Atopy and Response to Omalizumab Treatment in Chronic Spontaneous Urticaria.

INTRODUCTION: The possible influence of sensitization to aeroallergens on omalizumab response in chronic spontaneous urticaria (CSU) has been insufficiently investigated. This study's aim was to investigate atopy's influence on omalizumab response in CSU patients. METHOD: Retrospective study of CSU patients followed at a Portuguese Urticaria Center of Reference and Excellence (UCARE), treated with omalizumab for at least 6 months, between 2015 and 2022. At T0, all patients underwent quantification of specific immunoglobulin E (IgE) for total extract of most prevalent aeroallergens (ImmunoCAP Thermo Fisher Scientific®) and were divided in 2 groups, according to their response to omalizumab during the first 16 weeks of treatment: responders (R) (UAS7 <7) versus partial (PR) (UAS7 = 7-15) and nonresponders (UAS7 >15). R were further classified as fast (FR) (4-6 weeks) and slow responders (SR) (12-16 weeks). Total serum IgE, circulating eosinophil, and basophil counts were compared between groups at T0. p < 0.05 was considered statistically significant (SPSS® v25.0). RESULTS: Ninety-six patients (80% female) were studied, mean age 49 ± 14 years. Median CSU duration pre-omalizumab was 3 (0.6-20) years and mean omalizumab treatment duration was 3.7 ± 2.3 years. 38 (40%) had concomitant chronic inducible urticaria and 72 (75%) angioedema. Based on positive results of the specific IgE assay, 35 patients (36%) were considered atopic. Most patients (n = 30; 86%) were sensitized to house dust mites (HDM) (Dermatophagoides farinae = 28, Dermatophagoides pteronyssinus = 27, Blomia tropicalis = 19, Lepidoglyphus destructor = 17), followed by pollens (n = 12; 34%) (mixture of grasses = 10, Olea europaea = 7, Parietaria officinalis = 6), epithelia (n = 9; 26%) (dog = 8, cat = 7), and fungi (Alternaria alternata = 4; 11%). Eight patients (23%) were monosensitized to HDM and 4 (11%) to pollens. No significant association was found between aeroallergen sensitization and CSU duration, concomitant chronic inducible urticaria, or angioedema. Atopic patients featured significantly higher levels of baseline total serum IgE than nonatopic (469 vs. 94 U/mL, respectively; p = 0.0009). Mean baseline counts of eosinophils and basophils were not significantly different between atopic and non-atopic, respectively: eosinophils (128 vs. 121/mm3) and basophils (26 vs. 28/mm3). Regarding response to omalizumab, most patients (58; 60%) were responders: FR - 46 (79%); SR - 12 (21%). There was no significant association between aeroallergen sensitization and omalizumab response or speed of response. CONCLUSIONS: As far as we know, this is the first study exploring the influence of atopy sensitization pattern on omalizumab response in CSU. According to our results, presence of atopy/sensitization pattern does not influence omalizumab response in CSU patients.

Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria.

BACKGROUND: According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab. OBJECTIVES: The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction. METHODS: Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed. STATISTICAL ANALYSIS: SPSS® (v25.0), p < 0.05 statistically significant. RESULTS: Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders. CONCLUSIONS: A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

BACKGROUND: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. METHODS: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. RESULTS: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. CONCLUSION: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.

Clinical pharmaceutical screening in critical situations in a radioiodine therapy management service.

Radioiodine therapy can be used in differentiated thyroid carcinoma and requires extensive evaluation to ensure effectiveness and safety. Therefore, it is necessary to evaluate all health problems and medications used in the pre-radioiodine therapy period and comprehensive medication managementservices can serve as a screening tool in this context. The present study aims to describe critical clinical situations identified during the initial assessments of a comprehensive medication management service offered to differentiated thyroid carcinoma patients pre-radioiodine therapy, and the pharmaceutical interventions performed to solve them. A descriptive study with regard to the initial ten months of a comprehensive medication management service was carried out in a large oncology hospital (Rio de Janeiro, Brazil). Descriptive analysis was used to describe the critical clinical situations identified, as well as the correspondent drug therapy problems and the type, acceptability, and outcomes of the pharmaceutical interventions performed to solve them. Thirty patients with an average of 45.8 years and 5.1 medications were evaluated. Five critical clinical situations were identified; corresponding to drug therapy problems two(needs additional drug therapy - n = 4) and drug therapy problems four (dosage too low - n = 1). All pharmaceutical interventions were accepted. The comprehensive medication management service provision pre-radioiodine therapy is feasible and represents an important screening strategy.

