Impact of an online course on enhancing the diagnosis of Chagas disease in Latin America.

Objective: Chagas disease poses a public health problem in Latin America, and the electrocardiogram is a crucial tool in the diagnosis and monitoring of this pathology. In this context, the aim of this study was to quantify the change in the ability to detect electrocardiographic patterns among healthcare professionals after completing a virtual course. Materials and Methods: An asynchronous virtual course with seven pre-recorded classes was conducted. Participants answered the same questionnaire at the beginning and end of the training. Based on these responses, pre and post-test results for each participant were compared. Results: The study included 1656 participants from 21 countries; 87.9% were physicians, 5.2% nurses, 4.1% technicians, and 2.8% medical students. Initially, 3.1% answered at least 50% of the pre-test questions correctly, a proportion that increased to 50.4% after the course (p=0.001). Regardless of their baseline characteristics, 82.1% of course attendees improved their answers after completing the course. Conclusions: The implementation of an asynchronous online course on electrocardiography in Chagas disease enhanced the skills of both medical and non-medical personnel to recognize this condition.

Evaluating the diagnostic performance of Liaison® chemiluminescence assay as screening tool for detection of acute Epstein-Barr infection: A comparative study.

The present investigation assessed the Liaison® diagnostic performance in detecting Epstein-Barr (EBV) IgM-VCA in a large patient cohort, considering age and symptomatology. VIDAS® were employed as a benchmark for acute EBV infection. The study also probed other coexisting conditions and potential cross-reactivity for error sources. A total of 1311 samples were analyzed, with notable associations found only among paediatric (kappa=0.75) and young adult (kappa=0.58) populations with compatible symptoms. ROC analysis revealed varying optimal cutoff values based on age and symptom categorizations. Logistic regression models identified age and patients from Oncology or Infectious Disease as significant factors for false positives. Potential interferences emerged with RF, ANCA, cytomegalovirus-IgM and VHS-IgM. Notably, Liaison® couldn´t distinguish EBV patients from Oncology, Haemathology or Internal Medicine. This study provides valuable insights, such as implementing ageand symptom-specific thresholds or reviewing test requests, for optimizing EBV serology in microbiology laboratories, leading to faster and more reliable responses.

From Castleman disease histopathological features to idiopathic multicentric Castleman disease: a multiparametric approach to exclude potential iMCD histopathological mimickers.

AIMS: International consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) includes lymph node Castleman disease (CD) histopathological features as major criteria. Our aim was to apply those criteria in a series of 42 cases with CD to find differences among unicentric CD, iMCD, HHV-8+multicentric CD (HHV-8+MCD) and POEMS/plasma cell neoplasia (PCN)-associated CD. METHODS: Available clinical and laboratory criteria were collected. Histopathological features (germinal centre hyperplasia/regression, plasmacytosis, hypervascularity and follicular dendritic cell (FDC) prominence) were graded and immunohistochemistry with antibodies against CD20, CD3, CD138, HHV-8, Ig isotype (IgG, IgG4, IgA, IgM, IgD), kappa, lambda was performed in all cases. RESULTS: Fourteen cases had hyaline-vascular type unicentric CD, 15 were HHV-8+MCD, 7 cases PCN/POEMS-associated CD and 5 cases were iMCD. One case was consistent with systemic lupus erythematosus (SLE) lymphadenopathy. Differences in grading of the CD-associated histopathological features showed that FDC proliferation was prominent in unicentric CD, hypervascularity was increased in HHV-8 positive MCD and germinal centre hyperplasia was restricted to iMCD cases and SLE. Monotypic plasma cells were readily identifiable in the lymph node biopsies in 43% of PCN/POEMS-associated CD. All three cases had lambda light chain restriction with IgA (two cases) and IgG (one case) isotypes. CONCLUSIONS: HHV-8+ MCD and PCN/POEMS-related CD are the major mimickers of iMCD in lymph node biopsies. Grading of the five histopathological features for CD might be useful to, in conjunction with complete ancillary testing, suggest for specific disease entities.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Use of sera cell free DNA (cfDNA) and exovesicle-DNA for the molecular diagnosis of chronic Chagas disease.

