Real-life Clinical Study Research Articles

Effects of Mepolizumab in the treatment of type 2 CRSwNP: a real-life clinical study.

Mepolizumab was recently approved for treating Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) unresponsive to standard treatment or recurring after endoscopic sinus surgery (ESS). To date, few studies have assessed Mepolizumab's efficacy in severe type-2 CRSwNP. Our study aimed to analyze sinonasal outcomes in type-2 CRSwNP patients treated with 100mg Mepolizumab administered subcutaneously every four weeks. We conducted a retrospective study of patients with severe, recalcitrant CRSwNP treated with Mepolizumab. Demographic and clinical characteristics were collected, including age, sex, and comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), and allergic rhinitis (AR), as well as the number of previous ESS procedures and the interval since the last one. Patients were evaluated at baseline and after one year for blood eosinophil count, nasal polyp score (NPS), modified Lund-Kennedy score (mLKS), olfactory function (using a VAS scale and a 16-item Sniffin' identification test), SNOT-22, and sinus opacification on CT scans. The need for rescue ESS or systemic corticosteroids (SCS), response to treatment, and side effects were also recorded. Data from 27 patients were collected. After one year, all scores showed significant improvement. NERD was the only factor associated with a less favorable improvement in olfactory function. There were no side effects reported, although 2 patients discontinued Mepolizumab as they were considered "non-responders." Mepolizumab is safe and effective in reducing the clinical, endoscopic, and radiological burden of disease, as well as in decreasing the need for salvage ESS or systemic steroids.

Role of NT-proBNP and lung ultrasound in diagnosing and classifying heart failure in a hospitalized oldest-old population: a cross-sectional study.

Diagnosing and classifying heart failure (HF) in the oldest-old patients has technical and interpretation issues, especially in the acute setting. We assessed the usefulness of both N-terminal pro-brain natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) for confirming HF diagnosis and predicting, among hospitalized HF patients, those with reduced ejection fraction (HFrEF). We performed a cross-sectional study on 148 consecutive patients aged ≥ 80 years admitted to our Internal Medicine and Geriatrics ward with at least one symptom/sign compatible with HF and NT-proBNP ≥ 125 pg/mL. We measured serum NT-proBNP levels and performed LUS and transthoracic echocardiography (TTE) on admission before diuretic therapy. We divided our cohort into three subgroups according to the left ventricular ejection fraction (LVEF): reduced (LVEF ≤ 40%), mildly-reduced (LVEF = 41-49%) and preserved (LVEF ≥ 50%). The mean age was 88±5 years. Male prevalence was 42%. Patients with HFrEF were 19%. Clinical features and laboratory parameters did not differ between the three subgroups, except for higher NT-proBNP in HFrEF patients, which also had a higher number of total B-lines and intercostal spaces of pleural effusion at LUS. Overall, NT-proBNP showed an inverse correlation with LVEF (r = -0.22, p = 0.007) and a direct correlation with age, total pulmonary B-lines, and intercostal spaces of pleural effusion. According to the ROCs, NT-proBNP levels, pulmonary B-lines and pleural effusion extension were poorly predictive for HFrEF. The best-performing cut-offs were 9531 pg/mL for NT-proBNP (SP 0.70, SE 0.50), 13 for total B-lines (SP 0.69, SE 0.85) and one intercostal space for pleural effusion (SP 0.55, SE 0.89). Patients with admission NT-proBNP ≥ 9531 pg/mL had a 2-fold higher risk for HFrEF (OR 2.5, 95% CI 1.3-4.9), while we did not find any association for total B-lines ≥ 13 or pleural effusion ≥ 1 intercostal space with HFrEF. A significant association with HFrEF emerged for the combination of NT-proBNP ≥ 9531 pg/mL, total B-lines ≥ 13 and intercostal spaces of pleural effusion ≥ 1 (adjusted OR 4.3, 95% CI 1.5-12.9). Although NT-proBNP and LUS help diagnose HF, their accuracy in discriminating HFrEF from non-HFrEF was poor in our real-life clinical study on oldest-old hospitalized patients, making the use of TTE still necessary to distinguish HF phenotypes in this peculiar setting. These data require confirmation in more extensive and longer prospective studies.

Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry.