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Antihistamine-resistant chronic spontaneous urticaria remains undertreated: 2-year data from the AWARE study.

BACKGROUND: Real-world evidence describing the benefits of recommended therapies and their impact on the quality of life (QoL) of chronic urticaria (CU) patients is limited. OBJECTIVE: To investigate disease burden, current treatment schedule, and the use of clinical resources by patients with H1 -antihistamine-refractory CU in Europe. METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global, prospective, non-interventional study in the real-world setting, sponsored by the manufacturer of omalizumab. Disease characteristics, pharmacological treatments, and health-related QoL of patients (N = 2727) ≥18 years of age diagnosed with H1 -antihistamine-refractory chronic spontaneous urticaria (without inducible urticaria) for >2 months are reported here. RESULTS: Of the 2727 patients included, 1232 (45.2%) and 1278 (46.9%) were successfully followed up for any assessment and for the key outcome, the urticaria control test (UCT) score, respectively, and patients with complete remission (14.1%) were excluded from analyses.The proportion of patients with uncontrolled CSU (UCT score <12) dropped from 78% (n/N = 1641/2104) at baseline to 28.7% (n/N = 269/936) after two years of participation in the AWARE study. In addition, the proportion of patients with no impact of CSU on their QoL (assessed by the Dermatological Life Quality Index) increased to 57% (n/N = 664/1164) from 18.7% (n/N = 491/2621) at baseline. Emergency room visits (2.4% [n/N = 7/296] vs 33.5% [n/N = 779/2322]) and hospital stays (1.7% [n/N = 5/296] vs 24.2% [n/N = 561/2322]) reduced at Month 24 vs baseline. Overall, 23.2% (n/N = 26/112) patients on non-sedating H1 -antihistamines (nsAH) and 41.9% (n/N = 44/105) patients on up-dosed nsAH had uncontrolled CSU (UCT <12) at Month 24. In omalizumab-treated patients, 27.1% (n/N = 78/288) had uncontrolled CSU at Month 24. CONCLUSION: These data confirm improvements for most patients with CSU over a 2-year follow-up period. Further studies are needed to understand the differences between guideline recommendations and reported management.

Food allergy-From food avoidance to active treatment.

The prevalence of food allergy (FA) has increased too rapidly, possibly due to environmental factors. The guidelines recommend strict allergen avoidance, but FA is still the main cause of anaphylaxis in all age groups. Immunotherapy is the only treatment able to change the course of allergic disease, and oral immunotherapy (OIT) is the more effective route in FA. However, it carries the risk of adverse reactions, including anaphylaxis. To improve OIT safety, adjuvant therapy with the immunoglobulin E (IgE) monoclonal antibody omalizumab has been extensively used. Results suggest particular benefit in patients with high risk of fatal anaphylaxis. An alternative approach is to use omalizumab instead of OIT to prevent severe allergic reactions upon accidental exposure. This paper reviews current evidence regarding IgE-mediated FA, focusing on natural tolerance and food sensitization acquisition, and on avoidance measures and their limitations.

Complexity of Cardiotocographic Signals as A Predictor of Labor.

Prediction of labor is of extreme importance in obstetric care to allow for preventive measures, assuring that both baby and mother have the best possible care. In this work, the authors studied how important nonlinear parameters (entropy and compression) can be as labor predictors. Linear features retrieved from the SisPorto system for cardiotocogram analysis and nonlinear measures were used to predict labor in a dataset of 1072 antepartum tracings, at between 30 and 35 weeks of gestation. Two groups were defined: Group A-fetuses whose traces date was less than one or two weeks before labor, and Group B-fetuses whose traces date was at least one or two weeks before labor. Results suggest that, compared with linear features such as decelerations and variability indices, compression improves labor prediction both within one (C-Statistics of 0.728) and two weeks (C-Statistics of 0.704). Moreover, the correlation between compression and long-term variability was significantly different in groups A and B, denoting that compression and heart rate variability look at different information associated with whether the fetus is closer to or further from labor onset. Nonlinear measures, compression in particular, may be useful in improving labor prediction as a complement to other fetal heart rate features.

Zwitterionization of glycine in water environment: Stabilization mechanism and NMR spectral signatures.