Chagas disease, a neglected tropical disease, is now considered a worldwide health concern as a result of migratory movements from Central and South America to other regions that were considered free of the disease, and where the epidemiological risk is limited to transplacental transmission or blood or organ donations from infected persons. Parasite detection in chronically ill patients is restricted to serological tests that only determine infection by previous infection and not the presence of the parasite, especially in patients undergoing treatment evaluation or in newborns. We have evaluated the use of nucleic acids from both circulating exovesicles and cell-free DNA (cfDNA) from 50 samples twice randomly selected from a total of 448 serum samples from immunologically diagnosed patients in whom the presence of the parasite was confirmed by nested PCR on amplicons resulting from amplification with kinetoplastid DNA-specific primers 121F-122R. Six samples were randomly selected to quantify the limit of detection by qPCR in serum exovesicles. When the nucleic acids thus purified were assayed as a template and amplified with kinetoplastid DNA and nuclear satellite DNA primers, a 100% positivity rate was obtained for all positive samples assayed with kDNA-specific primers and 96% when SAT primers were used. However, isolation of cfDNA for Trypanosoma cruzi and amplification with SAT also showed 100% positivity. The results demonstrate that serum exovesicles contain DNA of mitochondrial and nuclear origin, which can be considered a mixed population of exovesicles of parasitic origin. The results obtained with serum samples prove that both cfDNA and Exovesicle DNA can be used to confirm parasitaemia in chronically ill patients or in samples where it is necessary to demonstrate the active presence of the parasite. The results confirm for the first time the existence of exovesicles of mitochondrial origin of the parasite in the serum of those affected by Chagas disease.

Starkeya nomas sp. nov., a prosthecate and budding bacterium isolated from an immunocompromized patient.

Strain HF14-78462T is an environmental bacterium found in clinical samples from an immunocompromized patient in 2014 at Hospital Universitari i Politècnic La Fe (Valencia, Spain). Phenotypically, strain HF14-78462T cells were Gram-stain-negative, aerobic, non-spore forming and non-motile small rods which formed mucous and whitish-translucent colonies when incubated at 20-36 °C. Phylogenetic analyses based on the 16S rRNA genes and the whole genomes of closest sequenced relatives confirmed that strain HF14-78462T is affiliated with the genus Starkeya. The strain was oxidase, catalase and urease positive; but indole, lysine decarboxylase, ornithine decarboxylase and DNase negative, did not produce H2S and was able to utilize a wide variety of carbon sources including acetamide, adonitol, amygdalin, l-arabinose, citric acid, glucose, mannitol and melibiose. Unlike Starkeya novella and Starkeya koreensis, strain HF14-78462T failed to grow in thiosulphate-oxidizing media and had a narrower temperature growth range. Its genome was characterized by a size of 4.83 Mbp and a C+G content of 67.75 mol%. Major fatty acids were C18:1 ω7c, cyclo C19 : 0 and C16 : 0, its polar acids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an aminophospholipid; while the ubiquinones were Q9 (1.8 %) and Q10 (98.2 %). Digital DNA-DNA hybridization values were 41 and 41.4 against S. novella and S. koreensis, respectively, while average nucleotide identity values were around 84 %. Phenotypic, average nucleotide identity and phylogenomic comparative studies suggest that strain HF14-78462T is a new representative of the genus Starkeya and the name Starkeya nomas sp. nov. is proposed. The type strain is HF14-78462T (=CECT 30124T=LMG 31874T).

Energy metabolism of juvenile scallops Nodipecten subnodosus under acute increased temperature and low oxygen availability.

High temperature increases energy demand in ectotherms, limiting their physiological capability to cope with hypoxic events. The present study aimed to assess the metabolic tolerance of juvenile Nodipecten subnodosus scallops to acute hyperthermia combined with moderate hypoxia. A previous study showed that juveniles exhibited a high upper temperature limit (32 °C), but the responses of juveniles to combined hyperthermia and low dissolved oxygen are unknown. Scallops were exposed to control conditions (treatment C: 22 °C, ∼7.1 mg O2 L-1 or PO2 156.9 mmHg), acute hyperthermia under normoxia (treatment T: 30 °C, ∼6.0 mg O2 L-1 or PO2 150.9 mmHg) or acute hyperthermia plus hypoxia (treatment TH: 30 °C, ∼2.5 mg O2 L-1 or PO2 62.5 mmHg) for 18 h. In T, juveniles exhibited an enhanced oxygen consumption, together with a decrease in adenylate energy charge (AEC) and arginine phosphate (ArgP), and with no changes in metabolic enzyme activity in the muscle. In TH, scallops maintained similar AEC and ArgP levels in muscle as those observed in T treatment. This response occurred along with the accumulation of inosine monophosphate and hypoxanthine. Besides, reduced citrate synthase and pyruvate kinase activities, enhanced hexokinase activity, and a higher octopine dehydrogenase/lactate dehydrogenase ratio in the mantle indicated the onset of anaerobiosis in TH. These responses indicate that juvenile scallops showed tissue-specific compensatory responses regarding their energy balance under moderate hypoxia at high temperatures. Our results give an insight into the tolerance limit of this species to combined hyperthermia and hypoxia in its northern limit of distribution.

