Mutational profile of the KIT gene and its heterogeneity in primary and metastatic melanomas.

BACKGROUND: This study investigates the mutational profile of the KIT gene in primary and metastatic melanomas, highlighting the significance of genetic heterogeneity. METHODS: This research is a retrospective cohort that includes formalin-fixed and paraffin-embedded melanoma samples obtained from Hospital São Paulo, Brazil, between the years of 1996 and 2010. The research encompasses primary melanomas of the superficial spreading (SSM) and acral lentiginous (AL) subtypes and their metastases, using next-generation sequencing to explore genetic heterogeneity. RESULTS: Despite losing 57 samples due to quality issues, 27 samples from 20 patients were analyzed, revealing a nearly equal distribution between AL and SSM subtypes. Both histological subtypes revealed KIT gene variants, including previously undescribed variants and polymorphisms, emphasizing the role of such mutations in melanoma pathogenesis and the potential for targeted therapies. Tumor heterogeneity was also observed in both histological subtypes. CONCLUSIONS: The study underscores the complexity of melanoma, driven by diverse mutational landscapes within and across tumors and advocates for personalized treatment approaches based on detailed molecular profiling. Despite limitations like sample size, this research lays the groundwork for further investigation into melanoma's genetic intricacies and therapeutic vulnerabilities.

Prevalence of sleep disorders in geriatrics: an exploratory study using sleep questionnaires.

OBJECTIVES: This study aimed to investigate the prevalence of sleep problems in older subjects, considering sex and age differences. METHODS: Subjects admitted to a geriatrics clinic underwent a medical visit and completed a battery of questionnaires assessing sleep quality, insomnia, sleep apnea risk, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), chronotype, depression and global cognition. RESULTS: Fifty-eight subjects (58.6 % women, mean age 77.36±6.07) were included. The most predominant sleep-related complaint was poor sleep quality (36.2 %), followed by sleep apnea risk (34.5 %), insomnia symptoms (25.9 %), EDS (15.5 %) and RLS (12.1 %). Older women reported more insomnia, poorer sleep quality and depressive symptoms than males. Patients aged ≥ 75 years old had more comorbidities and higher sleep apnea risk compared to those under 75 years old. CONCLUSIONS: Sleep problems are frequent in older adults, requiring their screening and treatment for possibly improving well-being and reduce the burden of neuropsychiatric and medical comorbidities.

Evaluation of Cytotoxicity and Acute Oral Toxicity of Saline Extract and Protein-Rich Fraction from Moringa oleifera Lam. Leaves.

Moringa oleifera Lam. (horseradish tree) leaves demonstrate high nutritional value, are rich in proteins, and are widely used in folk medicine and food. This study investigated the presence of secondary metabolites and antinutritional proteins in leaf extract (LE) and the protein-rich fraction (PRF) derived from M. oleifera leaves, as well as the cytotoxicity to human cells, hemolytic activity, and in vivo acute toxicity and genotoxicity in mice. The flavonoids rutin and vitexin as well as trypsin inhibitors and lectins were detected in LE and PRF. Neither sample demonstrated toxicity against human peripheral blood mononuclear cells and both showed low hemolytic action. In vivo, LE and PRF did not show antinutritional effects and caused no death. The hematological parameters of the animals in the treated group were similar to those of the control. A significant increase in the serum levels of alanine aminotransferase and a discrete leukocyte infiltration with cytoplasmic vacuolization of the hepatocytes in the liver were detected in LE-treated animals. The preparations were not genotoxic or mutagenic. This study shows that LE and PRF are not antinutritional agents and presented low acute toxicity and no genotoxicity or mutagenicity. The present study contributes to the determination of the safety of using M. oleifera leaf proteins.

Safinamide effect on sleep architecture of motor fluctuating Parkinson's disease patients: A polysomnographic rasagiline-controlled study.