At physiological conditions, myriads of biomolecules (e.g., amino acids, peptides, and proteins) exist predominantly in the zwitterionic structural form and their biological functions will result in these conditions. However these geometrical structures are inaccessible energetically in the gas phase, and at this point, stabilization of amino-acids in physiological conditions is still under debate. In this paper, the electronic properties of a glycine molecule in the liquid environment were studied by performing a relaxation of the glycine geometry in liquid water using the free energy gradient method combined with a sequential quantum mechanics/molecular mechanics approach. A series of Monte Carlo Metropolis simulations of the glycine molecule embedded in liquid water, followed by only a quantum mechanical calculation in each of them were carried out. Both the local and global liquid environments were emphasized to obtain nuclear magnetic resonance (NMR) parameters for the glycine molecule in liquid water. The results of the equilibrium structure in solution and the systematic study of the hydrogen bonds were used to discard the direct proton transfer from the carboxyl group to the ammonium group of the glycine molecule in water solution. The calculations of the Density Functional Theory (DFT) were performed to study the polarization of the solvent in the parameters of nuclear magnetic resonance of the glycine molecule in liquid water. DFT calculations predicted isotropic chemical changes on the H, C, N, and O atoms of glycine in liquid water solution which agree with the available experimental data.

Longitudinal changes of cardiotocographic parameters throughout pregnancy: a prospective cohort study comparing small-for-gestational-age and normal fetuses from 24 to 40 weeks.

OBJECTIVE: To compare longitudinal trends of cardiotocographic (CTG) parameters between small-for-gestational-age (SGA) and normal fetuses, from 24 to 41 weeks of pregnancy. METHODS: A prospective cohort study was carried out in singleton pregnancies without fetal malformations. At least one CTG was performed in each of the following intervals: 24-26 weeks+6 days, 27-29 weeks+6 days, 30-32 weeks+6 days, 33-35 weeks+6 days, 36-38 weeks+6 days and ≥39 weeks. Tracings were analyzed using the Omniview-SisPorto® 3.6 system. Cases with a normal pregnancy outcome, including a birthweight ≥10th percentile for gestational age, were compared with two groups of SGA fetuses: with birthweight <10th percentile (SGA

Cardiotocographic parameters in small-for-gestational-age fetuses: How do they vary from normal at different gestational ages? A study of 11687 fetuses from 25 to 40 weeks of pregnancy.

AIM: The aim of this study was to assess how cardiotocographic (CTG) parameters differ between small-for-gestational-age (SGA) and normal fetuses at different gestational ages. METHODS: This was a retrospective cross-sectional study using the first antepartum tracing of singleton pregnancies with no malformations. Fetuses with birthweight ≥10th percentile for gestational age and other normal pregnancy outcome criteria (term birth, normal umbilical artery pH and Apgar scores, no intensive care unit admission) were compared with fetuses with birthweight <10th and <3rd percentiles for gestational age (SGA < p10 and SGA < p3, a subgroup of the latter). Each CTG parameter was compared, by gestational age, using both statistical tests and percentile curves derived from normal outcome cases. Tracings were analyzed with the OmniviewSisPorto® 3.7 system. RESULTS: A total of 11 687 tracings (from the same number of fetuses) were analyzed: 9701 normal, 1986 SGA < p10, and 543 SGA < p3. SGA fetuses had lower long- and short-term variability, and number of accelerations, with more pronounced differences between around 28 and 35 weeks. In contrast, baseline was lower in SGA fetuses from 34 weeks onwards. All differences were more pronounced for SGA < p3 fetuses. Similar trends throughout gestation occurred in all groups: decrease in baseline, and increase in long- and short-term variability, and accelerations. CONCLUSIONS: This study represents an important step for accurate CTG interpretation in SGA fetuses and, consequently, management of fetal growth restriction (FGR), as it contributes to differentiate between maturational CTG changes that occur physiologically throughout pregnancy, and possible signs of fetal compromise in FGR.

Longitudinal evaluation of computerized cardiotocographic parameters throughout pregnancy in normal fetuses: a prospective cohort study.

