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  • 1
    Online Resource
    Online Resource
    Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 17 ( 2023-08-22), p. 5447-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 17 ( 2023-08-22), p. 5447-
    Abstract: Background: High total IgE levels are weak predictors of T2High and have been reported in nonallergic asthma. Therefore, the role of total serum IgE (IgE) in the T2High phenotype is still debated. Objective: This study investigated the reliability of stratifying asthmatics into IgEHigh and IgELow within the T2High and T2Low phenotypes. Methods: This cross-sectional single-center study investigated the association of clinical, functional, and bio-humoral parameters in a large asthmatic population stratified by IgE ≥ 100 kU/L, allergen sensitization, B-EOS ≥ 300/µL, and FENO ≥ 30 ppb. Results: Combining T2 biomarkers and IgE identifies (1) T2Low-IgELow (15.5%); (2) T2Low-IgEHigh (5.1%); (3) T2High-IgELow (33.6%); and T2High-IgEHigh (45.7%). T2Low-IgELow patients have more frequent cardiovascular and metabolic comorbidities, a higher prevalence of emphysema, and higher LAMA use than the two T2High subgroups. Higher exacerbation rates, rhinitis, and anxiety/depression syndrome characterize the T2Low-IgEHigh phenotype vs. the T2Low-IgELow phenotype. Within the T2High, low IgE was associated with female sex, obesity, and anxiety/depression. Conclusions: High IgE in T2Low patients is associated with a peculiar clinical phenotype, similar to T2High in terms of disease severity and nasal comorbidities, while retaining the T2Low features. IgE may represent an additional biomarker for clustering asthma in both T2High and T2Low phenotypes rather than a predictor of T2High asthma “per se”.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12175447
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    Bone Morphogenic Proteins and Their Antagonists in the Lower Airways of Stable COPD Patients
    MDPI AG ; 2023
    In:  Biology Vol. 12, No. 10 ( 2023-10-03), p. 1304-
    Details
    In: Biology, MDPI AG, Vol. 12, No. 10 ( 2023-10-03), p. 1304-
    Abstract: Background: Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs. Objective: To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD. Methods: We measured the expression and localization of BMPs and some relevant antagonists in bronchial biopsies of stable mild/moderate COPD (MCOPD) (n = 18), severe/very severe COPD (SCOPD) (n = 16), control smokers (CS) (n = 13), and control non-smokers (CNS) (n = 11), and in lung parenchyma of MCOPD (n = 9), CS (n = 11), and CNS (n = 9) using immunohistochemistry and transcriptome analysis, in vitro after the stimulation of the 16HBE cells. Results: In bronchial biopsies, BMP4 antagonists CRIM1 and chordin were increased in the bronchial epithelium and lamina propria of COPD patients. BMP4 expression was decreased in the bronchial epithelium of SCOPD and MCOPD compared to CNS. Lung transcriptomic data showed non-significant changes between groups. CRIM1 and chordin were significantly decreased in the alveolar macrophages and alveolar septa in COPD patients. External 16HBE treatment with BMP4 protein reduced the bronchial epithelial cell proliferation. Conclusions: These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative–reparative responses of the diseased bronchioles and lung parenchyma.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology12101304
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661517-4
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  • 3
    Online Resource
    Online Resource
    Clinical Characterization of the Frequent Exacerbator Phenotype in Asthma
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 7 ( 2020-07-14), p. 2226-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-07-14), p. 2226-
    Abstract: Background: Asthma exacerbation is episodic worsening of respiratory symptoms in conjunction with the deterioration of lung function, which may occur independently from the asthma severity hampering asthmatics’ quality of life. This study aimed to characterize the patient phenotype more prone to asthma exacerbation (oral corticosteroid burst ≥2 per year) to allow the proper identification of such patients. Methods: This real-life, observational, cross-sectional study evaluated 464 asthmatic patients stratified according to the asthma exacerbations experienced in the previous year. Clinical, functional, and blood parameters were retrieved from chart data and were representative of patients in stable conditions. Results: The frequent asthma exacerbator was more commonly female, suffered from chronic rhinosinusitis with nasal polyposis, had reduced lung function and peripheral oxygen saturation, and had increased daily activity limitations. These patients often had severe asthma and more frequently needed hospitalization in their lives. Furthermore, the frequent asthma exacerbator had higher concentrations of serum immunoglobulin E (IgE) and exhaled nitric oxide with cut-off risk values of 107.5 kU/L (OR = 4.1) and 43.35 ppb (OR = 3.8), respectively. Conclusions: This study illustrates the clinical features of the frequent asthma exacerbator phenotype. Nevertheless, serum IgE and exhaled nitric oxide could allow the identification of this phenotype and the establishment of an appropriate therapeutic approach.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9072226