INTRODUCTION: Sleep problems commonly occur in Parkinson's disease (PD) and significantly affect patients' quality of life. A possible effect on subjective sleep disturbances of monoamine oxidase-B inhibitors (MAOB-Is) has been described. METHODS: This prospective, observational, single-centre study involved 45 fluctuating PD patients complaining sleep problems as documented by the PD Sleep Scale -2nd version (PDSS-2 ≥18) starting rasagiline 1 mg/daily or safinamide 100 mg/daily, according to common clinical practice, and maintaining antiparkinsonian therapy unchanged. Polysomnography (PSG), sleep questionnaires (PDSS-2, Epworth Sleepiness Scale - ESS), and motor function were evaluated at baseline (T0) and after 4 months of treatment (T1). RESULTS: Safinamide was prescribed in thirty patients and rasagiline in fifteen patients. Both drugs induced a significant improvement in Movement Disorder Society Unified PD Rating Scale III scores. Patients treated with rasagiline showed a significant increase in stage 1 (N1) Non-REM sleep compared to T0, with no significant effects on sleep scales. Patients treated with safinamide showed a significant increase in stage 3 of Non-REM sleep and sleep efficiency and a reduction in the rate of periodic limb movements, matching a significant reduction in PDSS-2 and ESS scales compared to T0. CONCLUSION: This study showed that safinamide, in addition to having a significant effect on PD motor symptoms, like the other MAOB-Is, may exert a specific beneficial effect on subjective and objective sleep, probably driven by its dual mechanism of action, which involves both dopaminergic and glutamatergic neurotransmission.

Gender medicine and sleep disorders: from basic science to clinical research.

Several pivotal differences in sleep and sleep disorders are recognized between women and men. This is not only due to changes in hormonal balance during women's reproductive life, such as in pregnancy and menopause. Women are more likely to report insomnia and non-specific symptoms of apneas, such as fatigue or mood disturbance, compared to men. Thus, it is important for clinicians and researchers to take sex and gender differences into account when addressing sleep disorders in order to acknowledge the biology unique to women. We present a narrative review that delves into the primary sleep disorders, starting from basic science, to explore the impact of gender differences on sleep and the current status of research on women's sleep health.

Corrigendum: Leaf surfaces and neolithization - the case of Arundo donax L.

[This corrects the article DOI: 10.3389/fpls.2022.999252.].

Probiotic Almond-Fermented Beverages Processed by Ultrasound: Vegan and Non-Vegan Consumer Perceptions through Packaging.

Consumer perception of foods processed by emerging technologies has been scarcely studied. This study aimed to evaluate the perception of vegan and non-vegan consumers regarding probiotic almond-fermented beverages processed by ultrasound using the packaging of the products (pasteurized/conventional, processed by ultrasound, and processed by ultrasound with a claim on the label). A "Check All That Apply" test with emojis and the Food Technology Neophobia scale were used. The "processed by ultrasound" information did not impact the purchase intention and the perception of healthiness, safety, nutrition, environmental impact, flavor, texture, and price of the products. The claim inclusion increased the perceived acceptability and purchase intention and improved the emotional profile. The vegan consumers showed a more positive perception of ultrasound processing, resulting in increased perceived acceptability, higher citation frequency of positive emoji, and lower sums for the neophobia scale. Vegan and non-vegan consumers agreed that the most important attributes for consumer acceptance are almond aroma, flavor, and consistency. In conclusion, the "processed by ultrasound" information did not negatively impact the acceptability and emotional profile of probiotic almond-fermented beverages, and using a claim on the label may improve consumer perception of the products.

Childhood obesity is associated with a high degree of metabolic disturbance in children from Brazilian semi-arid region.

Projected to impact 310 million children by the next decade, childhood obesity is linked to serious health issues like metabolic disturbance and cardiovascular diseases. This study introduces a novel approach for the integrated assessment of inflammatory, glycemic and lipid disorders in obese children in resources-limited settings and also identifies key factors contributing to these changes. Conducting a cross-sectional analysis of 231 children aged 5-12 years from public schools in Brazil's semi-arid region, the research involved collecting medical history, anthropometric measurements, and blood samples to analyze glycemic and lipid profiles, along with C-reactive protein levels. We used an adapted the Molecular Degree of Perturbation model to analyze deviations in metabolic markers from a healthy control group. Statistical analyses included Mann-Whitney and Fisher exact tests, backward logistic regression, and hierarchical cluster analysis. The study identified a direct and independent association between elevated Metabolic Disturbance Degree and both overweight and obesity in children, with significant differences in CRP, Triglycerides, and HDL levels noted between obese and healthy-weight groups. The findings highlight the critical need for early detection and comprehensive understanding of obesity-related changes to mitigate the severe health risks associated with childhood obesity.

Moderate aerobic training counterbalances the deleterious effect of undernutrition on oxidative balance and mitochondrial markers.

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Candida spp. isolated from recreational coastal waters of Rio de Janeiro - Brazil: Focus on antifungal resistance and virulence attributes.