The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n=8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

Five-year outcomes in patients with multivessel coronary artery disease undergoing surgery or percutaneous intervention

The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)—356 patients or percutaneous coronary intervention (PCI)—679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P < 0.01 and 26.8% vs. 12.6%, P < 0.01, respectively), while CABG-patients experienced stroke more often (7.3% vs. 3.1% for PCI, P < 0.01). In real-life practice with long-term follow-up, none of the two revascularization modalities implemented following HT decisions showed overwhelming superiority: occurrence of death and MI were similar, rates of RR favoured CABG, while incidence of strokes advocated PCI.

Potential synergistic antihyperglycemic effects of co-supplemental Amla and Olive extracts in hyperlipidemic adults with prediabetes and type 2 diabetes: results from a real-life clinical study.

Hyperglycemia and type 2 diabetes mellitus (T2DM) pose a significant risk for cardiovascular diseases and associated complications in individuals with hyperlipidemia. Statin therapy, effective in reducing cholesterol and cardiovascular risks, paradoxically increases incident T2DM risk due to its adverse impact on glucose homeostasis. Therefore, there is a pressing need for safe, and effective adjunctive or alternative therapies to manage hyperglycemia in hyperlipidemic individuals. There is growing body of pharmacological evidence suggesting that Amla and Olive extract supplementation can be beneficial in managing hyperglycemia in individuals with hyperlipidemia. The present study aimed to assess for the first time the potential synergistic antihyperglycemic effects of a daily co-supplementation of 1,000 mg Amla fruit and 50 mg Olive fruit standardized extracts (Cholesfytol NG®) over a 2-months period in hyperlipidemic adults with T2DM or prediabetes. This retrospective cross-sectional observational study analyzed treatment outcomes in 191 hyperlipidemic adults under the care of their physicians at 57 General Practitioner clinics in Belgium during real-life clinical practice between March 19, 2020, and January 31, 2022. These participants received Cholesfytol NG® as supplementary therapy to improve their metabolic health. The supplement was prescribed in an open-label, non-randomized manner, tailored to each participant's need. After 2-months of Cholesfytol NG® supplementation, participants showed significant reductions in glycemia levels: in the T2DM group, levels decreased by 42.7 ± 17.9 mg/dL (27.9%, p < 0.0001), and in the prediabetic group, by 2.26 ± 11.5 mg/dL (4.7%, p = 0.0020). Conversely, no significant change was observed in participants with normal baseline glycemia (1.55 ± 10.3 mg/dL, p = 0.088). Overall, glycemia levels decreased from 96.4 ± 18.2 mg/dL to 94.0 ± 13.5 mg/dL (mean decrease of 2.4 ± 14.5 mg/dL, p < 0.0001). The supplement was well tolerated and no side-effects, serious adverse events, or treatment-emergent effects were reported. The findings of this real-life clinical study highlight the potential synergistic antihyperglycemic effects of co-supplementation with Amla and Olive fruit extracts in managing hyperglycemia, particularly in individuals with hyperlipidemia. These results suggest that this botanical combination may help mitigate risks associated with hyperglycemia and cardiovascular disease in hyperlipidemic population. ClinicalTrials.gov, NCT06187298.

Brigatinib in patients with ALK‐positive anaplastic large cell lymphoma who have failed brentuximab vedotin

