Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.

Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ.

Can Caregivers Forecast Their Child's Postoperative Disability After Elective Orthopedic Surgery?

Background While there has been a growing emphasis on evaluating the patient's perspective of health outcomes, caregiver expectations of post-orthopedic procedure disability and pain in a pediatric population are yet to be investigated. This study evaluates whether caregivers' preoperative expectations of pain and function differ from their child's early outcomes after surgical orthopedic intervention. Methodology Patients eight to 18 years old undergoing elective orthopedic surgery were enrolled.

Improving Patient Access to Primary Care Providers Using a Pharmacist-Physician Co-Visit Model.

: Implementation of a clinical pharmacist in the primary care setting can offset provider time spent managing chronic diseases using Collaborative Practice Agreements (CPAs). The pharmacist-physician co-visit model presents an opportunity for pharmacists to increase patient access to their primary care provider (PCP). Studies of the co-visit model show that co-visits increase clinic efficiency by allowing the PCP to see additional patients and achieve more health care goals compared with independent visits.

Parent psychological distress and parent-child relationships two years into the COVID-19 pandemic: Results from a Canadian cross-sectional study.

Background: Mental health impacts of the COVID-19 pandemic have not been felt equally within populations. Parents with children living at home were early on identified as a population at heightened mental health risk, with concerns about the potential long-term impacts of the pandemic on parents' mental health, family functioning, and children's well-being. This study investigates impacts of the pandemic on parents' psychological distress, contextual sources of distress, and associations with family functioning nearly two years into the pandemic.

Métis health in Canada: a scoping review of Métis-specific health literature.

Background: Métis are a culturally unique and distinct population, yet little research has evaluated their health separate from the broader Indigenous population. We sought to explore current literature regarding the health of Métis Peoples in Canada and identify potential trends and gaps.

Methods: Using the Arksey-O'Malley, 5-stage, scoping review method, we searched PubMed, MEDLINE, iPortal Indigenous Articles Portal Research Tool and pertinent reference lists using the terms "Métis," "health" and "Canada.

PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells.

Unlabelled: Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% of patients with NSCLC, with higher frequency in lung squamous carcinomas (LUSC). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy.

Cannabidiol Use Patterns and Efficacy for Children Who Have Cerebral Palsy.

Cannabidiol (CBD)-containing supplements are used by children with cerebral palsy (CP), but the prevalence and efficacy of their use have not been studied. We sought to describe CBD use patterns and perceived efficacy in the pediatric population with CP, evaluating any association between CBD use and health-related quality of life. Patients with CP were prospectively enrolled, and caregivers were offered the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) Questionnaire and a survey assessing CBD use.

Impact of the COVID-19 pandemic on alcohol or drug use symptoms and service need among youth: a cross-sectional sample from British Columbia, Canada.

Background: Concerns about youth alcohol and drug use have risen since the declaration of the global COVID-19 pandemic due to the pandemic's impact on known risk and protective factors for substance use. However, the pandemic's immediate and long-term impact on youths' substance use patterns has been less clear. Thus, this study sought to determine how the COVID-19 pandemic impacted alcohol or drug use and its risk and protective factors among youth accessing integrated youth services.

A Pilot Program: Remote Summer Program to Improve Opportunity and Mentorship Among Underrepresented Students Pursuing Orthopaedic Surgery.

Unlabelled: The purpose of this study was to evaluate the impact of an 8-week remote summer program in supporting underrepresented students interested in orthopaedic surgery.

Methods: We received 115 applications, and a total of 17 students participated in the program (14.8%).

Virtual Reality Reduces Fear and Anxiety During Pediatric Orthopaedic Cast Room Procedures: A Randomized Controlled Trial.

Background: Virtual Reality (VR) has been used as a distraction tool in various medical settings to reduce pain and anxiety associated with procedures. This study evaluates the effectiveness of VR as a distraction tool for decreasing fear, anxiety, and pain in pediatric patients undergoing common outpatient orthopaedic procedures.

Methods: A total of 210 patients were recruited from a single orthopaedic clinic between October 2017 and July 2019.

GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition.

Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival.

Use of Bedside Entertainment and Relaxation Theater (BERT) to Reduce Fear and Anxiety Associated With Outpatient Procedures in Pediatric Orthopaedics.

