ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.

DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.

Ternary complex components responsible for rapid LDL internalization as biomarkers for breast cancer associated with proliferation and early recurrence.

The ternary complex of PGRMC1-σ2R/TMEM97-LDLR has recently been discovered and plays a role in cholesterol transport. This study investigated whether individual components of that complex are prognostic breast cancer biomarkers and defined expression in established molecular subtypes. 4,463 invasive breast cancers were analyzed as a function of molecular and phenotypic markers, estimates of cellular proliferation, and recurrence-free survival.

A Randomized Controlled Trial of Cognitive Behavioral Therapy for Insomnia During Early Recovery from Alcohol Use Disorder Among Veterans.

Study Objectives: 1) To determine the efficacy of Cognitive Behavioral Therapy for Insomnia (CBT-I) for improving insomnia, alcohol-related outcomes, and daytime functioning at post-treatment and at 3- and 6-month follow-up, in a largely African American Veteran sample; 2) Evaluate whether improvement in insomnia is associated with a reduction in alcohol-related outcomes post-treatment.

Methods: An RCT of CBT-I (n = 31) compared to Quasi-Desensitization therapy (QDT, n = 32), eight weekly in-person sessions, with assessments at baseline, end of treatment (8 weeks), and 3- and 6-months post-treatment. Primary outcomes were the Insomnia Severity Index (ISI) total score, and Percent Days Abstinent (PDA).

Liver Transplant From a Deceased Donor With Cystinosis: A Case Report.

Many inherited metabolic disorders (IMD) are associated with end-organ damage necessitating organ transplantation. Although utilization of deceased donors with history of IMD warrants caution, there may be circumstances under which such donors could be considered as suitable organ donor candidates. We present the first known report of liver transplantation from a deceased donor with cystinosis.

SGLT2i and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction in Patients With Diabetes.

Background: Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects.

Objectives: This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure.

Colorectal Cancer and Quality of Life: A Medicare Advantage Study by Race, Ethnicity, and Language.

Background And Methods: Colorectal cancer (CRC) treatment can influence health-related quality of life (HRQOL). This study examined HRQOL among older adults undergoing CRC treatment, and the conditional effects of race, ethnicity, and primary language. We conducted a retrospective cohort study of Medicare Advantage enrollees ≥ 65 years old who completed the Medicare Health Outcomes Survey (MHOS) (2016-2020).

Delayed or forgone medical care associated with increased resource utilization and health care expenditures among patients with peripheral artery disease in the United States.

Background: PAD affects >12 million Americans and poses significant financial burdens on patients, but the relationship between delayed/forgone (D/F) care and resource use in this population is unknown. We sought to assess the relationship between D/F care, resource use, and health care expenditures among patients with PAD.

Methods: Adults with PAD in the US were identified in the Medical Expenditure Panel Survey for years 2007-2017.

An 18-Year Review of Hemoglobinopathy Proficiency Testing: Recommendations From the College of American Pathologists Hematology and Clinical Microscopy Committee.

Context.—: The College of American Pathologists Hematology and Clinical Microscopy Committee implemented a hemoglobinopathy proficiency testing and education program to monitor and assess the performance of participating laboratories.

Objective.

Child Maltreatment Evaluations Following Out-of-Hospital Cardiac Arrests.

Objectives: In children admitted after an out-of-hospital cardiac arrest (OHCA), this study 1) determines the proportion that undergo: physical abuse and toxin exposure evaluation, child protection team (CPT) consultation, and child protective services (CPS) referral, and 2) evaluates the association between demographic, social, clinical characteristics with CPT consultation and CPS referral.

Methods: Retrospective chart review was conducted of children < 4 years old admitted following an OHCA between November 2012 and February 2023. Associations between demographics, caregiver social risk factors, and clinical characteristics with CPT consultation and CPS referral were examined using logistic regression.

Disorders of Lymphatic Architecture and Flow in Critical Illness.

Objectives: To provide a narrative review of disordered lymphatic dynamics and its impact on critical care relevant condition management.

Data Sources: Detailed search strategy using PubMed and Ovid Medline for English language articles (2013-2023) describing congenital or acquired lymphatic abnormalities including lymphatic duct absence, injury, leak, or obstruction and their associated clinical conditions that might be managed by a critical care medicine practitioner.

Study Selection: Studies that specifically addressed abnormalities of lymphatic flow and their management were selected.

Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function.

Complications of percutaneous coronary intervention.

Complications of percutaneous coronary intervention (PCI) can lead to significant morbidity and mortality. In-depth understanding of the mechanisms and management options of these complications as well as timely recognition and action can sometimes be lifesaving. In this review we discuss the mechanisms, prevention methods, diagnosis, and management of three major PCI complications: a) perforation b) acute vessel closure, and c) equipment loss.

High-throughput determination of exchange rates of unmodified and PTM-containing peptides using HX-MS.

Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally-occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values.

A Qualitative Assessment of Barriers, Facilitators, and Outcomes in a Simulation-Based Collaborative Quality Improvement Program: The ImPACTS Project.

Objectives: ImPACTS (Improving Acute Care Through Simulation) is a collaborative simulation-based program partnering pediatric specialty centers ("hubs") with general emergency departments (GEDs) to improve pediatric acute care. Objective measurements of ImPACTS, such as evaluating Pediatric Readiness Score (PRS) and simulation-based outcome improvements, have been reported previously. Barriers to and facilitators of program involvement and the downstream effects of the program have not been previously described.

CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.

Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.

Continuous Glucose Monitoring Attrition in Youth With Type 1 Diabetes.

Purpose: The purpose of the study was to identify the most common reasons for and timing of continuous glucose monitoring (CGM) attrition in youth with type 1 diabetes (T1DM).

Methods: This single center retrospective chart review included youth with T1DM <22 years seen between November 1, 2021, and October 31, 2022. Data were gathered from CGM cloud-based software and the electronic medical record.

Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.

While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and refractory disease remain a significant therapeutic challenge. This is particularly true for patients with T-cell ALL and LBL, where survival for patients with relapsed/refractory disease remains dismal. Recent efforts to comprehensively profile the genomics of T-ALL/LBL to improve understanding of disease biology have enhanced our ability to identify high-risk patients at diagnosis who are more likely to relapse and have also identified novel targets for precision medicines.

Lymph Node Dissection for Melanoma: Contemporary Trends in Postoperative Outcomes and Patient Selection With Reduced Case Volumes in the Post-MSLT2 Era.

Background And Objectives: Since the publication of the German Cooperative Oncology Group Selective Lymphadenectomy Trial and Multicenter Selective Lymphadenectomy Trial II (MSLT2) trials, the treatment paradigm for node-positive melanoma has shifted from completion lymph node dissection (LND) to nodal ultrasound surveillance. We sought to identify the impact of this practice change on postoperative outcomes in a national cohort.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients diagnosed with truncal/extremity malignant melanoma who underwent axillary/inguinal LND.

Phenotypic Expansion: Fetus With Cole-Carpenter Type 2 Presenting With Novel Neonatal Lethal Skeletal Dysplasia.

We report a 28-year-old G2P0 at 24 weeks 5 days who presented for evaluation secondary to suspected skeletal dysplasia in her fetus. Fetal ultrasound imaging demonstrated foreshortened long bones by 9-10 weeks, multiple bowing deformities and fractures, 11 foreshortened paired ribs with fractures, decreased skull mineralization, frontal bossing, enlarged cavum septum pellucidi, and severe fetal growth restriction (< 2%). Findings were concerning for life limiting condition with thoracic circumference < 2.