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) patients (pts) who have failed brentuximab vedotin (BV) have a poor prognosis with a median OS after BV failure of 2.9 months and 2-year OS of 27.1% (Chihara D, 2019). ALK-inhibitors have shown interesting results in relapsed ALK+ ALCL, but in these studies, most pts had not received prior BV, which does not correspond to current standards of treatment in adults. Furthermore, there are currently several ALK-inhibitors, but too few pts available to test them in this rare and difficult-to-treat population. It is therefore important to evaluate these ALK-inhibitors in preclinical studies, before selecting one for a clinical study. We carried out a preclinical study and then a real-life clinical study. We generated a patient-derived xenograft (PDX) model from a fresh lymph node biopsy of a 41-year-old man newly diagnosed with ALK+ ALCL. Our PDX closely mimicked the patient’s primary tumor, as assessed by pathology, FISH, TCR gene rearrangement, WES and RNA-seq. We used this model to assess 8 ALK-inhibitors (alectinib, brigatinib, ceritinib, crizotinib, ensartinib, entrectinib, lorlatinib, gilteritinib). We selected and recommended brigatinib for clinical off-label use based on our preclinical results and the safety profile in pts with ALK-positive non-small cell lung cancer (NSCLC). Between Jan 2020 and Oct 2022, 15 French adults who have failed BV started brigatinib. At brigatinib initiation, the median age was 35 y (19–73; 2 pts > 60 y), 8/15 were male, the median number of prior treatment lines was 2 (1–8), 4/15 (27%) had received prior crizotinib, including 3 crizotinib-resistant (crizo-R) and 1 crizotinib-sensitive (crizo-S) who relapsed after discontinuation of the drug. 4 pts had previously undergone stem cell transplantation (3 autoSCT, 1 alloSCT). ALCL was refractory to the last treatment in 10/15 pts. 10/11 pts had detectable ALK transcript in blood by RT-PCR. Pts received brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg), as recommended in ALK-positive NSCLC. The best ORR was 93% (14/15) with 73% (11/15) CR according to Lugano response criteria. 2 crizo-R and the crizo-S pts achieved CR, and 1 crizo-R pt reached PR. Time to achieve CR ranged from 8 to 325 days. 9 pts were monitored for ALK transcript in blood over time and kinetics correlated with response. 5 CR pts were bridged to alloSCT. There were 4 progressions/relapses after brigatinib initiation, all occurring within the first 6 months. After a median follow-up of 1.3 years, 1-year PFS and OS were 72% and 85%, respectively. There was no permanent discontinuation of brigatinib related to adverse event (AE), and 3 pts had dose reduction for moderate AE (1 dyspnea and 2 cramps), with complete resolution. Keywords: Aggressive T-cell non-Hodgkin lymphoma, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. D. Sibon Consultant or advisory role: Takeda, AbbVie, Janssen, Roche

Statin-Associated Muscle Symptoms: Clinical Index in a hypertensive population candidated to lipid-lowering therapy but not taking statins

Aim: Statin-associated muscle symptoms (SAMS) are claimed to be frequent in clinical practice. The SAMS-clinical index (SAMS-CI) assesses the likelihood that muscle symptoms are related to statin use. We evaluated the prevalence and characteristics of muscle symptoms in hypertensive patients eligible for statin therapy according to their individual cardiovascular risk. Methods: Observational study on 390 consecutive outpatients referred to our Centre. All patients were asked the following question: “Have you ever taken a drug/nutraceutical that you think gave you muscle symptoms?”. Patients who answered “yes” were evaluated with SAMS-CI. Results: Mean age: 60.5±13.5 years. Male prevalence: 53.8%. Patients who have ever taken a statin (“statin+” group): 250. Patients who have never taken a statin but have taken at least one other drug (“statin-” group): 140. Prevalence of muscle symptoms did not differ between the groups (p=0.217). Age and number of drugs taken were significantly associated with muscle symptoms at multivariate analysis. A not clinically significant higher SAMS-CI score emerged in the “statin+” group (p=0.004). Localization and pattern of muscle symptoms did not differ between the groups (p=0.170). Timing of muscle symptoms onset after starting the drug (p=0.036) and timing of symptom improvement after withdrawal (p=0.002) were associated with statin therapy. Conclusions: Prevalence of patient-reported muscle symptoms was not associated with statin therapy in our real life clinical study, confirming the growing evidence that subjective muscle-related symptoms are often misattributed to statins, while they may more likely be related to the nocebo/drucebo effect or other common undiagnosed conditions.

Effect of Teriparatide on Bone Mineral Density and Bone Markers in Real-Life: Argentine Experience.

To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions. As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6-12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR.

Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women.