Background: The aim of the present study was to evaluate the effectiveness of the Bedside Entertainment and Relaxation Theater (BERT) on fear, anxiety, and pain outcomes in pediatric orthopaedic patients associated with cast removal and/or pin removal in the outpatient clinic setting.

Methods: A total of 66 pediatric patients between the ages of 2 and 6 undergoing clinic procedures were recruited for this study and randomized into the control group or the intervention (BERT) group. Patients in the control group received standard of care during the cast room procedure; patients in the BERT group were given headphones and watched a movie on a projector during the procedure.

Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response .

In lung adenocarcinoma, oncogenic mutations co-occur with many tumor suppressor gene alterations; however, the extent to which these contribute to tumor growth and response to therapy remains largely unknown. By quantifying the effects of inactivating 10 putative tumor suppressor genes in a mouse model of EGFR-driven -deficient lung adenocarcinoma, we found that , or inactivation strongly promoted tumor growth. Unexpectedly, inactivation of or the strongest drivers of growth in a KRAS-driven model-reduced EGFR-driven tumor growth.

Prevalence of Female Athlete Triad Risk Factors and Iron Supplementation Among High School Distance Runners: Results From a Triad Risk Screening Tool.

Background: Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population.

Purpose: To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score.

Deciding without data: clinical decision-making in pediatric orthopedic surgery.

Objective: Identifying when and how often decisions are made based on high-quality evidence can inform the development of evidence-based treatment plans and care pathways, which have been shown to improve quality of care and patient safety. Evidence to guide decision-making, national guidelines and clinical pathways for many conditions in pediatric orthopedic surgery are limited. This study investigated decision-making rationale and quantified the evidence supporting decisions made by pediatric orthopedic surgeons in an outpatient clinic.

Disaggregating Hispanic American Cancer Mortality Burden by Detailed Ethnicity.

Background: Hispanics are the largest minority population in the United States (18%). They represent a heterogeneous and growing population. Cancer is the leading cause of death among Hispanics, yet few studies have described cancer mortality burden by specific Hispanic group nationwide.

Comparison of Ideal Cardiovascular Health Attainment and Acculturation among Asian Americans and Latinos.

Objective: To determine the association between language and ideal cardiovascular health among Asian Americans and Latinos.

Design/study Participants: Cross-sectional study using 2011-2016 National Health and Nutrition Examination Survey of Asian Americans (n=2,009) and Latinos (n=3,906).

Interventions: Participants were classified according to language spoken at home (only/mostly English spoken, both English and native language spoken equally, or mostly/only native language spoken).

Years of Potential Life Lost Because of Cardiovascular Disease in Asian-American Subgroups, 2003-2012.

Background Asian-American subgroups (Asian-Indian, Chinese, Filipino, Korean, Japanese, and Vietnamese) display varied cardiovascular disease mortality patterns, especially at younger ages. This study aims to examine the years of potential life lost because of ischemic heart disease and cerebrovascular disease among the 6 largest Asian-American subgroups compared with non-Hispanic whites. Methods and Results We used National Center for Health Statistics Multiple Causes of Death mortality files from 2003 to 2012 to calculate race-specific life expectancy, mean years of potential life lost, and years of potential life lost per 100 000 population for each Asian subgroup and non-Hispanic whites.

Loss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia.

The TAM receptor, Axl, has been implicated as a candidate entry receptor for Zika virus (ZIKV) infection but has been shown as inessential for virus infection in mice. To probe the role of Axl in murine ZIKV infection, we developed a mouse model lacking the Axl receptor and the interferon alpha/beta receptor (IfnarAxl), conferring susceptibility to ZIKV. This model validated that Axl is not required for murine ZIKV infection and that mice lacking Axl are resistant to ZIKV pathogenesis.

Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes.

Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression.

Diabetes-attributable mortality in the United States from 2003 to 2016 using a multiple-cause-of-death approach.

Aims: Deaths attributable to diabetes may be underestimated using an underlying cause of death (COD) approach in U.S. death records.

Socioeconomic Differences in the Epidemiologic Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States, 2003 to 2015: An Observational Study.

Background: Recent data suggest that the United States is in the midst of an epidemiologic transition in the leading cause of death.

Objective: To examine county-level sociodemographic differences in the transition from heart disease to cancer as the leading cause of death in the United States.

Design: Observational study.