Bentonbeasley1837

Screening for de novo donor-specific HLA antibodies (DSAs) after kidney transplantation is widely recommended. The aim of this single-center, cross-sectional study was to investigate the frequency of therapeutic interventions triggered by de novo DSA screening. We included 464 patients screened for de novo DSA at annual visits after a median of 5 years post-transplant (range 1 to 19 years). Overall, de novo DSAs were detected in 55/464 patients (11.9%) with a stepwise increase of the prevalence from 4.9% at 1 year post-transplant to 18.9% at >10 years post-transplant. Subsequent allograft biopsies were performed in 24/55 patients (44%). The main reasons to omit biopsies were good/stable allograft function and anticipated lack of clinical consequences (eg, relevant comorbidities). Rejection processes were detected in 16/24 biopsies (67%). Therapeutic interventions were made in 18/464 screened patients (3.9%) with a significantly higher rate in the youngest quartile of patients (≤48 years; 7.9%) compared to the middle 50% (49-67 years; 3%) and the oldest quartile (≥68 years; 1.7%) (P = .03). Our study suggests that the frequency of therapeutic interventions triggered by de novo DSA screening after kidney transplantation is overall low, but significantly higher in younger patients, arguing for a personalized, age-adapted de novo DSA screening strategy.An underlying cause of breast cancers has been largely attributed to defects in the DNA damage response (DDR) pathway. In particular, the homologous recombination (HR) pathway repairs double-stranded breaks (DSBs) in DNA, ultimately protecting the cell from genomic instability and thus preventing the accumulation of transforming mutations. In line with this, mutations in a number of genes encoding HR proteins are a well-studied cause of HR deficiency (HRD), and, at the germline level, can confer risk to breast cancer but also occur somatically, contributing to sporadic breast cancer development, progression and response to therapy. Our understanding of the biological processes involved in HR and how these become compromised during breast cancer development has led to a better understanding of how HRD cells can be targeted with specific DNA damaging agents and/or with synthetic lethal targeting approaches such as PARP inhibition. Additionally, in vitro and preclinical modeling has supported the development of clinical trials to assess targeted therapies such as PARP inhibitors (PARPis), ultimately leading to development of therapies with greater clinical benefit. A number of challenges have been encountered, including resistance to therapy; however, addressing these challenges head-on and continually driving scientific research and clinical trials with innovative therapies will contribute to our ability to target HRD in breast cancers. Ongoing research efforts into HRD in breast cancer development are therefore essential, even in the era of targeted therapies, to provide innovative strategies for improved tumor responses.Antihistamine use for primary treatment of atopic dermatitis (AD) is not recommended, but current guidelines state that sedating antihistamines are favored over non-sedating antihistamines for relief of burdensome pruritus. We analyzed the National Ambulatory Medical Care Survey data to compare use of antihistamines between dermatologists and non-dermatologists. Overall, dermatologists are more likely to prescribe sedating than non-sedating antihistamines when compared to non-dermatologists (P less then .001, δabs = 0.45). Patients under 21 years old (P = .03, δabs = 0.10) and Black patients (P less then .001, δabs = 0.19) were also more likely to receive sedating antihistamines than non-sedating antihistamines. These findings highlight the differential prescribing practices for atopic dermatitis among physicians.Non-bilayer phospholipids arrangements (NPAs) are transient molecular associations different from lipid bilayers. learn more When they become stable, they can trigger a disease in mice resembling human lupus, which is mainly characterized by the production of anti-NPA IgG antibodies. NPAs are stabilized on liposomes or cell bilayers by the drugs procainamide or chlorpromazine, which produce drug-induced lupus in humans. Here, we evaluated the participation of the TH 2 response, through its hallmark cytokine IL-4, on the development of the lupus-like disease in mice. Wild-type or IL-4 knockout BALB/c mice received liposomes bearing drug-induced NPAs, the drugs alone, or an anti-NPA monoclonal antibody (H308) to induce the lupus-like disease (the last two procedures stabilize NPAs on mice cells). IL-4 KO mice showed minor disease manifestations, compared to wild-type mice, with decreased production of anti-NPA IgG antibodies, no anti-cardiolipin, anti-histones and anticoagulant antibodies, and no kidney or skin lesions. In these mice, H308 was the only inducer of anti-NPA IgG antibodies. These findings indicate that IL-4 has a central role in the development of the murine lupus-like disease induced by NPA stabilization.Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.