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 4
    Online Resource
    Online Resource
    Benchmark of Intraoperative Activity in Cardiac Surgery: A Comparison between Pre- and Post-Operative Prognostic Models
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 11 ( 2022-06-06), p. 3231-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 11 ( 2022-06-06), p. 3231-
    Abstract: Objectives: Despite its large diffusion and improvements in safety, the risks of complications after cardiac surgery remain high. Published predictive perioperative scores (EUROSCORE, STS, ACEF) assess risk on preoperative data only, not accounting for the intraopertive period. We propose a double-fold model, including data collected before surgery and data collected at the end of surgery, to evaluate patient risk evolution over time and assess the direct contribution of surgery. Methods: A total of 15,882 cardiac surgery patients from a Margherita-Prosafe cohort study were included in the analysis. Probability of death was estimated using two logistic regression models (preoperative data only vs. post-operative data, also including information at discharge from the operatory theatre), testing calibration and discrimination of each model. Results: Pre-operative and post-operative models were built and demonstrate good discrimination and calibration with AUC = 0.81 and 0.87, respectively. Relative difference in pre- and post-operative mortality in separate centers ranged from −0.36 (95% CI: −0.44–−0.28) to 0.58 (95% CI: 0.46–0.71). The usefulness of this two-fold preoperative model to benchmark medical care in single hospital is exemplified in four cases. Conclusions: Predicted post-operative mortality differs from predicted pre-operative mortality, and the distance between the two models represent the impact of surgery on patient outcomes. A double-fold model can assess the impact of the intra-operative team and the evolution of patient risk over time, and benchmark different hospitals on patients subgroups to promote an improvement in medical care in each center.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11113231
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 5
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    Online Resource
    Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 12 ( 2022-12-12), p. 3229-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 12 ( 2022-12-12), p. 3229-
    Abstract: Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of pirfenidone and nintedanib with a prolonged follow-up. We retrospectively collected clinical status, adverse events (AEs), and treatment changes from IPF patients who had started an antifibrotic treatment at our centre from December 2011 to December 2020, including 192 patients treated with pirfenidone and 89 with nintedanib. The majority of patients in both groups experienced one or more AEs during the follow-up. A higher proportion of AEs in the nintedanib group were effectively treated with behavioural modifications or additional medications compared with the pirfenidone group (52.5% vs. 40.6%, p = 0.04). Overall, a difference in the impact of AEs due to nintedanib versus pirfenidone resulted in a lower permanent discontinuation of therapy (8.3% vs. 18.3%, p = 0.02), with the latter being associated with a higher risk of drug discontinuation at 48 months after initiation (OR = 2.52, p = 0.03). Our study confirms the safety profile of antifibrotic drugs in IPF but highlights that AEs due to nintedanib are usually easier to manage and lead to fewer cases of permanent discontinuation of therapy.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10123229
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 6
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    Online Resource
    Functional Characterization of p.(Arg160Gln) PCSK9 Variant Accidentally Found in a Hypercholesterolemic Subject
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 4 ( 2023-02-07), p. 3330-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 4 ( 2023-02-07), p. 3330-
    Abstract: Familial hypercholesterolaemia (FH) is an autosomal dominant dyslipidaemia, characterised by elevated LDL cholesterol (LDL-C) levels in the blood. Three main genes are involved in FH diagnosis: LDL receptor (LDLr), Apolipoprotein B (APOB) and Protein convertase subtilisin/kexin type 9 (PCSK9) with genetic mutations that led to reduced plasma LDL-C clearance. To date, several PCSK9 gain-of-function (GOF) variants causing FH have been described based on their increased ability to degrade LDLr. On the other hand, mutations that reduce the activity of PCSK9 on LDLr degradation have been described as loss-of-function (LOF) variants. It is therefore important to functionally characterise PCSK9 variants in order to support the genetic diagnosis of FH. The aim of this work is to functionally characterise the p.(Arg160Gln) PCSK9 variant found in a subject suspected to have FH. Different techniques have been combined to determine efficiency of the autocatalytic cleavage, protein expression, effect of the variant on LDLr activity and affinity of the PCSK9 variant for the LDLr. Expression and processing of the p.(Arg160Gln) variant had a result similar to that of WT PCSK9. The effect of p.(Arg160Gln) PCSK9 on LDLr activity is lower than WT PCSK9, with higher values of LDL internalisation (13%) and p.(Arg160Gln) PCSK9 affinity for the LDLr is lower than WT, EC50 8.6 ± 0.8 and 25.9 ± 0.7, respectively. The p.(Arg160Gln) PCSK9 variant is a LOF PCSK9 whose loss of activity is caused by a displacement of the PCSK9 P’ helix, which reduces the stability of the LDLr-PCSK9 complex.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24043330
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Can STEreotactic Body Radiation Therapy (SBRT) Improve the Prognosis of Unresectable Locally Advanced Pancreatic Cancer? Long-Term Clinical Outcomes, Toxicity and Prognostic Factors on 142 Patients (STEP Study)
    MDPI AG ; 2023
    In:  Current Oncology Vol. 30, No. 7 ( 2023-07-24), p. 7073-7088
    Details
    In: Current Oncology, MDPI AG, Vol. 30, No. 7 ( 2023-07-24), p. 7073-7088
    Abstract: Aim: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Methods: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. Results: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age 〈 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. Conclusion: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol30070513
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2270777-3
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  • 8
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    Online Resource
    Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 8 ( 2022-07-22), p. 5179-5194
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 8 ( 2022-07-22), p. 5179-5194
    Abstract: The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63–0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29080410
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 9
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    Effectiveness of a Multifaced Antibiotic Stewardship Program: A Pre-Post Study in Seven Italian ICUs
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 15 ( 2022-07-28), p. 4409-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 15 ( 2022-07-28), p. 4409-
    Abstract: Multidrug resistance has become a serious threat for health, particularly in hospital-acquired infections. To improve patients’ safety and outcomes while maintaining the efficacy of antimicrobials, complex interventions are needed involving infection control and appropriate pharmacological treatments in antibiotic stewardship programs. We conducted a multicenter pre-post study to assess the impact of a stewardship program in seven Italian intensive care units (ICUs). Each ICU was visited by a multidisciplinary team involving clinicians, microbiologists, pharmacologists, infectious disease specialists, and data scientists. Interventions were targeted according to the characteristics of each unit. The effect of the program was measured with a panel of indicators computed with data from the MargheritaTre electronic health record. The median duration of empirical therapy decreased from 5.6 to 4.6 days and the use of quinolones dropped from 15.3% to 6%, both p 〈 0.001. The proportion of multi-drug-resistant bacteria (MDR) in ICU-acquired infections fell from 57.7% to 48.8%. ICU mortality and length of stay remained unchanged, indicating that reducing antibiotic administration did not harm patients’ safety. This study shows that our stewardship program successfully improved the management of infections. This suggests that policy makers should tackle multidrug resistance with a multidisciplinary approach based on continuous monitoring and personalised interventions.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11154409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Thoracic UltrasONOgraphy Reporting: The TUONO Study
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 23 ( 2022-11-30), p. 7126-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 23 ( 2022-11-30), p. 7126-
    Abstract: Lung ultrasound (LUS) is a validated technique for the prompt diagnosis and bedside monitoring of critically ill patients due to its availability, safety profile, and cost-effectiveness. The aim of this work is to detect similarities and differences among LUS reports performed in ICUs and to provide a common ground for an integrated report form. We collected all LUS reports during an index week in 21 ICUs from the GiViTI network. First, we considered signs, chest areas, and terminology reported. Then, we compared different report structures and categorized them as structured reports (SRs), provided with a predefined model form, and free unstructured text reports (FTRs) that had no predetermined structure. We analyzed 171 reports from 21 ICUs, and 59 reports from 5 ICUs were structured. All the reports presented a qualitative description that mainly focused on the presence of B-lines, consolidations, and pleural effusion. Zones were defined in 66 reports (39%). In SRs, a complete examination of all the regions was more frequently achieved (96% vs. 74%), and a higher impact on therapeutic strategies was observed (17% vs. 6%). LUS reports vary significantly among different centers. Adopting an integrated SR seems to promote a systematic approach in scanning and reporting, with a potential impact on LUS clinical applications.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11237126
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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