Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models.

The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses ( wild-type, -mutated, -mutated, and -mutated).

Healthy at Home for COPD: An Integrated Digital Monitoring, Treatment, and Pulmonary Rehabilitation Intervention.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality in the United States. Frequent exacerbations result in higher use of emergency services and hospitalizations, leading to poor patient outcomes and high costs.

Objective: Demonstrate the feasibility of a multimodal, digitally enhanced remote monitoring, treatment, and tele-pulmonary rehabilitation intervention among patients with COPD.

A Coproduced Family Reporting Intervention to Improve Safety Surveillance and Reduce Disparities.

Objectives: Examine family safety-reporting after implementing a parent-nurse-physician-leader coproduced, health literacy-informed, family safety-reporting intervention for hospitalized families of children with medical complexity.

Methods: We implemented an English and Spanish mobile family-safety-reporting tool, staff and family education, and process for sharing comments with unit leaders on a dedicated inpatient complex care service at a pediatric hospital. Families shared safety concerns via predischarge surveys (baseline and intervention) and mobile tool (intervention).

Receptor Discordance in Metastatic Breast Cancer; a review of clinical and genetic subtype alterations from primary to metastatic disease.

Purpose: Receptor and subtype discordance between primary breast tumours and metastases is a frequently reported phenomenon. The aim of this article is to review the current evidence on receptor discordance in metastatic breast cancer and to explore the benefit of performing a repeat biopsy in this context.

Methods: Searches were undertaken on PubMed and Clinicaltrials.

Predictive value of pretreatment circulating inflammatory response markers in the neoadjuvant treatment of breast cancer: meta-analysis.

Background: Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this.

Methods: A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy.

Rationale and Design of Healthy at Home for COPD: an Integrated Remote Patient Monitoring and Virtual Pulmonary Rehabilitation Pilot Study.

Chronic Obstructive Pulmonary Disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care.

Genome Sequencing of Multiple Primary Lung Cancers Harbouring Mixed Histology and Spontaneously Regressing Small-Cell Lung Cancer.

Up to 15% of lung cancer patients present two or more anatomically separate primary lung lesions, known as multiple primary lung cancers (MPLCs). While surgical resection or stereotactic body radiation therapy (SBRT) is the standard of care for most early-stage lung cancer cases, this may not be an option for patients with widespread tumours, highlighting the need for the improved targeted management of MPLC patients, which remains challenging. Moreover, the spontaneous regression (SR) of small-cell lung cancer (SCLC) is rare, with only four cases accounted for between 1988 and 2018.

KMT2C and KMT2D aberrations in breast cancer.

KMT2C and KMT2D are histone lysine methyltransferases responsible for the monomethylation of histone 3 lysine 4 (H3K4) residues at gene enhancer sites. KMT2C/D are the most frequently mutated histone methyltransferases (HMTs) in breast cancer, occurring at frequencies of 10-20% collectively. Frequent damaging and truncating somatic mutations indicate a tumour-suppressive role of KMT2C/D in breast oncogenesis.

Management of Heat-Related Illness and Injury in the ICU: A Concise Definitive Review.

Objectives: The increasing frequency of extreme heat events has led to a growing number of heat-related injuries and illnesses in ICUs. The objective of this review was to summarize and critically appraise evidence for the management of heat-related illnesses and injuries for critical care multiprofessionals.

Data Sources: Ovid Medline, Embase, Cochrane Clinical Trials Register, Cumulative Index to Nursing and Allied Health Literature, and ClinicalTrials.

Neoadjuvant trastuzumab deruxtecan (T-DXd) with response-directed definitive therapy in early stage HER2-positive breast cancer: a phase II study protocol (SHAMROCK study).

Background: The current standard of care in the neoadjuvant setting for high-risk HER2-positive (HER2 +) breast cancer is to combine systemic chemotherapy with dual HER2 blockade, trastuzumab and pertuzumab. Targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer. To improve treatment-associated toxicity, chemotherapy-sparing approaches are currently being investigated.

Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.

Clinical algorithms, or "pathways," promote the delivery of medical care that is consistent and equitable. Race, ethnicity, and/or ancestry terms are sometimes included in these types of guidelines, but it is unclear if this is appropriate for clinical decision-making. At our institution, we developed and applied a structured framework to determine whether race, ethnicity, or ancestry terms identified in our clinical pathways library should be retained, modified, or removed.

Impairment Types and Combinations Among Adolescents and Young Adults with Disabilities: Colorado 2014-2018.

Objective: Understanding the types of functional challenges faced by adolescents and young adults with disabilities (AYA-WD) can help payers, clinicians, community-based service providers, and policymakers recognize and meet needs. This paper describes state-level prevalence rates for 1) AYA-WD overall and for 2) impairment types singly and in combinations; and 3) examines how rates may differ between those insured by Medicaid versus commercial insurance.

Methods: This descriptive study uses Colorado's All Payer Claims Dataset 2014-2018 to identify insured 10- to 26-year-olds (Medicaid only: 333,931; commercially only: 392,444).

Impact of Standardized Multidisciplinary Critical Care Training on Confidence with Critical Illness and Attitudes Towards Interprofessional Education and Multidisciplinary Care.

Introduction: The Fundamental Critical Care Support Course (FCCS) is a standardized multidisciplinary program designed to educate participants on the basics of identification and management of patients with critical illness. Our objective was to evaluate the effect of FCCS participation on confidence in the assessment and management of critically ill patients and attitudes towards multidisciplinary education and interprofessional care in a multidisciplinary group of participants.

Methods: Participants enrolled in the FCCS course from May 2018 to November 2019 were solicited to participate in a series of surveys evaluating their course experience and confidence in critical care.

Efficacy and Safety of Trastuzumab Deruxtecan in Breast Cancer: A Systematic Review and Meta-Analysis.

Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer.

Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.

HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients.

Protein Tyrosine Phosphatase Non-Receptor 11 (/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC).

encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of and MEK. /Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)).

Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer.

Background: Studies have demonstrated the efficacy of Palbociclib (CDK 4/6 inhibitor), Gedatolisib (PI3K/mTOR dual inhibitor) and PD0325901 (MEK1/2 inhibitor) in colorectal cancer (CRC), however single agent therapeutics are often limited by the development of resistance.

Methods: We compared the anti-proliferative effects of the combination of Gedatolisib and Palbociclib and Gedatolisib and PD0325901 in five CRC cell lines with varying mutational background and tested their combinations on total and phosphoprotein levels of signaling pathway proteins.

Results: The combination of Palbociclib and Gedatolisib was superior to the combination of Palbociclib and PD0325901.

Predictors of Subspecialty Appointment Scheduling and Completion for Patients Referred From a Pediatric Primary Care Clinic.

Failure to complete subspecialty referrals decreases access to subspecialty care and may endanger patient safety. We conducted a retrospective analysis of new patient referrals made to the 14 most common referral departments at Boston Children's Hospital from January 1 to December 31, 2017. The sample included 2031 patient referrals.

Improving Use of Antibiotics for Pediatric Pneumonia in Community Hospital Emergency Departments.

Background And Objectives: The majority of pediatric patients present to community-hospital emergency departments (EDs). Pneumonia is among the most common reasons for ED visits; however, prescribing narrow-spectrum antibiotics occurs at rates below established best practices. We sought to increase prescription of narrow-spectrum antibiotics for pediatric pneumonia in 5 community hospital EDs using an interdisciplinary learning collaborative.

Review of the status of neoadjuvant therapy in HER2-positive breast cancer.

Purpose: The development of human epidermal growth factor receptor 2 (HER2)-directed therapies has revolutionized the treatment of HER2-positive breast cancer. The aim of this article is to review the continually evolving treatment strategies in the neoadjuvant setting of HER2-positive breast cancer, as well as the current challenges and future perspectives.

Methods: Searches were undertaken on PubMed and Clinicaltrials.