Diarrea crónica en paciente inmunocompetente / Chronic diarrhea in an immunocompetent patient

Presentamos un caso de diarrea crónica en un paciente varón de 58 años que no tenía antecedentes personales de interés ni alteraciones conocidas en su estado inmunitario. (AU)

We present a case of chronic diarrhea in a 58-year-old male patient with no relevant personal history and no known alterations in his immune status. (AU)

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Placenta Accreta in a COVID-19 positive patient

Placenta accreta spectrum is a state of abnormal attachment of the placenta to the myometrium, resulting in hemorrhage and delayed or impossible delivery of the placenta. It`s an infrequent pathology, and this condition can be life-threatening. We present an interesting case of a 41-year-old female with COVID-19 that attends the emergency room due to scanty vaginal bleeding at 14 days postpartum. A hemostatic hysterectomy was performed, and the diagnosis of placenta accreta was made. (AU)

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes.

Five biological drugs are currently marketed for treatment of uncontrolled severe asthma. They all block type 2 inflammatory pathways by targeting IgE (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), or the IL-4/IL-13 pathway (dupilumab). Hypereosinophilia has been observed in 4%-25% of patients treated with dupilumab and is transient in most cases, although there have been reports of persistent cases of symptomatic hypereosinophilia consistent with eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia, eosinophilic vasculitis, and sudden worsening of asthma symptoms. Cases of EGPA have been reported with all biologics, including anti-IL-5 agents, and with leukotriene receptor antagonists in publications or in the EudraVigilance database. In many cases, EGPA appears during tapering of systemic corticosteroids or after switching from an anti-IL-5 biologic to dupilumab, suggesting that systemic corticosteroids or the anti-IL-5 agent were masking vasculitis. This review investigates plausible mechanisms of dupilumab-induced hypereosinophilia and review cases of symptomatic hypereosinophilia associated with dupilumab. Blockade of the IL-4/IL-13 pathway reduces eosinophil migration and accumulation of blood by inhibiting eotaxin-3, VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in bone marrow. When choosing the optimal biologic, it seems necessary to consider the presence of hypereosinophilia (>1500/µL), in which case an anti-IL-5/IL-5R agent is preferable. Furthermore, when switching from an anti-IL-5/5R to an anti-IL-4/13R agent, blood eosinophils and clinical progress should be closely monitored. Nevertheless, dual therapy with anti-IL-5/5R and anti-IL4/IL-13R agents may be needed for optimal control, since both the IL-5 and the IL-4/IL-13 pathways can simultaneously contribute to airway inflammation. This approach can prevent the development of EGPA and other types of symptomatic hypereosinophilia while maintaining control of nasal polyposis. In the near future, it will be possible to use a new generation of biological therapies for the treatment of severe asthma. These act at a higher level of the inflammatory cascade, as is the case of the antialarmins tezepelumab and itepekimab.

Serum microRNAs Catalog Asthma Patients by Phenotype.

BACKGROUND AND OBJECTIVES: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. METHODS: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. RESULTS: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. CONCLUSIONS: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Five biological drugs are currently marketed for treatment of uncontrolled severe asthma. They all block type 2 inflammatory pathways by targeting IgE (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), or the IL-4/IL-13 pathway (dupilumab). Hypereosinophilia has been observed in 4%-25% of patients treated with dupilumab and is transient in most cases, although there have been reports of persistent cases of symptomatic hypereosinophilia consistent with eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia, eosinophilic vasculitis, and sudden worsening of asthma symptoms. Cases of EGPA have been reported with all biologics, including anti–IL-5 agents, and with leukotriene receptor antagonists in publications or in the EudraVigilance database. In many cases, EGPA appears during tapering of systemic corticosteroids or after switching from an anti–IL-5 biologic to dupilumab, suggesting that systemic corticosteroids or the anti–IL-5 agent were masking vasculitis. This review investigates plausible mechanisms of dupilumab-induced hypereosinophilia and review cases of symptomatic hypereosinophilia associated with dupilumab. Blockade of the IL-4/IL-13 pathway reduces eosinophil migration and accumulation of blood by inhibiting eotaxin-3, VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in bone marrow. When choosing the optimal biologic, it seems necessary to consider the presence of hypereosinophilia (>1500/μL), in which case an anti–IL-5/IL-5R agent its preferable.Furthermore, when switching from an anti–IL-5/5R to an anti–IL-4/13R agent, blood eosinophils and clinical progress should be closely monitored. Nevertheless, dual therapy with anti–IL-5/5R and anti–IL4/IL-13R agents may be needed for optimal control, since both the IL-5 and the IL-4/IL-13 pathways can simultaneously contribute to airway inflammation. This approach can prevent the development of EGPA and other types of

Actualmente se dispone de cinco fármacos biológicos para el tratamiento del asma grave no controlada de tipo T2. Todos ellos,bloquean las vías inflamatorias de tipo 2, ya sea dirigiéndose a la vía de la IgE (omalizumab), la vía de la IL-5 (mepolizumab, reslizumab,benralizumab) o la vía de la IL-4/13 (dupilumab). Se ha descrito que, entre el 4% y el 25% de los pacientes tratados con dupilumabdesarrollan hipereosinofilia, la cual es benigna y transitoria en la mayoría de los casos, aunque una minoría de pacientes presentan unahipereosinofilia persistente y acompañada de sintomatología clínica que varía desde la granulomatosis eosinofílica con poliangitis (GEPA),a la neumonía eosinofílica, la vasculitis eosinofílica o el empeoramiento repentino de los síntomas del asma. Se han comunicado casosde GEPA con todos los productos biológicos, incluidos los anti-IL-5, y con antagonistas de los receptores de leucotrienos, bien en formade casos clínicos o pequeñas series publicadas, o bien en la base de datos de farmacovigilancia de la Agencia Europea del Medicamento(EMA) EudraVigilance. En muchos de estos pacientes, la GEPA aparece durante la reducción gradual de los esteroides sistémicos o despuésde cambiar de un biológico anti-IL-5 a dupilumab, por fallo terapéutico, lo cual sugiere que los esteroides sistémicos o los anti-IL-5estaban enmascarando la vasculitis. Sin embargo, otros casos no pueden explicarse por la interpretación anterior, pudiendo deducirsecomo una consecuencia directa del uso del biológico. Esta revisión tiene como objetivo corroborar los mecanismos plausibles de lahipereosinofilia inducida por dupilumab y revisar la GEPA y otros casos de hipereosinofilia sintomática presumiblemente asociados conla terapia con dupilumab. El bloqueo de la vía IL-4/IL-13 puede causar una reducción de la migración de eosinófilos y su acumulaciónen sangre periférica, al inhibir la eotaxina-3, VCAM-1 y TARC sin inhibir simultáneamente la eosinofilopoyesis en la

Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19.

Eosinophils were discovered more than 140 years ago. These polymorphonuclear leukocytes have a very active metabolism and contain numerous intracellular secretory granules that enable multiple effects on both health and disease status. Classically, eosinophils have been considered important immune cells in the pathogenesis of inflammatory processes (eg, parasitic helminth infections) and allergic or pulmonary diseases (eg, asthma) and are always associated with a type 2 immune response. Furthermore, in recent years, eosinophils have been linked to the immune response by conferring host protection against fungi, bacteria, and viruses, which they recognize through several molecules, such as toll-like receptors and the retinoic acid-inducible gene 1-like receptor. The immune protection provided by eosinophils is exerted through multiple mechanisms and properties. Eosinophils contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines, and other molecules, all of which contribute to their functioning. In addition to the competence of eosinophils as effector cells, their capabilities as antigen-presenting cells enable them to act in multiple situations, thus promoting diverse aspects of the immune response. This review summarizes various aspects of eosinophil biology, with emphasis on the mechanisms used and roles played by eosinophils in host defence against viral infections and response to vaccines. The review focuses on respiratory viruses, such as the new coronavirus, SARS-CoV-2.