficiency in Female Patients with Fibromyalgia in Spain.

Diamine oxidase (DAO) is an enzyme that metabolizes intestinal histamine. Single nucleotide polymorphisms (SNPs) of the Amine Oxidase Copper Containing 1 (AOC1) gene can lead to low enzymatic activity or functionality in histamine metabolism. This study aimed to determine the prevalence of DAO deficiency for four variants of the AOC1 gene, p.Thr16Met (rs10156191), p.Ser332Phe (rs1049742), p.His664Asp (rs1049793), and c.691G > T (rs2052129), in 98 Spanish women with fibromyalgia between the ages of 33 and 60 years, and compare the distribution of allelic and genotypic frequencies with those of European population samples in Hardy-Weinberg equilibrium extracted from the Allele Frequency Aggregator (ALFA) database. The patients' DNA was extracted, and analyzed using SNPE Multiplex (Single Nucleotide Primer Extension). The prevalence of genetic DAO deficiency was 74.5% based on the four variants of the AOC1 gene. SNP deficits were found at frequencies of 53.1% for p.Thr16Met, 49% for c.691G > T, 48% for p.His664Asp, and 19.4% for p.Ser332Phe. The allele and genotypic frequencies of the women with fibromyalgia did not differ from the European population. Variants of the AOC1 gene that are associated with genetic DAO deficiency could serve as a disruptive biomarker in patients with fibromyalgia. This study was registered in ClinicalTrials.gov Identifier: NCT05389761.

The Nonirritating Concentrations of Neuromuscular Blocking Agents and Related Compounds.

BACKGROUND: Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely among reports. OBJECTIVE: To determine maximal ST nonirritant concentrations (NICs) of NMBAs (cisatracurium, rocuronium, succinylcholine, and vecuronium), NMBA-reversal agents (neostigmine and sugammadex), and S-R-Cx in NMBA-tolerant and NMBA-naïve participants. METHODS: A single-center, prospective study between October 2019 and November 2021 of adult participants with or without a planned surgical procedure. The reference standard was tolerance of medication tested during a procedure (NMBA-tolerant group) before ST. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 5-7 increasing concentrations of 1 or more medications. All medications were reconstituted according to package insert instructions and diluted with 0.9% saline. A concentration was considered irritant when more than 5% of participants had a positive test per ST positivity criteria (wheal ≥3 mm than initial wheal and associated erythema of the same size or greater than wheal). We also compared our results with current guidelines. RESULTS: A total of 187 participants (78% NMBA-tolerant) underwent 7812 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT NICs (mg/mL): cisatracurium (0.02), rocuronium (0.05), succinylcholine (0.8), vecuronium (0.01), neostigmine (0.2), sugammadex (50), and S-R-Cx (sugammadex 7.14 + rocuronium 2). CONCLUSION: Our results suggest that SPT may be performed with undiluted stock concentrations. We confirm maximal IDT NICs for cisatracurium and rocuronium. We also propose that currently recommended maximal IDT NICs of succinylcholine, neostigmine, sugammadex, and S-R-Cx could be increased, whereas the maximal IDT NIC of vecuronium could be decreased compared with current guidelines and prior reports.

Existing differences between available lists of FODMAP-containing foods.

BACKGROUND AND AIM: reduced intake of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is useful to treat functional gastrointestinal disorders. However, there is no consensus on which foods should be included in the FODMAP list as FODMAP profile characterization is lacking for many different foods. This study aimed to emphasize the need for a unified FODMAP list to prevent patient confusion. We hypothesized that FODMAP lists do not include all products that may contain high levels of FODMAPs. METHODS: PubMed, ScienceDirect, Scielo, and Cochrane were searched to identify food composition tables, reviews, food analysis publications, laboratory analyses, and clinical trials containing FODMAP lists. RESULTS: of 1,308 articles identified, 10 were selected; 22.6 % of the 204 foods listed were classified differently among studies. This included almonds, avocados, banana, broccoli, soft cheese, eggplant, and walnuts. Nutritional guidance may be taken from existing FODMAP-related literature, but the information given is not always consistent. CONCLUSION: Unvarying lists of low FODMAP foods should be compiled to provide patients with accurate information on FODMAP dieting.

Knowledge and attitudes towards baby-led-weaning by health professionals and parents: A cross-sectional study.

OBJECTIVE: Baby-led-weaning (BLW) is a novel model of complementary feeding. Although there is little scientific evidence to support the suitability or superiority of this complementary feeding model, BLW is followed by many families today. The aim was to evaluate the knowledge and attitudes of a group of parents and health professionals regarding BLW in Spain. METHODS: This research was designed as a cross-sectional study in a sample of 502 parents and 364 health professionals. Two questionnaires generated and disseminated through Google forms were used. The differences between groups of professionals were analyzed using the Chi-Square test. RESULTS: 92.3% of professionals and 93.4% of parents knew about BLW. They recommend BLW "always" in 39.8% and 69.3% of the cases, and "sometimes" in 49.7% and 24.9%, respectively. Of the health professionals, 80.5% recommended starting complementary feeding as of six months, 36% of them using BLW, 24% followed traditional weaning, 3.3% bottle feeding and the remaining 36% did not indicate. Eighty-three percent recommended chewing as soon as the child showed interest. CONCLUSION: Both health professionals and parents recommend BLW and consider it helps promote the developmental milestones of the baby. Providing nurses with an adequate number of resources to guide parents on complementary feeding will continue to improve childcare.

