SUMMARY We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

In a large cohort referred for invasive hemodynamic assessment, PH-HFpEF was common. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient are all associated with mortality and cardiac hospitalizations.

No abstract

Multidrug-resistant bacteria pose a serious health threat, especially in hospitals. Horizontal gene transfer (HGT) of mobile genetic elements (MGEs) facilitates the spread of antibiotic resistance, virulence, and environmental persistence genes between nosocomial pathogens. We screened the genomes of 2173 bacterial isolates from healthcare-associated infections from a single hospital over 18 months, and identified identical nucleotide regions in bacteria belonging to distinct genera. To further resolve these shared sequences, we performed long-read sequencing on a subset of isolates and generated highly contiguous genomes. We then tracked the appearance of ten different plasmids in all 2173 genomes, and found evidence of plasmid transfer independent from bacterial transmission. Finally, we identified two instances of likely plasmid transfer within individual patients, including one plasmid that likely transferred to a second patient. This work expands our understanding of HGT in healthcare settings, and can inform efforts to limit the spread of drug-resistant pathogens in hospitals.