Background and Aims: Cardiac natriuretic peptides (NPs) exert several metabolic effects, including some on lipid metabolism. Higher NPs levels are likely to be associated with a favorable lipid profile. In in vitro studies, NPs have been found to modulate low-density lipoprotein receptor (LDLR) trafficking by preventing proprotein convertase subtilisin/kexin type 9 (PCSK9) overexpression. The aim of our study is to investigate a possible association between plasma levels of PCSK9 and N-terminal pro B-type natriuretic peptide (NT-proBNP) in vivo. Methods: We performed a cross-sectional study on 160 consecutive older male and female patients hospitalized for medical conditions. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Fasting blood samples were collected after clinical stabilization of the acute illness, the day before discharge. Results: The mean age was 87.8 ± 6.4 years with a female prevalence (62.5%). The median NT-proBNP was 2340 (814–5397) pg/mL. The mean plasma PCSK9 was 275.2 ± 113.2 ng/mL. We found an inverse correlation between plasma PCSK9 and NT-proBNP (r = −0.280; p = 0.001). This association was confirmed after taking into account NT-proBNP tertiles (plasma PCSK9 levels: 317.4 ± 123.6 ng/mL in the first tertile, 283.3 ± 101.8 ng/mL in the second tertile, 231.3 ± 99.0 ng/mL in the third tertile, p = 0.001) and even after an adjustment for confounding factors (beta = −0.361, p = 0.001 for ln(NT-proBNP); beta = −0.330, p = 0.001 for NT-proBNP tertiles). The strength of the correlation between plasma PCSK9 and NT-proBNP was likely greater in patients affected by type 2 diabetes mellitus (r = −0.483; p = 0.006) and in male patients (r = −0.431, p = 0.001). Conclusion: The inverse association found between PCSK9 and NT-proBNP plasma levels in our real-life clinical study supports the hypothesis that NPs may play a role in cholesterol metabolism, possibly through an inhibitory action on circulating PCSK9 concentrations, thus increasing the availability of LDLR.

SAT374 - Two-year safety and efficacy of tenofovir alafenamide in chronic hepatitis B: a HEllenic multicenter ReAl-life CLInical Study (HERACLIS-TAF)

SAT374 - Two-year safety and efficacy of tenofovir alafenamide in chronic hepatitis B: a HEllenic multicenter ReAl-life CLInical Study (HERACLIS-TAF)

Biodiversity screening of gut microbiome during the allogeneic hematopoietic stem cell transplantation: data from the real-life clinical practice

Biodiversity of a gut microbiome has been shown as an important predictor of transplant-related outcomes and infections in allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center real-life clinical study and implemented a routine gut microbiome diversity monitoring across the course of allogeneic HSCT. Twelve patients (with ALL, AML, CML, biphenotypic leukemia and aplastic anemia) were enrolled in a stool samples collection protocol before the start of HSCT and during a 30-day post-transplant period. We have shown the feasibility of a gut microbiome monitoring in a real-life clinical setting and have proven that the alpha-biodiversity of the microbiome is significantly reduced with HSCT in comparison with the individual patient baseline level (Xdc 72.93; p < 0.001; multivariate Dirichlet analysis), what may be related to the antibiotic use and conditioning regimen. Overall, the gut microbiome biodiversity monitoring may be clinically used in a real-life HSCT setting to identify the high-risk groups for developing bloodstream infections and transplant-related negative outcomes.

Understanding cost-utility analysis studies in the trauma and orthopaedic surgery literature.

Cost-utility analysis (CUA) studies are becoming increasingly important due to the need to reduce healthcare spending, especially in the field of trauma and orthopaedics.There is an increasing need for trauma and orthopaedic surgeons to understand these economic evaluations to ensure informed cost-effective decisions can be made to benefit the patient and funding body.This review discusses the fundamental principles required to understand CUA studies in the literature, including a discussion of the different methods employed to assess the health outcomes associated with different management options and the various approaches used to calculate the costs involved.Different types of model design may be used to conduct a CUA which can be broadly categorized into real-life clinical studies and computer-simulated modelling. We discuss the main types of study designs used within each category. We also cover the different types of sensitivity analysis used to quantify uncertainty in these studies and the commonly employed instruments used to assess the quality of CUAs. Finally, we discuss some of the important limitations of CUAs that need to be considered.This review outlines the main concepts required to understand the CUA literature and provides a basic framework for their future conduct.Cite this article: EFORT Open Rev 2021;6:305-315. DOI: 10.1302/2058-5241.6.200115

A non-interventional switch study in adult patients with asthma or COPD on clinical effectiveness of salmeterol/fluticasone Easyhaler® in routine clinical practice.

Background:Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler.Methods:The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up.Results:A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was ‘very easy’ to teach the use of Easyhaler and the training took less than 5 minutes in most cases.Conclusion:The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life setting. The reviews of this paper are available via the supplemental material section.

The use of drones and a machine-learning model for recognition of simulated drowning victims—A feasibility study

BackgroundSubmersion time is a strong predictor for death in drowning, already 10 min after submersion, survival is poor. Traditional search efforts are time-consuming and demand a large number of rescuers and resources. We aim to investigate the feasibility and effectiveness of using drones combined with an online machine learning (ML) model for automated recognition of simulated drowning victims. MethodsThis feasibility study used photos taken by a drone hovering at 40 m altitude over an estimated 3000 m2 surf area with individuals simulating drowning. Photos from 2 ocean beaches in the south of Sweden were used to (a) train an online ML model (b) test the model for recognition of a drowning victim. ResultsThe model was tested for recognition on n = 100 photos with one victim and n = 100 photos with no victims. In drone photos containing one victim (n = 100) the ML model sensitivity for drowning victim recognition was 91% (95%CI 84.9%–96.2%) with a median probability score that the finding was human of 66% (IQR 52−71). In photos with no victim (n = 100) the ML model specificity was 90% (95%CI: 83.9%–95.6%). False positives were present in 17.5% of all n = 200 photos but could all be ruled out manually as false objects. ConclusionsThe use of a drone and a ML model was feasible and showed satisfying effectiveness in identifying a submerged static human simulating drowning in open water and favorable environmental conditions. The ML algorithm and methodology should be further optimized, again tested and validated in a real-life clinical study.

Real-life clinical study: 1-year of treatment with burosumab of children and adolescents affected with X-linked hypophosphatemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SAT427 - Real-world experience from tenofovir alafenamide use in chronic hepatitis B: an Hellenic multicenter real-life clinical study (HERACLIS-TAF)

SAT427 - Real-world experience from tenofovir alafenamide use in chronic hepatitis B: an Hellenic multicenter real-life clinical study (HERACLIS-TAF)

Effectiveness of omalizumab on patient reported outcomes, lung function, and inflammatory markers in severe allergic asthma

BackgroundOmalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE antibodies. Randomized clinical trials and real life clinical studies have already confirmed benefits, cost-effectiveness and applicability of the medication. MethodOur study retrospectively reports on the clinical outcomes and airway inflammation in 157 severe allergic asthmatics who were initiated with omalizumab between 2007 and 2019. ResultsAfter 4 months of therapy, 76% of the patients were judged to have benefited from omalizumab and were admitted to prolonged treatment. During follow-up, we observed an improvement in asthma control, quality of life and spirometric performance. There was also a sustained reduction in exacerbation rate over the years. As for T2 biomarkers, FeNO significantly decreased and, in a subgroup of patients who had repeated sputum inductions, there was also significant reduction in sputum eosinophils but no change in blood eosinophil count. Lastly, we found a correlation between high FeNO levels at baseline and reduction in ACQ scores at 1 year. ConclusionWe conclude that omalizumab shows effectiveness in severe allergic asthma in a real life setting, by reducing exacerbation rate, improving patient perspective outcomes and airway calibre, together with reducing type-2 airway inflammation.

Short Course of Systemic Corticosteroids in Wheezy Children: Still an Open Question

We performed a real-life clinical study to identify the main indications for the prescription of short-course treatment with systemic glucocorticosteroids (GCS) for steroid naive children with acute virus-induced wheezing as well as to analyze the influence of such treatment on patients' serum cortisol level, other blood tests results and the length of stay in the hospital. The data of 44 patients who had acute wheezing, had no bacterial infection and were otherwise healthy were analyzed: 26 children received treatment with GCS and 18 children did not. Full blood count, biochemistry tests (Na, K, glucose) and blood cortisol levels of all patients were analyzed during treatment. The main indications for the short-term administration of systemic GCS were increased work of breathing, recurrent wheezing, clinical signs of atopy and a family history of asthma. Systemic GCS increased a sodium concentration (p = 0.014), decreased a cortisol level (p = 0.038), leukocyte (p = 0.043), neutrophil (p = 0.045), and eosinophil (p < 0.001) count in blood serum. The major reduction in the eosinophil count was observed in allergic children (p = 0.023). Older age was a risk factor for cortisol suppression (p = 0.018). The average length of stay in the hospital was longer in the intervention group (p = 0.039). Even short-course treatment with systemic GCS decreases the serum cortisol level and has a significant effect on other blood tests results. Systemic GCS used for acute virus-induced wheezing treatment did not prove to reduce the average length of stay in the hospital. Objective criteria for initiation of such treatment are still lacking, which might consequently lead to the overuse of corticosteroids.