IgG antibody response to pneumococcal-conjugated vaccine (Prevenar®13) in children with immunodeficiency disorders.

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab.

INTRODUCTION: Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. METHODS: This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. RESULTS: In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). CONCLUSION: Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.

Mortality related to COVID-19 in patients with rheumatic and musculoskeletal diseases, first wave of the outbreak: a single-center study.

Objectives: The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk. Methods: An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable - type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI. Results: Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96-92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64-2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1-5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model. Conclusion: In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic. Plain Language Summaries: Mortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseases Why was this study done? - To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19. What did the researchers do? - We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain. What did the researchers find? - In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19- In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk- Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly. What do the findings mean? - The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management.

Security of 3D-printed polylactide acid piece sterilization in the operating room: a sterility test.

INTRODUCTION: 3D-printing technology has become very popular the last 10 years, and their advantages have been widely proved. However, its safety in the operating room after sterilization has not been evaluated. Thus, the use of 3D printing is still questioned. The aim of this work is to evaluate the security of polylactic acid (PLA) to print surgical models after its sterilization. MATERIALS AND METHODS: One hundred and eighty-six PLA plates and 6 negative controls without microorganisms were seeded. After 10 days of culture, the PLA plates were randomized into three groups: A, B, and C. Group A underwent a sterilization process using an autoclave program at 134 °C. Group B was seeded in different culture media and group C was used to make crystal violet stains on the biofilms formed on the PLA. Mechanical properties of PLA after autoclave sterilization including, the breaking load, deformation and breaking load per surface were calculated. RESULTS: Hundred percent of the group B showed monomicrobial growth. Stains performed on group C PLA showed biofilms in all PLA pieces. After sterilization, no pathogen growth was observed in group A during the culture observation period showing 100% sterilization effectiveness. A filling percentage of 5% obtained a breaking load of 6.36 MPa, and its elastic limit occurred after an elongation of 167.4%. A 10% infill was mechanically safe. CONCLUSIONS: Autoclave sterilization of PLA-printed pieces is safe for the patient and mechanically strong for the surgeon. This is the first 3D-printing protocol described and evaluated to implement 3D-printing technology safely in the operating room. SIGNIFICANCE AND IMPACT OF STUDY: This is the first 3D-printing protocol described to print and sterilize 3D biomodels using an autoclave showing its biological safety and its mechanical resistance.

Autoclave sterilization of an in-house 3D-printed polylactic acid piece: biological safety and heat-induced deformation.

AIMS: Fused filament fabrication 3D printing with polylactic acid filaments is the most widely used method to generate biomodels at hospitals throughout the world. The main limitation of this manufacturing system is related to the biomodels' temperature sensitivity, which all but prevents them to be sterilized using conventional methods. The purpose of this study is to define an autoclave temperature-resistant FFF-PLA 3D printing protocol to print 3D fractures biomodels during preoperative planning. METHODS AND RESULTS: Six different printing protocols were established, each with a different infill percentage. Ten distal radius biomodels were printed with each protocol and each biomodel was subject to 3D scanning. The biomodels were subsequently autoclave-sterilized at 134 °C and subjected to a new scanning process, which was followed by a calculation of changes in area, volume and deformity using the Hausdorff-Besicovitch method. Finally, 192 polylactic acid models were produced using the printing protocol offering the greatest resistance and were contaminated with 31 common nosocomial pathogens to evaluate the effectiveness of sterilizing the model printed using the said protocol. Sterilization resulted in a mean deformation of the biomodel of 0.14 mm, a maximum deformity of 0.75 mm, and a 1% area and a 3.6% volume reduction. Sterilization of the pieces printed using the analyzed protocol was 100% effective. CONCLUSIONS: The analyzed 3D printing protocol may be applied with any FFF-PLA 3D printer, it is safe and does not significantly alter the morphology of biomodels. These results indicate that 3D printing is associated with significant advantages for health centers as it increases their autonomy, allowing them to easily produce 3D biomodels that can be used for the treatment of fractures.

Psychedelics, Sociality, and Human Evolution.

