Spatial analysis of human lung cancer reveals organized immune hubs enriched for stem-like CD8 T cells and associated with immunotherapy response.

The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially-localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens, and found that they were associated with beneficial responses to PD-1-blockade.

Combined PD-1, BRAF and MEK inhibition in BRAF colorectal cancer: a phase 2 trial.

While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAF colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAF CRC.

Impact of Continuous Flow Left Ventricular Assist Device on Heart Transplant Candidates: A Multi-State Survival Analysis.

(1) Objectives: The aim of this study was to investigate the impact of the prolonged use of continuous-flow left ventricular assist devices (LVADs) on heart transplant (HTx) candidates. (2) Methods: Between January 2012 and December 2019, we included all consecutive patients diagnosed with end-stage heart failure considered for HTx at our institution, who were also eligible for LVAD therapy as a bridge to transplant (BTT). Patients were divided into two groups: those who received an LVAD as BTT (LVAD group) and those who were listed without durable support (No-LVAD group).

Carpentier-Edwards Magna Ease bioprosthesis: a multicentre clinical experience and 12-year durability.

Objectives: The goal of this multicentre retrospective study was to compare long-term clinical and haemodynamic outcomes of the Carpentier-Edwards Magna Ease (CEME) bioprosthesis by patient age.

Methods: We included consecutive patients who underwent isolated and combined surgical aortic valve replacement (AVR) with CEME valve between January 2008 and March 2020 at 4 cardiac surgery centres in Italy. Survival distribution was evaluated at follow-up according to age and surgery type (combined or isolated AVR), together with freedom from structural valve deterioration (SVD), reoperation and combined events, i.

Spatially organized multicellular immune hubs in human colorectal cancer.

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors.

Unilateral versus bilateral cerebral perfusion during aortic surgery for acute type A aortic dissection: a multicentre study.

Objectives: The aim of this retrospective multicentre study was to investigate and compare clinical outcomes of unilateral and bilateral antegrade cerebral perfusion (ACP) strategies on cerebral protection during surgery for type A aortic dissection.

Methods: Data from 646 patients who underwent surgical repair of thoracic type A aortic dissection using unilateral and bilateral ACP with moderate hypothermic circulatory arrest in 3 cardiac surgical institutions between 2008 and 2018 were analysed. Propensity matching was performed to assess which technique ensured better outcomes.

COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak.

Objectives: The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy.

Background: The worldwide severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has created unprecedented challenges for public health, demanding exceptional efforts for the successful management and treatment of affected patients. Heart transplant patients represent a unique cohort of chronically immunosuppressed subjects in which SARS-CoV-2 may stimulate an unpredictable clinical course of infection.

Recurrent autoimmune myocarditis in a young woman during the coronavirus disease 2019 pandemic.

We report a unique case of a young woman with recurrent immune-mediated (virus-negative) lymphocytic fulminant myocarditis during the coronavirus disease 2019 pandemic. At the first endomyocardial biopsy (EMB)-proven episode, she had concomitant pneumonia, and a temporary biventricular assist device implant was followed by complete and long-lasting cardiac recovery. Five years later, she was re-admitted for relapsing cardiogenic shock with a recent history of pneumonia.

TAVR, SAVR and MI-AVR. Good Things Come to Those Who Wait.

Modern medicine uses a combination of advanced technology and established knowledge to reach its ultimate goal: healing patients while limiting risks and preventing disease [...

Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience.

Objectives: Few anecdotal cases have been reported in the literature regarding heart transplant recipients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report our experience with 6 patients hospitalized in Northern Italy during the outbreak.

Methods: Of the 396 living heart transplant recipients from 1985 to 2020 included in the study, 6 patients developed the novel 2019 coronavirus disease.

Cotargeting among microRNAs in the brain.

MicroRNAs (miRNAs) play roles in diverse developmental and disease processes. Distinct miRNAs have hundreds to thousands of conserved mRNA binding sites but typically direct only modest repression via single sites. Cotargeting of individual mRNAs by different miRNAs could potentially achieve stronger and more complex patterns of repression.