Background:
The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal ...sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients.
Methods:
The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS).
Results:
Patients who received a first-line pertuzumab-based regimen showed better PFS (p < 0.0001) and OS (p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine (p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine (p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 (p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era. No significant differences emerged when comparing patients treated with ‘old’ or ‘new’ drugs (p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account.
Conclusion:
Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.
Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that ...could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1.
We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above.
Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels.
These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.
Asthma control is the goal of asthma management. A nationwide study on this aspect was launched by the Italian Society of Paediatric Allergy and Immunology (ControL'Asma study).
To define variables ...associated with different asthma control grades in a nationwide population of asthmatic children and adolescents.
This cross-sectional real-world study included 480 asthmatic children and adolescents (333 males, median age 11.2 years) consecutively enrolled in 10 third level pediatric allergy clinics. According to the Global Initiative for Asthma (GINA) document, history, medication use, perception of asthma symptoms assessed by visual analog scale (VAS), clinical examination, lung function, childhood asthma control test (cACT)/asthma control test (ACT), and asthma control level were evaluated.
Considering GINA criteria, asthma was well controlled in 55% of patients, partly controlled in 32.4%, and uncontrolled in 12.6%. Regarding cACT/ACT, asthma was uncontrolled in 23.2%. Patients with uncontrolled asthma had the lowest lung function parameters and VAS scores, more frequent bronchial obstruction and reversibility, and used more oral and inhaled corticosteroids (CS).
The ControL'Asma study, performed in a real-world setting, showed that asthma in Italian children and adolescents was usually more frequent in males. Asthmatic patients had an early onset and allergic phenotype with very frequent rhinitis comorbidity. Uncontrolled and partly controlled asthma affected about half of the subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in asthma management.
According to the World Health Organization (WHO), the worldwide obesity rate has tripled since 1975. In Europe, more than half of the population is overweight and obese. Around 2.8 million people die ...each year worldwide as a result of conditions linked to being overweight or obese. This study aimed to analyze the policies, approaches, and solutions that address the social and health unmet needs of obese patients, at different levels, in order to simulate the definition of an integrated approach, and to provide and share examples of innovative solutions supporting health promotion, disease prevention, and integration of services to improve the collaboration between the different health and care stakeholders involved across the country and in the lives of obese patients. A collaborative approach involving various levels of government and regional experts from different European countries was applied to identify, explore, and evaluate different aspects of the topic, from the innovation perspective and focusing on a European and a regional vision. Currently, people prefer more foods rich in fats, sugars, and salt/sodium than fruits, vegetables, and fiber. This behavior leads to a significant negative impact on their health-related quality of life. Changes in healthcare systems, healthy policy, and approaches to patient care and better implementation of the different prevention strategies between all the stakeholders are needed, taking advantage of the digital transformation of health and care. Such changes can support obese patients in their fight against an unhealthy lifestyle and at the same time reduce healthcare costs.
Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this ...real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.
All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.
Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.
Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.
Aim/Hypothesis
To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.
...Methods
Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019.
Results
Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively).
Conclusions/Interpretation
There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.
The production of Klebsiella pneumoniae carbapenemases (KPCs) by Enterobacteriaceae has become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing ...K. pneumoniae (KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-control study in five large Italian hospitals. The case cohort consisted of adult inpatients whose hospital stay included at least one documented isolation of a KPCKP strain from a clinical specimen. For each case enrolled, we randomly selected two matched controls with no KPCKP-positive cultures of any type during their hospitalization. Matching involved hospital, ward, and month/year of admission, as well as time at risk for KPCKP isolation. A subgroup analysis was also carried out to identify risk factors specifically associated with true KPCKP infection. During the study period, KPCKP was isolated from clinical samples of 657 patients; 426 of these cases appeared to be true infections. Independent predictors of KPCKP isolation were recent admission to an intensive care unit (ICU), indwelling urinary catheter, central venous catheter (CVC), and/or surgical drain, ≥ 2 recent hospitalizations, hematological cancer, and recent fluoroquinolone and/or carbapenem therapy. A Charlson index of ≥ 3, indwelling CVC, recent surgery, neutropenia, ≥ 2 recent hospitalizations, and recent fluoroquinolone and/or carbapenem therapy were independent risk factors for KPCKP infection. Models developed to predict KPCKP isolation and KPCKP infection displayed good predictive power, with the areas under the receiver-operating characteristic curves of 0.82 (95% confidence interval CI, 0.80 to 0.84) and 0.82 (95% CI, 0.80 to 0.85), respectively. This study provides novel information which might be useful for the clinical management of patients harboring KPCKP and for controlling the spread of this organism.
Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS‐CoV‐2 in hematological patients compared to different control populations. Two ...independent reviewers screened the literature assessing clinical outcomes of SARS‐CoV‐2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID‐19 related mortality, secondary outcomes were hospital and intensive‐care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID‐19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID‐19 related mortality (OR, 2.12; 95% CI, 1.77–2.54), hospitalization (OR, 1.98; 95% CI, 1.15–3.43), intensive‐care admission (OR, 1.77; 95% CI, 1.38–2.26), and MV (OR, 2.17; 95% CI, 1.71–2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta‐regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID‐19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID‐19 clinical progression compared to both the general population and to patients with solid cancer.
Abstract
Background
The aim of this study was to describe the long-term evolution of post-COVID-19 syndrome over 2 years after the onset of severe acute respiratory syndrome coronavirus type 2 ...(SARS-CoV-2) in survivors of the first wave.
Methods
This prospective study was based on interviews and investigated post-COVID-19 syndrome 6, 12, and 24 months after the disease onset in all adult in- and outpatients with COVID-19 followed at Udine Hospital (Italy) during the first wave (March–May 2020). Humoral response, vaccination status, and reinfection were assessed.
Results
Overall, 230 patients (53.5% female; mean age 54.7 years) were interviewed 2.3 years (standard deviation = 0.11) after acute onset. Post-COVID-19 syndrome was observed in 36.1% of patients (n = 83) at 2 years. The most common persistent symptoms were fatigue (14.4%), rheumatological (14.4%), and psychiatric symptoms (9.6%). Overall, 55.4% (46 of 83) of long haulers searched for healthcare system support and 21 (45.7%) were visited by a specialist. Female gender (odds ratio OR = 2.50, P = .005), a proportional increase in the number of symptoms during acute COVID-19 (OR = 1.40, P = .001), and the presence of comorbidities (OR = 1.57, P = .004) were all independent risk factors for post-COVID-19 syndrome. Vaccination and reinfection had no impact on post-COVID-19 syndrome dynamics. The presence of receptor-binding domain (RBD) SARS-CoV-2 immunoglobulin G (IgG) and non-RBD SARS-CoV-2 IgG titers were not associated with the occurrence of post-COVID-19 syndrome.
Conclusions
Two years after COVID-19, the burden of persistent symptoms remains high among in- and outpatients’ population infected during the first wave. Post-COVID-19 dynamic does not seem to be influenced by SARS-CoV-2 immunization status and reinfection.
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