INTRODUCTION: The longitudinal cardiotocographic (CTG) changes throughout pregnancy in normal fetuses have never been fully described. We aimed at characterizing the evolution of CTG parameters in healthy fetuses, from 24 to 41 weeks of gestation. MATERIAL AND METHODS: A prospective cohort study was conducted in singleton fetuses without structural abnormalities on second-trimester ultrasound. At least one CTG was performed in each of the following intervals: 24-26 weeks(+6d) , 27-29 weeks(+6d) , 30-32 weeks(+6d) , 33-35 weeks(+6d) , 36-38 weeks(+6d) and ≥39 weeks; tracings were analyzed by the OMNIVIEW-SISPORTO 3.6 system. Cases of preterm delivery, fetal death, birthweight under the 10th percentile, low five-minute Apgar, umbilical artery acidemia or neonatal intensive care unit admission were subsequently excluded. RESULTS: A total of 1049 eligible tracings were obtained from 145 fetuses. There was a significant increase over time in average long-term variability (LTV), average short-term variability (STV), number of accelerations and uterine contractions. Conversely, fetal heart rate (FHR) baseline and number of decelerations decreased. A high inter-fetal variability was observed, but there was considerable intra-fetal consistency. Fetuses showing a marked decrease in FHR baseline and those with a marked increase in average LTV had a significantly lower birthweight. Cesarean section rate was significantly higher in cases with a decrease in average STV throughout gestation. CONCLUSIONS: This prospective longitudinal study shows an evolution in computerized CTG parameters during pregnancy, indicating the need to adapt interpretation criteria based on gestational age. The high inter-fetal variability and considerable intra-fetal consistency suggests the possible value of using each fetus as its own reference in serial assessments.

Laparoscopic-assisted Retropubic Midurethral Sling Placement: A Technique to Avoid Major Complications.

STUDY OBJECTIVE: To describe a technique for the safe placement of retropubic midurethral slings in patients undergoing concomitant laparoscopic surgery in order to avoid major complications associated with this procedure such as bladder perforation and retropubic hematomas. DESIGN: Step-by-step video demonstration of the technique. SETTING: A university tertiary care hospital. PATIENTS: Patients with an indication for retropubic midurethral sling placement because of recurrent stress urinary incontinence, intrinsic sphincter deficiency, or severe pelvic organ prolapse in whom a concomitant laparoscopic surgery has to be performed for other medical conditions. INTERVENTION: Laparoscopic opening and dissection of the Retzius space and insertion of the sling under a laparoscopic view of this space. MEASUREMENTS AND MAIN RESULTS: This technique has been mainly used in patients undergoing laparoscopic pelvic organ prolapse repair. No complications have been identified so far, even in high-risk patients such as those with previous Burch colposuspension. CONCLUSION: This is a simple and reproducible technique for preventing major complications associated with retropubic sling placement in patients undergoing laparoscopic surgery for other reasons. It also permits the immediate detection and even resolution of complications in case any arise. Even high-risk patients may be safely approached.

Laparoscopy-like operative vaginoscopy: a new approach to manage mesh erosions.

STUDY OBJECTIVE: Mesh erosion through the vagina is the most common complication of synthetic mesh used for pelvic organ prolapse repair. However, conventional transvaginal mesh excision has many technical limitations. We aimed at creating and describing a new surgical technique for transvaginal removal of exposed mesh that would enable better exposition and access, thus facilitating optimal treatment. DESIGN: A step-by-step video showing the technique. SETTING: A university tertiary care hospital. PATIENTS: Five patients previously submitted to pelvic organ prolapse repair using synthetic mesh, presenting mesh erosion through the vagina. INTERVENTIONS: Mesh excision using a laparoscopy-like operative vaginoscopy in which standard laparoscopic instruments are used through a single-incision laparoscopic surgery port device placed in the vagina. MEASUREMENTS AND MAIN RESULTS: In all cases, a very good exposure of the mesh was achieved, a minimal tissue traction was required, and the procedures were performed in a very ergonomic way. All the patients were discharged on the same day of the surgery and had a painless postoperative course. So far, there have been no cases of relapse. CONCLUSION: This seems to be a simple, cheap, and valuable minimally invasive technique with many advantages in comparison with the conventional approach. More cases and time are necessary to access its long-term efficacy. It may possibly be used for the management of other conditions.

Strategies to Assess the Impact of Sustainable Functional Food Ingredients on Gut Microbiota.

Nowadays, it is evident that food ingredients have different roles and distinct health benefits to the consumer. Over the past years, the interest in functional foods, especially those targeting gut health, has grown significantly. The use of industrial byproducts as a source of new functional and sustainable ingredients as a response to such demands has raised interest. However, the properties of these ingredients can be affected once incorporated into different food matrices. Therefore, when searching for the least costly and most suitable, beneficial, and sustainable formulations, it is necessary to understand how such ingredients perform when supplemented in different food matrices and how they impact the host's health. As proposed in this manuscript, the ingredients' properties can be first evaluated using in vitro gastrointestinal tract (GIT) simulation models prior to validation through human clinical trials. In vitro models are powerful tools that mimic the physicochemical and physiological conditions of the GIT, enabling prediction of the potentials of functional ingredients per se and when incorporated into a food matrix. Understanding how newly developed ingredients from undervalued agro-industrial sources behave as supplements supports the development of new and more sustainable functional foods while scientifically backing up health-benefits claims.

Omalizumab in Chronic Spontaneous Urticaria (CSU): Real-Life Experience in Dose/Interval Adjustments and Treatment Discontinuation.

BACKGROUND: Data on real-life experience with omalizumab dose/interval adjustments are still limited, as well as on omalizumab discontinuation. OBJECTIVE: To evaluate efficacy and safety of omalizumab dose/interval adjustment in a Portuguese cohort of patients with chronic spontaneous urticaria (CSU) and to characterize those who discontinued omalizumab. METHODS: A retrospective study of patients who started omalizumab for CSU at a Portuguese Urticaria Center of Reference and Excellence (UCARE) was conducted between 2009 and 2021. Response criteria were based on a weekly Urticaria Activity Score (UAS7) <7 points (partial: UAS7 7-15 points; nonresponders: UAS7 >15 points) and minimal important difference >10 points. RESULTS: A total of 138 patients were enrolled in the study; 83% of them were women, and the median age was 49 years (interquartile range: 40-58 years). On 300 mg q4 weeks, 96 (70%) patients were responders, 29 (21%) partial responders, and 13 (9%) nonresponders. After dose/interval adjustments (up to 600 mg q2 weeks), 108 (78%) were responders, 27 (20%) partial responders, and 3 (2%) nonresponders. No adverse events were reported. Updosing was more frequent in patients with angioedema, body mass index >30 kg/m2, positive basophil activation test, and autologous serum test. A total of 71 (51%) patients lengthened interval, presenting higher median pre-omalizumab D-dimer (0.2 vs 0 mcg/mL, P = .038) and C-reactive protein (0.3 vs 0.1 mg/dL, P = .030) values than those with a standard dose. In total, 37 patients (27%) stopped omalizumab, but 14 (38%) of them needed retreatment on average 11 months after discontinuation. Patients with angioedema and a longer omalizumab duration had higher chance of relapse. CONCLUSIONS: Omalizumab dose and/or interval adjustment is effective and safe and should be implemented in partial/nonresponders for response improvement and in responders for further discontinuation. A protocol for regimen adjustments is proposed.

Modulation of the Gut Microbiota by Tomato Flours Obtained after Conventional and Ohmic Heating Extraction and Its Prebiotic Properties.

Several studies have supported the positive functional health effects of both prebiotics and probiotics on gut microbiota. Among these, the selective growth of beneficial bacteria due to the use of prebiotics and bioactive compounds as an energy and carbon source is critical to promote the development of healthy microbiota within the human gut. The present work aimed to assess the fermentability of tomato flour obtained after ohmic (SFOH) and conventional (SFCONV) extraction of phenolic compounds and carotenoids as well as their potential impact upon specific microbiota groups. To accomplish this, the attained bagasse flour was submitted to an in vitro simulation of gastrointestinal digestion before its potential fermentability and impact upon gut microbiota (using an in vitro fecal fermentation model). Different impacts on the probiotic strains studied were observed for SFCONV promoting the B. animalis growth, while SFOH promoted the B. longum, probably based on the different carbohydrate profiles of the flours. Overall, the flours used were capable of functioning as a direct substrate to support potential prebiotic growth for Bifidus longum. The fecal fermentation model results showed the highest Bacteroidetes growth with SFOH and the highest values of Bacteroides with SFCONV. A correlation between microorganisms' growth and short-chain fatty acids was also found. This by-product seems to promote beneficial effects on microbiota flora and could be a potential prebiotic ingredient, although more extensive in vivo trials would be necessary to confirm this.

Radioiodine therapy during the COVID-19 pandemic in a public reference hospital in Brazil: an experience report.

COVID-2019 has resulted in an emerging respiratory infection that has spread as a pandemic since January 2020. Nuclear Medicine Services and its workers experienced a dramatic change in their clinical routine. They were required to adjust protocols for this new health condition. Regarding radioiodine therapy (RIT), initial orientations were to postpone treatments. In Brazil, National Nuclear Energy Commission prepared guidelines. It authorized RIT to employ activities over 1850 MBq in an outpatient setting on an exceptional basis. This study reports the RIT experience of a Brazilian hospital during the COVID-19 pandemic, intending to evaluate the applicability of outpatient treatment employing over 1850 MBq of I-131 on a large scale. During referred period, 106 patients at our service had an indication for RIT, of which 58 agreed to participate in the research and provided informed consent. Majority of patients did not meet the minimum requirements for outpatient treatment using doses > 1850 MBq.