Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients.

Purpose: The aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients.

Methods: A total of 195 eligible early BC cases were tested for genomic risk between 2006 and 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics.

Recent Insights into Endogenous Mammalian Cardiac Regeneration Post-Myocardial Infarction.

Myocardial infarction (MI) is a critical global health issue and a leading cause of heart failure. Indeed, while neonatal mammals can regenerate cardiac tissue mainly through cardiomyocyte proliferation, this ability is lost shortly after birth, resulting in the adult heart's inability to regenerate after injury effectively. In adult mammals, the adverse cardiac remodelling, which compensates for the loss of cardiac cells, impairs cardiac function due to the non-contractile nature of fibrotic tissue.

Integrating Formative and Summative Clinical Skills Examinations to Promote Learning for Early Medical Students: A Mixed Methods Study.

Background: Medical educators aim to train students with high-quality clinical skills through the promotion of self-regulated learning and the development of lifelong learning skills. Formative clinical skills examinations (FCSE) allow for real-time learner-centered feedback and coaching which are key in promoting the development of expertise in early learners. This study assessed the impact of the integration of FCSE with learner-centered, real-time feedback and coaching based on an "educational plan-do-study-act" (PDSA) cycle on early medical students' experience and performance.

Approach to the patient with Childhood Interstitial and Diffuse Lung Disease.

Childhood Interstitial and Diffuse Lung Disease (chILD) encompasses a group of rare, chronic lung disorders in infants and children with overlapping clinical features but diverse etiologies. The clinical presentation of chILD is of chronic or recurring respiratory signs and symptoms, often including increased work of breathing and hypoxia, with diffuse radiographic abnormalities on chest imaging. Recognition can be challenging since some clinical features overlap with those of more common pediatric respiratory diseases including asthma and recurrent viral infections, among others.

Estimating the effect of nintedanib on forced vital capacity in children and adolescents with fibrosing interstitial lung disease using a Bayesian dynamic borrowing approach.

Background: The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predicted of 1.21 [95% confidence interval: -3.

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment.

Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab.

The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort.

Introduction: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders.

Methods: This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.

The lung in inborn errors of immunity: From clinical disease patterns to molecular pathogenesis.

In addition to being a vital organ for gas exchange, the lung is a crucial immune organ continuously exposed to the external environment. Genetic defects that impair immune function, called inborn errors of immunity (IEI), often have lung disease as the initial and/or primary manifestation. Common types of lung disease seen in IEI include infectious complications and a diverse group of diffuse interstitial lung diseases.

Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST.

Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN).

Using a Modified Delphi Methodology to Identify Essential Telemedicine Skills for Pediatric Residents.

Objective: Telemedicine use in pediatrics increased during the coronavirus disease-2019 (COVID-19) pandemic. Despite rapid uptake by pediatric residency programs, consensus on essential telemedicine skills for pediatric residents is lacking. We used a modified Delphi methodology to identify essential telemedicine skills and behaviors for pediatric residents.

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.

Impaired baseline lung function is associated with mortality after pediatric allogeneic hematopoietic cell transplantation (HCT), yet limited knowledge of the molecular pathways that characterize pretransplant lung function has hindered the development of lung-targeted interventions. In this study, we quantified the association between bronchoalveolar lavage (BAL) metatranscriptomes and paired pulmonary function tests performed a median of 1 to 2 weeks before allogeneic HCT in 104 children in The Netherlands. Abnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung injury-related mortality after HCT.

EphA2 Expression in Bone Sarcomas: Bioinformatic Analyses and Preclinical Characterization in Patient-Derived Models of Osteosarcoma, Ewing's Sarcoma and Chondrosarcoma.

Bone sarcomas are a group of heterogeneous malignant mesenchymal tumors. Complete surgical resection is still the cornerstone of treatment, but, in the advanced/unresectable setting, their management remains challenging and not significantly improved by target- and immuno-therapies. We focused on the tyrosine kinase Eph type-A receptor-2 (EphA2), a key oncoprotein implicated in self-renewal, angiogenesis, and metastasis, in several solid tumors and thus representing a novel potential therapeutic target.

Pulmonary surveillance in pediatric hematopoietic stem cell transplant: A multinational multidisciplinary survey.

Background: Hematopoietic Stem Cell Transplant (HSCT) is an established treatment for malignant and non-malignant conditions and pulmonary disease is a leading cause of late term morbidity and mortality. Accurate and early detection of pulmonary complications is a critical step in improving long term outcomes. Existing guidelines for surveillance of pulmonary complications post-HSCT contain conflicting recommendations.

Recruitment, Infiltration, and Cytotoxicity of HLA-Independent Killer Lymphocytes in Three-Dimensional Melanoma Models.

Cancer adoptive cell therapy (ACT) with HLA-independent tumor killer lymphocytes is a promising approach, with intrinsic features potentially addressing crucial tumor-escape mechanisms of checkpoint inhibitors. Cytokine-induced Killer (CIK) and Natural Killer (NK) lymphocytes share similar tumor-killing mechanisms, with preclinical evidence of intense activity against multiple solid tumors and currently testing in clinical studies. To improve the effective clinical translation of such ACT approaches, several fundamental questions still need to be addressed within appropriate preclinical contexts, capable of overcoming limitations imposed by most traditional two-dimensional assays.

Could the musk compound tonalide affect physiological functions and act as an endocrine disruptor in rainbow trout?

In the present study, the effect of polycyclic musk compound tonalide (AHTN) in two concentrations was studied in male rainbow trout (Oncorhynchus mykiss, Walbaum 1792). A feeding trial was conducted with AHTN incorporated into feed granules. One concentration was environmentally relevant (854 µg/kg); the second one was 10× higher (8699 µg/kg).

NT-proBNP levels and cardiopulmonary function in children with sickle cell disease.

Patients with sickle cell disease (SCD) are living longer and subsequently more apt to develop cardiopulmonary dysfunction. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels have been used in adults with SCD to assess for pulmonary hypertension and mortality. While the incidence of PH is low in pediatrics, it is reasonable to presume that NT-proBNP levels can be used to assess risk for the development of cardiopulmonary morbidity.

CSPG4-Specific CAR.CIK Lymphocytes as a Novel Therapy for the Treatment of Multiple Soft-Tissue Sarcoma Histotypes.

Purpose: No effective therapy is available for unresectable soft-tissue sarcomas (STS). This unmet clinical need prompted us to test whether chondroitin sulfate proteoglycan 4 (CSPG4)-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CAR.CIK) are effective in eliminating tumor cells derived from multiple STS histotypes and in immunodeficient mice.

Overview of the ChILD Research Network: A roadmap for progress and success in defining rare diseases.

Children's interstitial and diffuse lung diseases are a diverse group of rare lung disorders that present in childhood with diffuse pulmonary infiltrates and respiratory signs and symptoms. Children with these disorders face high morbidity and mortality and their families must cope with overwhelming uncertainty. Physicians caring for these patients are challenged by a paucity of directed therapies, or even understanding of natural history.

Highly Sensitive Blocker Displacement Amplification and Droplet Digital PCR Reveal Low-Level Parental FOXF1 Somatic Mosaicism in Families with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.

Detection of low-level somatic mosaicism [alternate allele fraction (AAF) ≤ 10%] in parents of affected individuals with the apparent de novo pathogenic variants enables more accurate estimate of recurrence risk. To date, only a few systematic analyses of low-level parental somatic mosaicism have been performed. Herein, highly sensitive blocker displacement amplification, droplet digital PCR, quantitative PCR, long-range PCR, and array comparative genomic hybridization were applied in families with alveolar capillary dysplasia with misalignment of pulmonary veins.

Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.

Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality. We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions.

Thoracic growth deficiency in childhood cancer survivors may cause overestimation of lung disease.

Introduction: Survivors of childhood cancers undergo routine pulmonary function testing as they are at an increased lifetime risk for significant lung disease. However, this population also demonstrates growth abnormalities that could influence the interpretation of these tests, as reference equations are based on standing height. We aim to determine the impact of the relative thoracic growth deficiency in childhood cancer survivors on the interpretation of pulmonary function testing.

Pulmonary Alveolar Proteinosis: A Case of Profound Hypoxemia in a Previously Healthy Teenager.

The profoundly hypoxemic child presents an interesting set of diagnostic and management challenges in the pediatric emergency department. While common pathologies including pneumonia, asthma, bronchiolitis, and pneumothoraces are managed using evidence-based algorithms, more enigmatic pathologies may present the treating physician with less diagnostic and therapeutic clarity. We present the case of a profoundly hypoxemic 16-year-old girl who presented in minimal distress, with oxyhemoglobin saturation of 63% on room air.