Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML): A Multicenter Retrospective Analysis.

Background: Addition of midostaurin to standard "7+3" (cytarabine and anthracycline) significantly prolongs overall and event-free survival. At University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (R/R) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated. There is limited data on the use of FLT3-inhibitors with high-dose cytarabine regimens in AML.

Risk of Atherosclerotic Cardiovascular Disease After Chronic Obstructive Pulmonary Disease Hospitalization among Primary and Secondary Prevention Older Adults.

Background: Meta-analyses have suggested that the risk of cardiovascular disease events is significantly higher after a chronic obstructive pulmonary disease (COPD) exacerbation, but the populations at highest risk have not been well characterized to date.

Methods And Results: The authors analyzed the risk of atherosclerotic cardiovascular disease (ASCVD) hospitalizations after COPD hospitalization compared with before COPD hospitalization and patient factors associated with ASCVD hospitalizations after COPD hospitalization among 2 high-risk patient cohorts. The primary outcome was risk of an ASCVD hospitalization composite outcome (myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, stroke, transient ischemic accident) after COPD hospitalization relative to before COPD hospitalization.

Pediatric Craniofacial Injuries Involving Alcohol: An Epidemiologic Study.

Introduction: Alcohol intoxication significantly increases an individual's risk for a variety of injuries including craniofacial injuries, although this research is limited to adults. Further research is needed on pediatric craniofacial injuries related to alcohol use in children, a group inherently different in anatomy and developmental considerations from adults. This study aims to identify alcohol-related craniofacial injury patterns, injury mechanisms, and patient disposition in the pediatric population presenting to the emergency department.

Knee-Related Patient-Reported Outcome Measures for Young Adults: A Scoping Meta-Review.

Background: There is a lack of patient-reported outcome measures (PROMs) research on young adults and knee disorders. This scoping meta-review examined a young adult population and aimed to (1) provide an overview of knee-related PROMs research and (2) evaluate the measurement properties of the five most evaluated knee-related PROMs relevant for individual care and group-level analysis.

Methods: A systematic search of the PubMed and COSMIN databases was conducted on 18 September 2023 and updated on 25 November 2024 to identify systematic reviews of knee-related PROMs in young adults.

Stimulus-invariant aspects of the retinal code drive discriminability of natural scenes.

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into the static and dynamic features of the population code in retinal ganglion cells (RGCs), less is known about how populations form both flexible and reliable encoding in natural moving scenes.

Omission of postoperative radiotherapy after breast-conserving surgery in low-risk breast cancer.

Background: This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women ≥ 65 years with low-risk, estrogen receptor (ER)-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy.

Methods: Eligible patients were women ≥ 65 years with unifocal, non-lobular, grade 1 or 2, ER-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for five years. Patients were followed up with mammography at least annually for 10 years.

Accelerating evidence generation: Addressing critical challenges and charting a path forward.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25-26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs.

Basiliximab induction immunosuppression and lung transplant outcomes: Propensity analysis in a multicenter cohort.

Background: Basiliximab induction immunosuppression is increasingly employed in lung transplant recipients despite limited prospective evidence to support its use in this population. We sought to determine the relationship between basiliximab induction and development of acute rejection, chronic lung allograft dysfunction, and other clinically relevant outcomes in a multicenter lung transplant cohort with variable induction practice patterns.

Methods: We applied propensity-based statistical methods to rigorous, prospectively collected longitudinal data from 768 newly transplanted adult lung recipients at 5 North American centers (368 who received basiliximab induction immunosuppression and 400 who received no induction immunosuppression).

Association of socioeconomic status with clinical characteristics, care quality and outcomes in patients undergoing transcatheter aortic valve implantation.

Background: Socioeconomic status (SES) is an important determinant of healthcare outcomes in many settings, but few studies have evaluated the impact of SES among patients with aortic stenosis (AS). We sought to explore the association between SES and clinical characteristics, care quality and outcomes among patients undergoing transcatheter aortic valve implantation (TAVI) for severe AS.

Methods: Consecutive patients undergoing TAVI for severe AS at three hospitals between August 2008 and February 2023 were prospectively enrolled in a multicentre registry.

Maternal high fat diet exposure modifies amniotic fluid metabolites and expands group 3 innate lymphoid cells dependent on the maternal microbiome and MyD88-signaling.

Background: Maternal high fat diet (mHFD) exposure expands IL-17 producing group 3 innate lymphoid cells (IL17 ILC3) in the small intestine of neonatal murine offspring and increases their susceptibility to intestinal inflammation. How mHFD modulates innate immunity in the fetal offspring remains unclear.

Methods: Dams were exposed to 60% high fat diet or maintained on regular diet (RD) prior to and during mating.

Leadership training in emergency medicine: A national survey.

Background: Emergency medicine (EM) is a uniquely stressful environment in which leadership training could improve individual and team performance, patient outcomes, well-being, and EM career intentions. The primary aim was to evaluate EM-specific leadership training (EMLeaders) compared to no leadership training. A secondary comparison was with other forms of leadership training.

Multi-indication Evidence Synthesis in Oncology Health Technology Assessment: Meta-analysis Methods and Their Application to a Case Study of Bevacizumab.

Background: Multi-indication cancer drugs receive licensing extensions to include additional indications, as trial evidence on treatment effectiveness accumulates. We investigate how sharing information across indications can strengthen the inferences supporting health technology assessment (HTA).

Methods: We applied meta-analytic methods to randomized trial data on bevacizumab, to share information across oncology indications on the treatment effect on overall survival (OS) or progression-free survival (PFS) and on the surrogate relationship between effects on PFS and OS.

Integrated hip surveillance pathways for pain, function and quality of life in children with Cerebral Palsy: A systematic literature review.

Aim: To determine the effectiveness of integrated hip surveillance pathways on pain, function and quality of life (QOL) in children with Cerebral Palsy (CP).

Method: A systematic literature review, designed, conducted and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Inclusion Criteria: confirmed CP diagnosis, management under recognised international hip surveillance pathways, outcome measures of hip displacement plus at least one other relevant to pain, function or QOL.

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer.

Blue GaN-based DFB laser diode with sub-MHz linewidth.

Distributed feedback laser diodes (DFBs) serve as simple, compact, narrow-band light sources supporting a wide range of photonic applications. Typical linewidths are on the order of sub-MHz for free-running III-V DFBs at infrared wavelengths, but linewidths of short-wavelength GaN-based DFBs are considerably worse or unreported. Here, we present a free-running InGaN DFB operating at 443 nm with an intrinsic linewidth of 685 kHz at a continuous wave output power of 40 mW.

Adverse effects of CXCR2 deficiency in mice reared under non-gnotobiotic conditions.

The family of pro-inflammatory and pro-angiogenic chemokines including Interleukin-8 (IL-8, aka CXCL8) and its homologues (CXCL1,2,3,5,6, and 7) exhibit promiscuous binding and activation of several G-protein-coupled receptors (i.e., CXCR2, CXCR1, and the atypical chemokine receptor (ACKR1)).

Prognosis and Risks for Probable Chronic Lung Allograft Dysfunction: A Prospective Multicenter Study.

Rationale: Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain.

Symptoms of Anxiety and Depression in Patients Who Underwent Transcatheter Aortic Valve Implantation: The SAD-TAVI Study.

Symptoms of anxiety and/or depression (SAD) commonly co-exist in severe aortic stenosis. In patients who underwent transcatheter aortic valve implantation (TAVI), these symptoms are associated with increased morbidity and mortality. Despite this, mental health remains under-researched in the TAVI literature.

Identification and validation of a threshold for early posttransplant bronchoalveolar fluid hyaluronan that distinguishes lung recipients at risk for chronic lung allograft dysfunction.

Background: Few tools exist for the early identification of patients at risk for chronic lung allograft dysfunction (CLAD). We previously showed hyaluronan (HA), a matrix molecule that regulates lung inflammation and fibrosis, accumulates in bronchoalveolar lavage fluid (BALF) and blood in CLAD. We aimed to determine if early posttransplant HA elevations inform CLAD risk.

Graft Loss in Pediatric and Young Adult Kidney Transplantation in New Zealand: Who Is at Greatest Risk and When?

Background: Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post-KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA).

Distinct roles for the domains of the mitochondrial aspartate/glutamate carrier citrin in organellar localization and substrate transport.

Objective: Citrin, the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), is structurally and mechanistically the most complex SLC25 family member, because it consists of three domains and forms a homo-dimer. Each protomer has an N-terminal calcium-binding domain with EF-hands, followed by a substrate-transporting carrier domain and a C-terminal domain with an amphipathic helix. The absence or dysfunction of citrin leads to citrin deficiency, a highly prevalent pan-ethnic mitochondrial disease.

Associations of circulating matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases with clinically relevant outcomes in idiopathic pulmonary fibrosis: Data from the IPF-PRO Registry.

Introduction: We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry.

Methods: MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant).