Association of Coronary Computed Tomography-Defined Myocardial Bridge With Pre- and Post-Procedural Fractional Flow Reserve in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Myocardial bridge (MB) is a common coronary anomaly characterized by a tunneled course through the myocardium. Coronary computed tomography angiography (CCTA) can identify MB. The impact of MB detected by CCTA on coronary physiological parameters before and after percutaneous coronary intervention (PCI) is unknown.Methods and Results: We investigated 141 consecutive patients who underwent pre-PCI CCTA and fractional flow reserve (FFR)-guided elective PCI for de novo single proximal lesions in the left anterior descending artery (LAD). We compared clinical demographics and physiological parameters between patients with and without CCTA-defined MB. MB was identified in 46 (32.6%) patients using pre-PCI CCTA. The prevalence of diabetes was higher among patients with MB. Median post-PCI FFR values were significantly lower among patients with than without MB (0.82 [interquartile range 0.79-0.85] vs. 0.85 [interquartile range 0.82-0.89]; P=0.003), whereas pre-PCI FFR values were similar between the 2 groups. Multivariable linear regression analysis revealed that the presence of MB and greater left ventricular mass volume in the LAD territory were independently associated with lower post-PCI FFR values. Multivariable logistic regression analysis also revealed that the presence of MB and lower pre-PCI FFR values were independent predictors of post-PCI FFR values ≤0.80. CONCLUSIONS: CCTA-defined MB independently predicted both lower post-PCI FFR as a continuous variable and ischemic FFR as a categorical variable in patients undergoing elective PCI for LAD.

Immune-based therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death. The immune-rich contexture of the HCC microenvironment makes this tumour an appealing target for immune-based therapies. Here, we discuss how the functional characteristics of the liver microenvironment can potentially be harnessed for the treatment of HCC. We will review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area.

Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer.

Importance: Gut dysbiosis impairs response to immune checkpoint inhibitors (ICIs) and can be caused by broad-spectrum antibiotic (ATB) therapy. Objective: To evaluate whether there is an association between ATB therapy administered concurrently (cATB) or prior (pATB) to ICI therapy and overall survival (OS) and treatment response to ICI therapy in patients with cancer treated with ICIs in routine clinical practice. Design, Setting, and Participants: This prospective, multicenter, cohort study conducted at 2 tertiary academic referral centers recruited 196 patients with cancer who received ICI therapy between January 1, 2015, and April 1, 2018, in routine clinical practice rather than clinical trials. Main Outcomes and Measures: Overall survival calculated from the time of ICI therapy commencement and radiologic response to ICI treatment defined using the Response Evaluation Criteria in Solid Tumors (version 1.1), with disease refractory to ICI therapy defined as progressive disease 6 to 8 weeks after the first ICI dose without evidence of pseudoprogression. Results: Among 196 patients (137 men and 59 women; median [range] age, 68 [27-93] years) with non-small cell lung cancer (n = 119), melanoma (n = 38), and other tumor types (n = 39), pATB therapy (HR, 7.4; 95% CI, 4.3-12.8; P < .001), but not cATB therapy (HR, 0.9; 95% CI, 0.5-1.4; P = .76), was associated with worse OS (2 vs 26 months for pATB therapy vs no pATB therapy, respectively) (hazard ratio [HR], 7.4; 95% CI, 4.2-12.9) and a higher likelihood of primary disease refractory to ICI therapy (21 of 26 [81%] vs 66 of 151 [44%], P < .001). Overall survival in patients with non-small cell lung cancer (2.5 vs 26 months, P < .001), melanoma (3.9 vs 14 months, P < .001), and other tumor types (1.1 vs 11, P < .001) was consistently worse in those who received pATBs vs those who did not. Multivariate analyses confirmed that pATB therapy (HR, 3.4; 95% CI, 1.9-6.1; P < .001) and response to ICI therapy (HR, 8.2; 95% CI, 4.0-16.9; P < .001) were associated with OS independent of tumor site, disease burden, and performance status. