Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps

BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation.ObjectiveTo assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence.MethodsClinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP.ResultsAmong the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01).ConclusionOur results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Insuline resistance and insuline sensibility in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA), also referred to as obstructive sleep apnea-hypopnea (OSAH), is a sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort. It is the most common type of sleep disordered breathing (SDB) and is characterized by recurrent episodes of upper airway collapse during sleep. These episodes are associated with recurrent oxyhemoglobin desaturations and arousals from sleep. Despite being a common disease, OSAS is underrecognized by most primary care physicians; an estimated 80% of Americans with OSAS are not diagnosed. Apnea may occur hundreds of times nightly, 1-2 times per minute, in patients with severe OSA, and it is often accompanied by wide swings in heart rate, a precipitous decrease in oxygen saturation, and brief electroencephalographic (EEG) arousals concomitant with loud breathing sounds as a bolus of air is exhaled when the airway reopens. The cardinal symptoms of sleep apnea include the "3 S s": S noring, S leepiness, and S ignificant-other report of sleep apnea episodes. Recent studies suggest that OSA increases the risk of developing insulin resistance and type 2 diabetes. The aim of the present study was to assess whether obstructive sleep apnea is a risk factor for insulin resistance, using surrogate estimates of insulin-mediated glucose uptake. We studied a population of 174 (122 males) subjects evaluated in our Sleep Lab for the suspect of OSA. All subjects underwent a standard nocturnal polysomnography (Compumedics S-Series). The HOMA index, an index of insulin resistance and the QUICKI index, an index of insulin sensitivity, were calculated from the values of fasting glucose and insulin obtained in the morning. The percentage of patients with iper-trigliceridemia was significantly higher in patients with OSAS than in controls (P <00.5) . Insulin resistance (HOMA > 2.4) was higher in OSAS patients than in controls (P < 00.5), as well as BMI values were higher in patients with OSAS than in controls (P < 00.5) . The results showed that the risk factors for insulin resistance (HOMA > 2:45 ) were predominantly the BMI (OR 2.4, 95 % CI 1.3-4.6 , P <0.001) , OSA (OR 4.0, 95 % CI 1.6 -9.7 , P <0.001) and hypertension (OR 2.3 , 95% CI 1.2-4.3 , P<0.001). Revealed no correlation with sex , age, hypercholesterolemia and ipertrigligeridemia . We did a multiple regression in which the OSAS (OR 2.7, 95 % CI 1.2-3.70 , P <0.05) and BMI (OR 2.3, 95% CI 0.29-2.70 , P <0.05), but not hypertension (OR 1.8, 95% CI 0.8-6.0, P <0.8) were independent risk factors for insulin resistance. From the correlation between insulin levels and OSAS we got a positive relationship between insulin and AHI (r = 0:32, P <0.001) and insulin levels and BMI (r = 0:43, P <0.001)

High Flow Nasal Therapy Use in Patients with Acute Exacerbation of COPD and Bronchiectasis: A Feasibility Study

The efficacy and feasibility of high flow nasal therapy (HFNT) use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and bronchiectasis is unknown. We performed a single-center, single-arm prospective observational study in patients with AECOPD, documented bronchiectasis, pH &gt;= 7.35, respiratory rate (RR) &gt;= 26 breaths/minute despite receiving maximal medical treatment and oxygen via face mask up to 10 L/m. Patients received HFNT (Airvo 2, Fisher &amp; Paykel) at a gas flow of 50 L/min and FIO2 adjusted to maintain SpO(2) &gt;= 92%. Dyspnea, rated by Borg scale, RR, arterial blood gases and mucus production (ranging from 1 to 3) were collected before and 1 h after starting HFNT and then every 24 h for 3 days. Tolerance was measured using a visual analogic scale (VAS). Fifteen patients were enrolled. After 24 h, patients showed a significant improvement in dyspnea score [Borg scale from 6.7 +/- 1.4 to 4.1 +/- 1.3 (p&lt;.001)]; RR decreased from 29.6 +/- 2.7 breaths/min to 23.2 +/- 2.9 breaths/min (p&lt;.001); pCO2 significantly decreased after 24 h [58.4 +/- 13 vs. 51.7 +/- 8.2 (p=.003)] while quantity of mucus production increased [(1.1 +/- 0,6 vs. 2.4 +/- 0.7, p&lt;.001)]. No patient received invasive or noninvasive mechanical ventilation. Overall VAS score for HFNT tolerance was 6.5. HFNT was effective in improving dyspnea score, decreasing RR, improving gas exchange, and increasing mucus production in patients with AECOPD and coexisting bronchiectasis. Moreover, no safety concerns on its use were detected. Nevertheless, due to the single-arm design, the effect of HFNT could not be isolated from standard pharmacological treatment due to the study design

L’alcoolizzazione nei tumori primitivi e secondari del fegato

Monduzzi Editor

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy

Background. The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. Patients and methods. Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. Results. In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p p p 1) (p p p < 0.05). Conclusion. The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment