Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma.

Background: The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis. Objectives and methods: The present real-life study aimed to evaluate, in 22 allergic patients with severe eosinophilic asthma, the effects of benralizumab on asthma exacerbations and lung hyperinflation. Results: In this regard here we show that, after 24 weeks of add-on treatment, benralizumab completely depleted peripheral blood eosinophils (from 810 to 0 cells/μL; p < 0.0001), and significantly decreased both asthma exacerbation number (from 4 to 0; p < 0.0001) and residual volume (from 2720 to 2300 mL; p < 0.01). Moreover, at the same time point (24 weeks) benralizumab also increased pre-bronchodilator FEV1 (from 1295 to 1985 mL; p < 0.0001), FVC (from 2390 to 2974 mL; p < 0.0001), FEF25−75 (from 0.6 to 1.42 L/sec; p < 0.0001), IC (from 1940 to 2460 mL; not significant), and ACT score (from 14.73 to 22.95; p < 0.0001), as well as reduced prednisone intake (from 25 to 0 mg; p < 0.0001). Conclusion: In conclusion, our results suggest that via its anti-eosinophil actions benralizumab improved airflow limitation, lung hyperinflation, and respiratory symptoms, as well as lowered asthma exacerbation rate and abrogated OCS consumption in most patients

Novel Biological Therapies for Severe Asthma Endotypes

Severe asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research

Speech outcome in tongue cancer surgery: objective evaluation by acoustic analysis software

BACKGROUND. Cancer of the oral cavity is one of the most common malignancies of which 60% affect the tongue. Carcinoma of the tongue causes significant alterations of the articulatory and swallowing functions. The gold standard of care remains primary surgical resection with or without postoperative adjuvant therapy. Whereas T1 and T2 tongue tumors can be treated with more conservative surgeries, as partial glossectomies, the larger tumors require total and aggressive glossectomies which increase survival, but, on the other hand, they might often make speech, chewing and swallowing impossible. MATERIAL AND METHODS. Our study was performed on a total of 21 patients with Squamous Cell Carcinoma of the tongue who underwent either partial resection or hemiglossectomy. Each subject (either surgical patients or controls) was asked to pronounce the vowels /a/, /e/, /i/, /u/, and all signals were evaluated separately by two operators. Acoustic (F0, jitter, shimmer, NHR) and vowel metric (the ratio F2i/F2u, tVSA, qVSA, FCR) features have been extracted. In order to define the speech intelligibility, all patients were evaluated by two doctors and one speech therapist and all patients received the Speech Handicap Index (SHI) translated into Italian language before recording. RESULTS. No statistically significant variations were observed, regardless of the gender, between controls and surgically resected patients when tumor staging was T1-T2. On the contrary, when patients had to undergo more extensive surgical resection due to the presence of a T3-T4 tumor, a dramatic increase of F2u could be observed. This change, together with a decrease of F2i, led to a highly significant reduction in the F2i/F2u parameter in surgically resected patients as compared to controls. The other parameters which were reduced in a statistically significant manner in T3-T4 surgically resected patients were tVSA and qVSA. Instead, two parameters increased in a statistically significant manner in T3-T4 surgically resected patients: FCR and SHI. Again, none of the above-mentioned parameters was altered in a statistically significant manner in early tumor stage resected patients, regar dless of the gender. CONCLUSION. For the first time, we used a series of newly developed formant parameters, introduced by various authors for the study of the articulatory undershoot of the tongue in various neurodegenerative diseases. The statistical analysis of our results highlighted in an incontrovertible way a strong correlation and significance of each of our parameters F2 / i / / F2 / u /, FCR, tVSA, qVSA, with the entity of the TNM, and therefore of the surgical extension of the resection, and in parallel with the loss of the intelligibility of the speech that proportionally reaches higher values in the advanced stages of the disease as can be deduced from the SHI trend

Indacaterol/glycopyrronium/mometasone fixed dose combination for uncontrolled asthma

Introduction: Asthma symptoms can be relieved through a maintenance treatment combining long-acting β2-agonist and inhaled corticosteroids (LABA/ICS). However, for patients with inadequately controlled asthma, the LABA/ICS combination might not be sufficient, and clinical guidelines recommend the administration of inhaled long-acting muscarinic antagonists (LAMA) as an add-on therapy to better control asthma and improve lung function. For nearly two decades, the only LAMA to be approved on the market has been tiotropium. Areas covered: We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching the PubMed database. Molecular mechanisms and clinical data support the use of a once-daily, single-inhaler fixed dose combination of the LABA/LAMA/ICS indacaterol/glycopyrronium/mometasone (IND/GLY/MF), the first therapy combining three agents in a fixed dose approved in Europe for the treatment of uncontrolled asthma. Expert opinion: IND/GLY/MF was superior to both IND/MF and salmeterol/fluticasone, a well-established LABA/ICS combination improving the lung function in uncontrolled asthma. Moreover, IND/GLY/MF, delivered through the Breezhaler inhaler in a single inhalation, is the first inhaled therapy prescribed alongside a digital companion, a sensor and the Propeller app, allowing for improved treatment adherence, reduced rescue inhaler usage and hospitalizations, increased patient satisfaction and asthma control

Sirtuin 1 and Aging Theory for Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed

S. aureus and IgE-mediated diseases: pilot or copilot? A narrative review

Introduction: S. aureus is a major opportunistic pathogen that has been implicated in the pathogenesis of several chronic inflammatory diseases including bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), chronic spontaneous urticaria (CSU), and atopic dermatitis. S. aureus can induce the production of both polyclonal and specific IgE that can elicit an inflammatory cascade. Areas covered: The link between the sensitization to S. aureus enterotoxins and the severity of several chronic inflammatory diseases is reviewed in detail, as well as its therapeutic implications. Expert opinion: An anti-IgE strategy to inhibit S. aureus enterotoxins would be a valid approach to treat several endotypes of severe asthma, CRSwNP and CSU in which IgE against S. aureus enterotoxins should represent, not only a marker of severity of the diseases but also a target of a treatment

Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies

none8noSeveral reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor.Damiani, Elisa; Donati, Abele; Serafini, Giulia; Rinaldi, Laura; Adrario, Erica; Pelaia, Paolo; Busani, Stefano; Girardis, MassimoDamiani, Elisa; Donati, Abele; Serafini, Giulia; Rinaldi, Laura; Adrario, Erica; Pelaia, Paolo; Busani, Stefano; Girardis, Massim