Updated Geriatrics Competencies for Graduating Medical Students: Training Physicians to Provide Age-Friendly Care.

Purpose: Medical student education in geriatrics is a critical need for every doctor-in-training as the population ages, with fewer than 7,000 geriatricians, and older patients, who now approach 20% of the U.S. population, having unique health care needs.

Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial.

Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening.

Background & Aims: Liver cancer-related deaths are projected to exceed one million annually by 2030. Existing therapies have significant limitations, including severe side effects and inconsistent efficacy. Innovative therapeutic approaches to address primary liver cancer (PLC) have led to the ongoing development of tumor-derived organoids.

Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury.

Tissue engineering provides a path forward for emerging personalized medicine therapies as well as the ability to bring about cures for diseases or chronic injuries. Traumatic spinal cord injuries (SCIs) are an example of a chronic injury in which no cure or complete functional recovery treatment has been developed. In part, this has been due to the complex and interconnected nature of the central nervous system (CNS), the cellular makeup, its extracellular matrix (ECM), and the injury site pathophysiology.

Release of Zafirlukast from Electrospun Polyisobutylene-Based Fiber Mats to Reduce Capsular Contracture of Silicone Breast Prostheses.

Silicone rubber tissue expanders and breast implants are associated with chronic inflammation, leading to the formation of fibrous capsules. If the inflammation is left untreated, the fibrous capsules can become hard and brittle and lead to formation of capsular contracture. When capsular contracture occurs, implant failure and reoperation is unavoidable.

Chitosan-based multifunctional oxygenating antibiotic hydrogel dressings for managing chronic infection in diabetic wounds.

Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB).

Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model.

Background: Syringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.

Four decades of progress in heart-lung transplantation: Two hundred seventy-one cases at a single institution.

Objective: The objective of this study is to evaluate survival for combined heart-lung transplant (HLTx) recipients across 4 decades at a single institution. We aim to summarize our contemporary practice based on more than 271 HLTx procedures over 40 years.

Methods: Data were collected from a departmental database and the United Network for Organ Sharing.

Comparison of Engineered Liver 3D Models and the Role of Oxygenation for Patient-Derived Tumor Cells and Immortalized Cell Lines Cocultured with Tumor Stroma in the Detection of Hepatotoxins.

In metabolically active tumors, responses of cells to drugs are heavily influenced by oxygen availability via the surrounding vasculature alongside the extracellular matrix signaling. The objective of this study is to investigate hepatotoxicity by replicating critical features of hepatocellular carcinoma (HCC). This includes replicating 3D structures, metabolic activities, and tumor-specific markers.

Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation With or Without Prior Ventricular Assist Device.

Background: Both combined heart-kidney transplantation and ventricular assist devices (VADs) pose significant challenges, including sensitization, immunosuppressive treatment, and infrastructure demands. Despite these challenges, we hypothesized that the recipients of combined heart-kidney transplants with and without VADs would have equivalent survival. We aimed to compare the survival of heart-kidney transplant recipients with and without prior VAD placement.

Fabrication of oxygen-carrying microparticles functionalized with liver ECM-proteins to improve phenotypic three-dimensional in vitro liver assembly, function, and responses.

Oxygen and extracellular matrix (ECM)-derived biopolymers play vital roles in regulating many cellular functions in both the healthy and diseased liver. This study highlights the significance of synergistically tuning the internal microenvironment of three-dimensional (3D) cell aggregates composed of hepatocyte-like cells from the HepG2 human hepatocellular carcinoma cell line and hepatic stellate cells (HSCs) from the LX-2 cell line to enhance oxygen availability and phenotypic ECM ligand presentation for promoting the native metabolic functions of the human liver. First, fluorinated (PFC) chitosan microparticles (MPs) were generated with a microfluidic chip, then their oxygen transport properties were studied using a custom ruthenium-based oxygen sensing approach.

Surgical Management of Esophageal Perforation: Examining Trends in a Multi-Institutional Cohort.

Background: Esophageal perforations historically are associated with significant morbidity and mortality and generally require emergent intervention. The influence of improved diagnostic and therapeutic modalities available in recent years on management has not been examined. This study examined the surgical treatments and outcomes of a modern cohort.

Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice.

Background: The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS.

Methods: Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms.

Advancements in bacteriophage therapies and delivery for bacterial infection.

Having co-evolved with bacteria over hundreds of millions of years, bacteriophage are effective killers of specific bacterial hosts. Therefore, phage therapies for infection are a promising treatment avenue, can provide a solution for antibiotic resistant bacterial infections, and have specified targeting of infectious bacteria while allowing the natural microbiome to survive which systemic antibiotics often wipe out. Many phages have well studied genomes that can be modified to change target, widen target range, or change mode of action of killing bacterial hosts.

Osmotic Contribution of Synthesized Betaine by Choline Dehydrogenase Using and Models of Post-traumatic Syringomyelia.

Introduction: Syringomyelia (SM) is a debilitating spinal cord disorder in which a cyst, or syrinx, forms in the spinal cord parenchyma due to congenital and acquired causes. Over time syrinxes expand and elongate, which leads to compressing the neural tissues and a mild to severe range of symptoms. In prior omics studies, significant upregulation of betaine and its synthesis enzyme choline dehydrogenase (CHDH) were reported during syrinx formation/expansion in SM injured spinal cords, but the role of betaine regulation in SM etiology remains unclear.

Midterm Outcomes in Type A Aortic Dissection Repair With and Without Malperfusion in a Hybrid Operating Room.

Treatment approach to type A aortic dissection with malperfusion, immediate open aortic repair vs upfront endovascular treatment, remains controversial. From January 2017 to July 2021, 301 consecutive type A repairs were evaluated at our institution. Starting in 2019, all type A aortic dissections were performed in a fixed-fluoroscopy, hybrid operating room.

Biomechanical engineering analysis of commonly utilized mitral neochordae.

Objective: To evaluate the suture rupture forces of commonly clinically utilized neochord repair techniques to identify the most biomechanically resistant most biomechanically resistant technique.

Methods: Several types of neochord techniques (standard interrupted neochordae, continuous running neochordae, and loop technique), numbers of neochordae, and suture calibers (polytetrafluoroethylene CV-3 to CV-6) were compared. To perform the tests, both ends of the neochordae were loaded in a tensile force analysis machine.

Implementation and Effectiveness of Cognitive Behavioral Therapy for Insomnia in Geriatric Primary Care.

Objectives: We evaluated a plan for implementation and effectiveness of cognitive behavioral therapy for insomnia (CBT-I) in geriatric primary care by a geropsychologist.

Methods: The flow of referrals to a geropsychologist was tracked and, among those eligible and interested in participating, success in deprescribing sleep medications and the effectiveness of CBT-I were documented.

Results: Seventy patients were referred for evaluation of whom 62 were eligible for CBT-I; 34 began CBT-I and 29 completed a full course of treatment.

Modulatory Contribution of Oxygenating Hydrogels and Polyhexamethylene Biguanide on the Antimicrobial Potency of Neutrophil-like Cells.

Neutrophils are a first line of host defense against infection and utilize a series of oxygen-dependent processes to eliminate pathogens. Research suggests that oxygen availability can improve anti-infective mechanisms by promoting the formation of reactive oxygen species. Also, oxygen can synergistically upregulate the antibacterial properties of certain antibiotics against bacteria by altering their metabolism and causing an increase in the antibiotic uptake of bacteria.

Investigating Mechanisms of Subcutaneous Preconditioning Incubation for Neural Stem Cell Embedded Hydrogels.

Stem cells are a vital component of regenerative medicine therapies, however, only a fraction of stem cells delivered to the central nervous system following injury survive the inflammatory environment. Previously, we showed that subcutaneous preconditioning of neural stem cell (NSC) embedded hydrogels for 28 days improved spinal cord injury (SCI) functional outcomes over controls. Here, we investigated the mechanism of subcutaneous preconditioning of NSC-embedded hydrogels, with and without the known neurogenic cue, interferon gamma (IFN-γ), for 3, 14, or 28 days to refine and identify subcutaneous preconditioning conditions by measurement of neurogenic markers and cytokines.