Bridging Therapies-Ex Vivo Liver Xenoperfusion and the Role of Machine Perfusion: An Update.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models.

Exploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing.

The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing.

Large donor CRISPR for whole-CDS replacement of cell adhesion molecule LRRTM2.

The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2.

Endo-Bentall Repair: Early Results and Feasibility of a Physician-Constructed Endo-Bentall Device.

Objective: We present our experience with endovascular Bentall procedure (Endo-Bentall) using a modular valve conduit (Endo-Bentall) in high-risk patients with aortic root pathologies.

Methods: The physician constructed Endo-Bentall device is composed of a self-expanding transcatheter aortic valve (TAVR), aortic endovascular stent graft (TEVAR), and two wire-reinforced fenestrations for coronary artery stenting. The TAVR valve is sutured into an appropriately sized TEVAR graft.

From Zone -1 to Zone 3: Feasibility and Safety of Complex Endovascular Aortic Repairs in Type A Aortic Dissection.

Objective: Over 30% of patients presenting with acute type A aortic dissection (ATAAD) are considered high - risk or inoperable. This study aims to investigate the early and mid-term outcomes of complex endovascular aortic repair of aortic root, ascending aorta, and aortic arch among patients with ATAAD.

Methods: From January 2018 to January 2023, 29 patients who were considered high risk for open operation underwent endovascular aortic repair.

Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study.

Background: Authorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

Prevalence of Pulmonary Embolism in COVID-19 Positive Critically Ill Children.

Objectives: To investigate the prevalence of pulmonary embolism (PE) in children admitted to critical care diagnosed with COVID-19 infection.

Design: Retrospective database study.

Setting: Data reported to the Virtual Pediatric Systems, 2018-2021.

Systematic review of the effects of topical oxygen therapy on wound healing.

Background: Various adjunct therapies are available for wound healing in addition to standard care. Topical oxygen therapy (TCOT) is one such novel therapy. We conducted a systematic review and meta-analysis to evaluate the role of TCOT in the healing of cutaneous wounds of any etiology.

Prevalence of Pulmonary Embolism in COVID-19 Positive Critically Ill Children.

Objectives: To investigate the prevalence of pulmonary embolism (PE) in children admitted to critical care diagnosed with COVID-19 infection.

Design: Retrospective database study.

Setting: Data reported to the Virtual Pediatric Systems, 2018-2021.

Association of Step Count with Cardiorespiratory Fitness: Results from the Virtual 2-Minute Step Test.

Objective: To test the hypothesis that step count based on a virtual 2-minute step test (2MST) predicts cardiorespiratory fitness (CRF).

Design: Cross-sectional study.

Setting: Veteran Affairs Medical Centers participating in a randomized trial of functional exercise training delivered by videoconferencing.

Adaptive Approaches to Exercise Rehabilitation for Postural Tachycardia Syndrome and Related Autonomic Disorders.

Exercise is a well-documented, nonpharmacologic treatment for individuals with autonomic dysfunction and associated orthostatic intolerance, such as postural tachycardia syndrome and related disorders. Exercise has been shown to increase blood volume, reverse cardiovascular deconditioning, and improve quality of life. Current first-line standard of care treatment for autonomic dysfunction combines graded approaches to exercise with medications and lifestyle modifications.

Psychosocial Support Needs and Preferences Among Family Caregivers of ICU Patients with Severe Acute Brain Injury: A Qualitative Thematic Analysis.

Background: Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative's ICU admission.

Reticulocyte Binding Protein Homologue 5 is a target of balancing selection in the population of Papua New Guinea.

Reticulocyte Binding Protein Homologue (RH5), a leading malaria vaccine candidate, is essential for erythrocyte invasion by the parasite, interacting with the human host receptor, basigin. RH5 has a small number of polymorphisms relative to other blood-stage antigens, and studies have shown that vaccine-induced antibodies raised against RH5 are strain-transcending, however most studies investigating RH5 diversity have been done in Africa. Understanding the genetic diversity and evolution of malaria antigens in other regions is important for their validation as vaccine candidates.

Derivation and validation of a clinical predictive model for longer duration diarrhea among pediatric patients in Kenya using machine learning algorithms.

Background: Despite the adverse health outcomes associated with longer duration diarrhea (LDD), there are currently no clinical decision tools for timely identification and better management of children with increased risk. This study utilizes machine learning (ML) to derive and validate a predictive model for LDD among children presenting with diarrhea to health facilities.

Methods: LDD was defined as a diarrhea episode lasting ≥ 7 days.

The polypharmacy combination of the BCL-2 inhibitor venetoclax (VEN) and the FLT3 inhibitor gilteritinib (GIL) is more active in acute myeloid leukemia cells than novel polypharmacologic BCL-2/FLT3 VEN-GIL hybrid single-molecule inhibitors.

Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel.

Preserving the Academic Mission Amid Radiologist Shortages and Financial Pressures.

Academic radiology practices are navigating unprecedented operational and financial challenges, including a growing radiologist shortage, escalating imaging volumes, and mounting financial pressures driven by rising salaries, increasing practice expenses, and declining reimbursements. To address these challenges, academic department leaders must prioritize securing enhanced hospital professional service agreements and renegotiating outpatient imaging agreements. These strategic initiatives are essential to sustaining academic missions and ensuring long-term success.

Using internet-assisted geocoding of 1940 census addresses to reconstruct enumeration districts for use with redlining and longitudinal health datasets.

Many historical administrative documents, such as the 1940 census, have been digitized and thus could be merged with geographic data. Merged data could reveal social determinants of health, health and social policy milieu, life course events, and selection effects otherwise masked in longitudinal datasets. However, most exact boundaries of 1940 census enumeration districts have not yet been georeferenced.

Blood Culture Use in Medical and Surgical Intensive Care Units and Wards.

Importance: Blood culture (BC) use benchmarks in US hospitals have not been defined.

Objective: To characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.

Design, Setting, And Participants: A retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted.

Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.

Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.

Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022.

Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.