The use of recreational waters is a widespread activity worldwide, and one of the risks associated with this practice is the exposure of bathers to microorganisms that may arise due to pollution caused by inadequate infrastructure and sanitation. In the present work, we isolated Candida spp. (n = 24) from five recreational beaches in Rio de Janeiro, Brazil, in order to evaluate their susceptibility to antifungals, the production of virulence attributes and the in vivo virulence using Tenebrio molitor larvae as a model. The ITS1-5.8S-ITS2 gene sequencing identified thirteen isolates (54.1 %) as C. tropicalis, seven (29.1 %) as C. krusei (Pichia kudriavzevii), one (4.2 %) as C. rugosa (Diutina rugosa), one (4.2 %) as C. mesorugosa (Diutina mesorugosa), one (4.2 %) as C. utilis (Cyberlindnera jadinii) and one (4.2 %) as C. parapsilosis. C. tropicalis isolates showed resistance to azoles and susceptibility to amphotericin B, flucytosine and caspofungin. C. krusei isolates were resistant to fluconazole, caspofungin and itraconazole, with 42.8 % resistance to flucytosine, besides susceptibility to voriconazole and amphotericin B. The remaining species were susceptible to all tested antifungals. All Candida isolates adhered to abiotic surfaces and formed biofilm on polystyrene, albeit to varying degrees, and produced aspartic protease and hemolytic activity, which are considered fungal virulence attributes. C. tropicalis, C. krusei and C. utilis isolates produced phytase, while the only esterase producer was C. tropicalis. Regarding resistance to osmotic stress, all isolates of C. tropicalis, C. parapsilosis and C. mesorugosa grew up to 7.5 % NaCl; the remaining isolates grew up to 1.87-3.75 % NaCl. The mortality caused by fungal challenges in T. molitor larvae was variable, with C. tropicalis, C. utilis and C. parapsilosis being more virulent than C. krusei and C. rugosa complex. Collectively, the presence of these yeasts, particularly the virulent and resistant isolates, in recreational waters can pose a significant health risk to bathers.

Obstructive sleep apnea may induce sleep-wake cycle dysregulation: An actigraphic study.

Obstructive sleep apnea (OSA) causes sleep fragmentation and excessive daytime sleepiness (EDS). OSA has been hypothesised to impair the circadian sleep-wake rhythm, and this dysregulation may in turn exacerbate OSA-related diurnal symptoms. Hence, this study aimed to assess the sleep-wake rhythm through actigraphy, and its relationship with EDS in patients with untreated OSA. Patients with moderate-severe OSA (apnea-hypopnea index ≥15/h) and healthy controls (HC) underwent a 7-day actigraphic recording to evaluate the sleep-wake rhythm. Participants underwent a sleep medicine visit and completed the self-report questionnaires assessing EDS (Epworth sleepiness scale, ESS), sleep quality (Pittsburgh sleep quality index, PSQI), and chronotype (morningness-eveningness questionnaire, MEQ). This study included 48 OSA patients (72.9% males; mean age 56.48 ± 9.53 years), and 22 HC (45.5% males; mean age 53.73 ± 18.20 years). After controlling for MEQ scores, actigraphic recording showed that the OSA patients present a lower sleep time (p = 0.011) and sleep efficiency (p = 0.013), as well as a higher sleep latency (p = 0.047), and sleep fragmentation (p = 0.029) than the HC. Regarding the sleep-wake rhythm actigraphic parameters, the OSA patients showed a lower average activity during the most active 10-hour period (p = 0.036) and a lower day/night activity ratio (p = 0.007) than the HC. Patients with OSA also reported higher ESS (p = 0.005) and PSQI scores (p < 0.001), and a chronotype less of morning type (p = 0.027) than the HC. In conclusion, this study documented a reduced diurnal motor activity and lower day/night activity ratio in OSA patients than in controls. These findings suggest a dysregulation of the circadian sleep-wake rhythm in OSA, possibly related to both EDS and reduced daytime motor activity.

Children's satisfaction with nursing care during hospitalization: A cross-sectional study.

