Trends in HeartMate 3: What we know so far.

BACKGROUND: The HeartMate 3 left ventricular assist device (LVAD) is a novel, intrapericardial, centrifugal-flow pump with a fully magnetically-levitated rotor designed to provide hemodynamic support in patients with end-stage heart failure. Unique aspects of this LVAD have allowed for improved hemocompatibility and the development of minimally-invasive implantation techniques. METHODS: The PubMed, EMBASE, and Google Scholar databases were searched for publications relating to the HeartMate 3 device, with a focus on hemocompatibility related outcomes, anticoagulation management, and surgical techniques. RESULTS: Nine articles analyzing hemocompatibility related outcomes from two clinical trials, two clinical studies, and one registry series were identified. CONCLUSION: HeartMate 3 has reduced the rate of disabling stroke and pump thrombosis. However, despite increased hemocompatibility due to specialized design features, the residual risk of both surgical, and gastrointestinal bleeding remains a major adverse outcome. Different anticoagulation management and surgical techniques have been evaluated to address the remaining complications.

Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor-immune hubs.

Spatially resolved gene expression profiling provides insight into tissue organization and cell-cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC.

Deep generative model deciphers derailed trajectories in acute myeloid leukemia.

Single-cell genomics has the potential to map cell states and their dynamics in an unbiased way in response to perturbations like disease. However, elucidating the cell-state transitions from healthy to disease requires analyzing data from perturbed samples jointly with unperturbed reference samples. Existing methods for integrating and jointly visualizing single-cell datasets from distinct contexts tend to remove key biological differences or do not correctly harmonize shared mechanisms. We present Decipher, a model that combines variational autoencoders with deep exponential families to reconstruct derailed trajectories (https://github.com/azizilab/decipher). Decipher jointly represents normal and perturbed single-cell RNA-seq datasets, revealing shared and disrupted dynamics. It further introduces a novel approach to visualize data, without the need for methods such as UMAP or TSNE. We demonstrate Decipher on data from acute myeloid leukemia patient bone marrow specimens, showing that it successfully characterizes the divergence from normal hematopoiesis and identifies transcriptional programs that become disrupted in each patient when they acquire NPM1 driver mutations.

Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens.

Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented resolution1-11. However, broad clinical application of these methods remains challenging, due to several practical and preanalytical challenges that are incompatible with typical clinical care workflows, namely the need for relatively large, fresh tissue inputs. In the present study, we show that multimodal, single-nucleus (sn)RNA/T cell receptor (TCR) sequencing, spatial transcriptomics and whole-genome sequencing (WGS) are feasible from small, frozen tissues that approximate routinely collected clinical specimens (for example, core needle biopsies). Compared with data from sample-matched fresh tissue, we find a similar quality in the biological outputs of snRNA/TCR-seq data, while reducing artifactual signals and compositional biases introduced by fresh tissue processing. Profiling sequentially collected melanoma samples from a patient treated in the KEYNOTE-001 trial12, we resolved cellular, genomic, spatial and clonotype dynamics that represent molecular patterns of heterogeneous intralesional evolution during anti-programmed cell death protein 1 therapy. To demonstrate applicability to banked biospecimens of rare diseases13, we generated a single-cell atlas of uveal melanoma liver metastasis with matched WGS data. These results show that single-cell genomics from archival, clinical specimens is feasible and provides a framework for translating these methods more broadly to the clinical arena.

Lemierre's syndrome treated operatively.

Lemierre's syndrome (LS) is a pharyngeal infection complicated by infectious jugular vein thrombosis and septic emboli. Most commonly caused by Fusobacterium necrophorum, it may result in metastatic infection, especially when antibiotic treatment is delayed. Patients with LS are often healthy adults between 16 and 30 years who present with prolonged symptoms of pharyngitis, lateral neck pain, and fever. Other symptoms may include shortness of breath, tachycardia, and hypotension. When administered promptly, antibiotics can act as an effective treatment. However, complications may arise that require additional intervention. Herein, we report a case of LS in a young adult, complicated by severe pleural effusions that required surgical decortication.

Challenging Management of a Patient With Severe Bilateral Deep Vein Thrombosis.

Among patients with proximal iliofemoral deep vein thrombosis (DVT) and an elevated Villalta score, anticoagulation therapy alone may not be a sufficient management strategy in select cases. In this article, we report a case of severe bilateral iliofemoral DVT that resisted the standard treatment for DVT, requiring catheter-directed thrombolysis and subsequent mechanical thrombectomy.

A Newly Discovered Genetic Disorder Associated With Life-Threatening Aortic Disease in a 6-Year-Old Boy.

Aortic aneurysms in children are rare and when present are usually caused by a connective tissue disorder. In this article, we present a case of multiple aortic aneurysms in an adolescent with a novel finding of a gene variation that is associated with aortic disease.

Robotic Repair of a Congenital Isolated Cleft of Anterior Tricuspid Valve Leaflet.

Congenital isolated tricuspid valve (TV) cleft in the anterior leaflet is a rare occurrence, while clefts of the mitral valve leaflets are more common and are usually associated with other congenital heart diseases. In this article, we report a case of TV regurgitation in a young adult female due to an isolated congenital cleft in the anterior TV leaflet, which was surgically repaired using a minimally invasive robotic approach.