Bosutinib-Induced Stevens-Johnson Syndrome and Evidence of Tolerance to a Structurally Dissimilar Tyrosine Kinase Inhibitor.

Bosutinib is a breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitor (TKI) used for the treatment of chronic myeloid leukemia (CML). Patients on TKIs may develop severe cutaneous adverse reactions (SCARs). A 73-year-old female with CML treated with a second-generation TKI (bosutinib) was evaluated after developing fever and a maculopapular exanthema with skin-peeling affecting her lips, oral mucosa, and genitals 10 days after starting the medication. She required hospitalization, bosutinib discontinuation, and management with intravenous corticosteroids and antibiotics. Patch testing was contraindicated due to the severity of the reaction. The patient was subsequently challenged with first-generation TKI along with careful observation without any adverse reactions. She has not reported any adverse reactions while on therapy in the last two years. In patients who have suffered from SCARs, the suspected triggers must be avoided in all instances. In some cases, the underlying condition limits the use of alternative agents, but low-concentration patch testing may help guide alternative therapies within the same medication group. There appears to be a low cross-reactivity among generational TKIs, and our patient benefited from treatment with a structurally dissimilar alternative TKI for her CML.

State-of-the-art beta-adrenoreceptor agonists for the treatment of asthma.

INTRODUCTION: Asthma, a heterogeneous disease, is characterized by chronic airway inflammation and hyperreactivity. ß2-adrenoreceptor agonists (ß2-agonists) remain pivotal for asthma management. Short-acting ß2-agonists (SABAs) result in rapid symptomatic alleviation and bronchospasm prevention. Patients experience significant clinical benefits from therapy with long-acting ß2-agonists (LABAs) with efficacy to bronchodilate, and prolonged lung function betterment. Recently discovered ß2-agonists with longer half-lives offer once-daily dosing. AREAS COVERED: The authors provide a thorough review of the pharmacokinetics, pharmacodynamics, efficacy, tolerability, classification, and safety of ß2-agonists through an in-depth review of current literature using these databases: U.S. National Institutes of Health's National Library of Medicine (NIH/NLM), PubMed Central, and NLM clinical trials. EXPERT OPINION: ß2- agonists act primarily on airway smooth muscle cells and are quintessential for adequate asthma management. Given their pharmacodynamic and pharmacokinetic properties, SABAs are used as rescue medication. Notably, the current Global Initiative for Asthma (GINA) strategy document recommends using LABA/inhaled corticosteroid combinations both as a daily controller and as a rescue medication. Clinicians should assess this new treatment plan on a per-case basis, making sure to evaluate inhaler adherence and treat modifiable risk factors. The development of next-generation ß2- agonists is an exciting research area that could significantly improve patients' adherence to treatment regimens and, consequently, asthma control and quality of life.

IgE-Mediated Reaction to Levamisole: Evaluation of a Patient With Severe Anaphylaxis.

Levamisole has been used as adjuvant immunomodulatory therapy for certain conditions such as amyotrophic lateral sclerosis (ALS). We present a case of a 70-year-old man with ALS who was started on levamisole with adequate response. Within 10 days of treatment, he developed a maculopapular non-pruritic rash on his extremities, and the medication was discontinued. However, two days later, he developed angioedema of the face and hands, urticaria in the extremities and torso, and throat closing sensation that was successfully treated in the emergency department with epinephrine, systemic corticosteroids, and antihistamines. Eight hours later, he presented with recurrent facial angioedema. He was transferred to the ICU and received two more doses of epinephrine and intravenous methylprednisolone. The patient fully recovered within 72 hours and was discharged with the indication to avoid levamisole. One month after the reaction, skin tests (prick and intradermal) with 10-fold dilutions of 550 mg/mL levamisole were positive at a concentration of 55 mg/mL (1:10 dilution). Since the patient developed anaphylaxis and tested positive for levamisole on intradermal testing, and after discussing the options with him, we decided to advise against using this medication since the benefits did not outweigh the risks of administration. This case highlights that IgE-mediated reactions to levamisole, while rare, can occur and be life-threatening. Shared decision-making should be done between patients and physicians after open, evidence-based discussions.

Perioperative Resumption of Direct Oral Anticoagulants: Review of the Mayo Clinic Experience.

OBJECTIVE: We aimed to review recommendations for the postoperative resumption of direct oral anticoagulants (DOACs) and report complications 30 days postoperatively. METHODS: We retrospectively reviewed patients receiving DOAC therapy who underwent preoperative evaluations from January 1, 2015 through May 30, 2018. We noted days that DOAC therapy was withheld, postoperative time until resumption of the DOAC, and complications within 30 postoperative days. RESULTS: A total of 317 patients were included. Ten had complications. Complication rates among patients stratified by time to resumption were not significantly different, except for the deep vein thrombosis rate when DOACs were resumed after 72 hours (n = 2 [4.17%]; P = 0.02). The total time without DOACs did not affect the complication rates. CONCLUSIONS: We suggest withholding DOACs for 48 to 72 hours before surgery and resuming them 48 to 72 hours after surgery, if safe. The interruption of therapy was not associated with an increase in thrombotic events for patients who resumed DOACs within 72 hours postoperatively. Patients who resumed DOACs after 72 hours postoperatively had a low rate of thrombotic complications.