Our hominin ancestors inevitably encountered and likely ingested psychedelic mushrooms throughout their evolutionary history. This assertion is supported by current understanding of: early hominins' paleodiet and paleoecology; primate phylogeny of mycophagical and self-medicative behaviors; and the biogeography of psilocybin-containing fungi. These lines of evidence indicate mushrooms (including bioactive species) have been a relevant resource since the Pliocene, when hominins intensified exploitation of forest floor foods. Psilocybin and similar psychedelics that primarily target the serotonin 2A receptor subtype stimulate an active coping strategy response that may provide an enhanced capacity for adaptive changes through a flexible and associative mode of cognition. Such psychedelics also alter emotional processing, self-regulation, and social behavior, often having enduring effects on individual and group well-being and sociality. A homeostatic and drug instrumentalization perspective suggests that incidental inclusion of psychedelics in the diet of hominins, and their eventual addition to rituals and institutions of early humans could have conferred selective advantages. Hominin evolution occurred in an ever-changing, and at times quickly changing, environmental landscape and entailed advancement into a socio-cognitive niche, i.e., the development of a socially interdependent lifeway based on reasoning, cooperative communication, and social learning. In this context, psychedelics' effects in enhancing sociality, imagination, eloquence, and suggestibility may have increased adaptability and fitness. We present interdisciplinary evidence for a model of psychedelic instrumentalization focused on four interrelated instrumentalization goals: management of psychological distress and treatment of health problems; enhanced social interaction and interpersonal relations; facilitation of collective ritual and religious activities; and enhanced group decision-making. The socio-cognitive niche was simultaneously a selection pressure and an adaptive response, and was partially constructed by hominins through their activities and their choices. Therefore, the evolutionary scenario put forward suggests that integration of psilocybin into ancient diet, communal practice, and proto-religious activity may have enhanced hominin response to the socio-cognitive niche, while also aiding in its creation. In particular, the interpersonal and prosocial effects of psilocybin may have mediated the expansion of social bonding mechanisms such as laughter, music, storytelling, and religion, imposing a systematic bias on the selective environment that favored selection for prosociality in our lineage.

Prospective cohort study on hospitalised patients with suspected urinary tract infection and risk factors por multidrug resistance.

Urinary tract infections (UTIs) are among the most common bacterial infections and a frequent cause for hospitalization in the elderly. The aim of our study was to analyse epidemiological, microbiological, therapeutic, and prognostic of elderly hospitalised patients with and to determine independent risk factors for multidrug resistance and its outcome implications. A single-centre observational prospective cohort analysis of 163 adult patients hospitalized for suspected symptomatic UTI in the Departments of Internal Medicine, Infectious Diseases and Short-Stay Medical Unit of a tertiary hospital was conducted. Most patients currently admitted to hospital for UTI are elderly and usually present high comorbidity and severe dependence. More than 55% met sepsis criteria but presented with atypical symptoms. Usual risk factors for multidrug resistant pathogens were frequent. Almost one out of five patients had been hospitalized in the 90 days prior to the current admission and over 40% of patients had been treated with antibiotic in the previous 90 days. Infection by MDR bacteria was independently associated with the previous stay in nursing homes or long-term care facilities (LTCF) (OR 5.8, 95% CI 1.17-29.00), permanent bladder catheter (OR 3.55, 95% CI 1.00-12.50) and urinary incontinence (OR 2.63, 95% CI 1.04-6.68). The degree of dependence and comorbidity, female sex, obesity, and bacteraemia were independent predictors of longer hospital stay. The epidemiology and presentation of UTIs requiring hospitalisation is changing over time. Attention should be paid to improve management of urinary incontinence, judicious catheterisation, and antibiotic therapy.

Oral immunotherapy in severe cow's milk allergic patients treated with omalizumab: Real life survey from a Spanish registry.

BACKGROUND: Oral immunotherapy is a frequent treatment for the management of food allergies, but adverse events (AE) are common. This study assessed the outcome of cow's milk oral immunotherapy (MOIT) in severe cow`s milk-allergic patients treated with omalizumab in a real-life setting. METHODS: OmaBASE was a national, multicenter, open, and observational registry that collected clinical, immunologic, and treatment from patients with food allergy receiving omalizumab. RESULTS: Data derived from 58 patients aged 10.3 years (IQR 6.3-13.2) and median milk-specific IgE 100 kUA /L at the start of omalizumab treatment. Most had experienced anaphylaxis by accidental exposures (70.7%) and had asthma (81.0%). Omalizumab in monotherapy induced tolerance to ≥6000 mg of cow's milk protein (CMP) to 34.8% of patients tested by oral food challenge. Omalizumab combined with MOIT conferred desensitization to ≥6000 mg of CMP to 83.0% of patients. Omalizumab withdrawal triggered more AE (P = .013) and anaphylaxis (P = .001) than no discontinuation. Anaphylaxis was observed in 36.4% of patients who discontinued omalizumab, and more in those with sudden (50.0%) rather than progressive (12.5%) discontinuation. At database closure, 40.5% of patients who had completed follow-up tolerated CMP without omalizumab (7.2% 1500-4500 mg; 33.3% ≥6000 mg). CONCLUSION: Milk oral immunotherapy initiated under omalizumab allows the desensitization of subjects with severe cow's milk allergy even after omalizumab discontinuation. However, discontinuation of omalizumab can lead to severe AE and should be carefully monitored.