Long-term evaluation of response to omalizumab therapy in real life by a novel multimodular approach: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study

BackgroundThe evidence on long-term real-life response measures to omalizumab therapy in moderate to severe asthma is limited. A universal assessment tool is needed to adequately evaluate response to omalizumab in these patients. ObjectiveTo design a multimodular response assessment tool and use it to measure and define response to omalizumab therapy in real-world settings. MethodsThe Real-life Effectiveness of Omalizumab Therapy (REALITY) study is a retrospective, long-term, real-life clinical study that evaluates response in individuals with allergic asthma who received omalizumab between 2004 and 2011. The Standardized Measure to Assess Response to Therapy (SMART) tool was designed to define response (1 year before to after treatment) by 3 modules: (1) physician's subjective assessment of asthma symptoms and control; (2) objective assessment of 6 parameters: improvement by 50% or more for asthma exacerbation, steroid bursts, emergency department visits, and hospitalizations; increase in forced expiratory volume in 1 second of 200 mL or greater; and improved Asthma Control Test score of 3 or higher; –and (3) true responders (patient meeting both module 1 and 2 criteria). Response was assessed and compared for 3 modules at desired time points. ResultsA total of 198 patients (mean age, 31.7 years [range, 3-77 years]; 98 [49%] female; mean omalizumab therapy duration, 2.49 years [range, 3 months to 8 years]; mean omalizumab dosage, 473 mg every 4 weeks; median baseline IgE level, 433 IU/mL) were included in this analysis. Overall visit adherence was 78%, although the adherence rate decreased annually by 20%. Response rates assessed by SMART modules were 61.3%, 60.8%, and 41.8% at 16 weeks, 84.8%, 72.2%, and 64.6% at 1 year, 82.4%, 71.2%, and 63.2% at 2 years, and 95.1%, 87.8%, and 85.4% at 5 years for modules 1, 2, and 3, respectively. There were no significant adverse reactions. ConclusionThe REALITY study has demonstrated long-term effectiveness of omalizumab therapy in individuals with allergic asthma in real-life settings. The SMART tool is promising as a potential standard assessment tool to measure and define response to asthma therapy. Trial RegistrationClinicalTrials.gov Identifier: NCT01776177.

CIRCULATING LOW-DENSITY LIPOPROTEIN CHOLESTEROL IS INVERSELY CORRELATED WITH N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE IN VERY ELDERLY HOSPITALIZED PATIENTS

Objective: Our studies on human adipocytes suggest that natriuretic peptides (NP) may affect plasma cholesterol levels by inhibiting PCSK9 expression, a key regulator of low-density lipoprotein receptor (LDLR). To test this hypothesis in a real-life clinical setting, we evaluated associations between NT-proBNP and cholesterol in very elderly hospitalized patients. Design and method: Cross sectional study on 288 very elderly admitted to our Internal Medicine and Geriatrics Department for medical conditions. NT-proBNP, total cholesterol (TC), HDL cholesterol (HDL-c) and triglycerides (TG) were collected after stabilization of the acute illness. Patients were taking no lipid-lowering drugs. Calculated LDL-cholesterol (cLDL) was used for the analyses. NT-proBNP was analyzed both as a continuous and as a discrete variable (NT-proBNP tertiles). Results: Mean age was 87.7 ± 6.2 years with female prevalence (57.3%). Median NT-proBNP: 2949 (1005–7335) pg/ml; mean TC: 145.1 ± 40.3 mg/dl; mean HDL-c: 38.4 ± 18.6 mg/dl; median TG: 100 (75–129) mg/dl; mean cLDL: 84.0 ± 29.5 mg/dl. We found a negative correlation between NT-proBNP and both TC and cLDL (ρ = −0.157; p = 0.008 and ρ = −0.166; p = 0.005, respectively), while no correlations emerged between NT-proBNP and HDL (ρ = −0.065; p = 0.275) or triglycerides (ρ = −0.009; p = 0.874). These associations were also confirmed for NT-proBNP tertiles (Figure 1). The inverse association between NT-proBNP and cLDL was maintained even after adjusting for sex, albumin, hemoglobin and cognitive impairment. Conclusions: We found an inverse association between NT-proBNP and LDL cholesterol levels, that remained statistically significant even after adjusting for covariates such as albumin, a common indicator of malnutrition or hepatic failure. Our real-life clinical study supports the possible direct role of NP on cholesterol metabolism, as suggested by our laboratory studies.