Incidence and risk factors of hospitalization for bronchiolitis in preterm children: a retrospective longitudinal study in Italy

<p>Abstract</p> <p>Background</p> <p>Bronchiolitis is a distressing, potentially life-threatening respiratory condition that affects infants. We evaluated the incidence and risk factors of hospitalization for broncholitis in preterm infants (i.e., a gestational age of <36 weeks) born between 2000 and 2006, and the use and impact of Palivizumab, a monoclonal antibody that in randomized clinical trials has been shown to lessen the severity of RSV-related bronchiolitis.</p> <p>Methods</p> <p>Retrospective cohort study that linked data from four health administrative databases in the Lazio region (a region of central Italy): the birth register, the hospital discharge register, and two ad-hoc databases that record the doses of Palivizumab administered at two local health units.</p> <p>Results</p> <p>Among 2407 preterm infants, 137 had at least one hospitalization for bronchiolitis in the first 18 months of life, an overall incidence rate of 4.70 per 100 person-years (95%CI: 3.98-5.56); similar incidence rates were observed by calendar year. A multiple Poisson model showed that the following characteristics were associated with higher incidence: younger age of the infant, the period between October-April, male gender, low Apgar score at birth, low birth weight, and low maternal educational level. At least one dose of Palivizumab was administered to 324 (13.5%) children; a dramatic increase from 2000 (2.8%) to 2006 (19.1%) (p < 0.01) was observed. Other factors independently associated with more frequent Palivizumab use were older maternal age, Italian-born mothers, female gender, low Apgar score, low birth weight, shorter gestational age, a diagnosis of broncho-dysplasia, and the month of birth. It is of note that none of the 34 children with congenital heart disease were prescribed Palivizumab. Performing several multiple Poisson models that also considered Palivizumab use as covariate, although the point estimates were in agreement with previous clinical trial results, we did not find in most of them a significant reduction for immunized children to be hospitalized for bronchiolitis.</p> <p>Conclusion</p> <p>In Italy the incidence of hospitalization for bronchiolitis, and its associated risk factors, are similar to that found in other countries. Although Palivizumab use is associated with the most important characteristics of severe prematurity, other aspects of its non-use in children with congenital heart disease, the age and the birth country of the mother suggest the need for public health measures that can reduce these health disparities. Finally, the estimated effectiveness of Palivizumab in routine practice, although not significant, confirms the results of previous clinical trials, but its impact on modifying the temporal trend in this population is still negligible.</p

Interaction of the Transcription Start Site Core Region and Transcription Factor YY1 Determine Ascorbate Transporter SVCT2 Exon 1a Promoter Activity

Transcription of the ascorbate transporter, SVCT2, is driven by two distinct promoters in exon 1 of the transporter sequence. The exon 1a promoter lacks a classical transcription start site and little is known about regulation of promoter activity in the transcription start site core (TSSC) region. Here we present evidence that the TSSC binds the multifunctional initiator-binding protein YY1. Electrophoresis shift assays using YY1 antibody showed that YY1 is present as one of two major complexes that specifically bind to the TSSC. The other complex contains the transcription factor NF-Y. Mutations in the TSSC that decreased YY1 binding also impaired the exon 1a promoter activity despite the presence of an upstream activating NF-Y/USF complex, suggesting that YY1 is involved in the regulation of the exon 1a transcription. Furthermore, YY1 interaction with NF-Y and/or USF synergistically enhanced the exon 1a promoter activity in transient transfections and co-activator p300 enhanced their synergistic activation. We propose that the TSSC plays a vital role in the exon 1a transcription and that this function is partially carried out by the transcription factor YY1. Moreover, co-activator p300 might be able to synergistically enhance the TSSC function via a “bridge” mechanism with upstream sequences

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p&lt;0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p&lt;0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p&lt;0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p&lt;0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Selenium is effective in inducing lymphocyte progression through cell cycle in cancer patients: potential mechanisms for its activity

Epidemiologic evidence in humans suggests a role for selenium in reducing cancer incidence and mortality. The aim of the present study was that to assess the ability of selenium dioxide (SeO2) to enhance the lymphocyte progression through the cell cycle in patients with advanced (stage IV) cancer. Ten patients (mean age 51.9 years, range: 32-74; M/F ratio: 3/7) with tumors at different sites were included in the study. The addition into culture of SeO2 1.5 μM enhanced significantly the progression into S phase of PBMCs isolated from cancer patients, whilst no significant effect was observed on PBMCs isolated from controls. ROS levels were significantly higher, whereas GPx activity was significantly lower in cancer patients than controls. Serum levels of IL-6 and TNFα were significantly higher in cancer patients than controls. Our results show the ability of selenium to induce a progression of PBMCs from cancer patients into the cell cycle, which is an essential prerequisite for the physiological functioning of the immune system and thus positively influence the immune status of advanced cancer patients. The mechanism of action of selenium could be to downregulate the production and release of proinflammatory cytokines, which have a role in cancer progression and particularly in the onset of cachexia