PURPOSE: To assess hospitalized children's satisfaction with nursing care. DESIGN AND METHODS: Cross-sectional study using the "Children Care Quality at Hospital" questionnaire. 61 children admitted to the Pediatrics Department of a hospital in the Northern Region of Portugal were enrolled. RESULTS: The ranged age of the participants was 6 to 15 (10,61 ± 2,66 years), and most were male (52.46%; n = 32). The mean score in the three domains was 128 (77.11%), reflecting children's high satisfaction with the nursing care provided during hospitalization. The domain most valued was Nurse Characteristics, while the least valued was Nursing Environment. CONCLUSION: Results provide essential input for the dimensions to be considered when planning nursing care for children, managing care, and the physical environment in the wards. IMPLICATIONS FOR PRACTICE: These results highlight the need to hear children's voices. This must encourage nurses to reflect on how children evaluate nursing care and, by doing so, to increase the quality of nursing care provided in Pediatrics settings.

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma.

BACKGROUND: Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation. OBJECTIVE: To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. METHODS: We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded. RESULTS: Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n = 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P = .03). CONCLUSIONS: Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

What are the main oral manifestations in heart transplant patients? A scoping review.

OBJECTIVE: The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT). MATERIAL AND METHODS: A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis. RESULTS: A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth. CONCLUSION: Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

Renoprotective mechanisms of exercise training against acute and chronic renal diseases - A perspective based on experimental studies.

Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.

Alteration of circadian sleep-wake rhythm and salivary melatonin secretion in idiopathic/isolated REM sleep behavior disorder: Preliminary evidence.

OBJECTIVE/BACKGROUND: Idiopathic/isolated REM sleep behavior disorder (iRBD) is widely regarded as an early sign of neurodegeneration leading to synucleinopathies. While circadian rhythm alterations in iRBD have been preliminarily demonstrated, evidence on melatonin secretion patterns in this clinical condition is limited. To address this knowledge gap, this exploratory study aimed to integrate salivary melatonin measurement with actigraphic monitoring in individuals with iRBD and age-matched healthy controls (HC) under real-life conditions. METHODS: Participants diagnosed with iRBD and HC underwent clinical evaluation and wore an actigraph for seven days and nights. Salivary melatonin concentrations were measured at five time points during the last night of recording. Comparative analyses were conducted on clinical data, actigraphic parameters, and melatonin levels between the two groups. RESULTS: iRBD participants (n = 18) showed greater motor (p < 0.01) and non-motor symptoms (p < 0.001), alongside disruptions in circadian sleep-wake rhythm compared to HC (n = 10). Specifically, actigraphy revealed a delayed central phase measurement (p < 0.05), reduced activity during the most active hours (p < 0.001), and decreased relative amplitude (p < 0.05). Total salivary melatonin concentration was significantly lower in iRBD (p < 0.05), with a slight but non-significant phase delay in dim light melatonin onset. CONCLUSIONS: This exploratory study highlights a dysregulation of circadian sleep-wake rhythm coupled with reduced melatonin secretion in iRBD. Future research could add to these preliminary findings to evaluate novel treatment approaches to regulate the sleep-wake cycle and elucidate the implications of circadian dysregulation in the conversion from iRBD to neurodegeneration.

Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Antifungal Susceptibility Assessment of Innovative and Non-Conventional Lime Mortars Incorporating Almond-Shell Powder Bio-Waste Subjected to Particle-Dispersion Technique.

A favorable environment for fungi colonization in building materials' surfaces can emerge when certain hygrothermal conditions occur. Thus, reducing fungal growth susceptibility is of major interest. Furthermore, if the integration of bio-wastes is performed in parallel with the development of innovative materials for this purpose, a more sustainable and environmentally friendly material can be obtained. In this study, the fungal susceptibility of lime mortars incorporating almond-shell powder (ASP) microparticles (2 and 4%, wt.-wt. in relation to the binder content) was evaluated. The particle-dispersion technique was employed to prepare the bio-waste introduced in the mixtures. The fungal susceptibility of ASP samples was compared with nanotitania (n-TiO2) with recognized antifungal properties. Mechanical strength, water absorption, and wettability tests were also performed for a better characterization of the composites. Although the addition of 2% ASP led to mechanical properties reduction, an increase in the compressive and flexural strength resulted for 4% of the ASP content. Difficulties in fungal growth were observed for the samples incorporating ASP. No fungal development was detected in the mortar with 2% of ASP, which may be correlated with an increase in the surface hydrophobic behavior. Furthermore, mortars with ASP revealed a reduction in water absorption by capillarity ability, especially with 4% content, suggesting changes in the microstructure and pore characteristics. The results also demonstrated that an improvement in the physical and mechanical properties of the lime mortars can be achieved when ASP microparticles are previously subjected to dispersion techniques.

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.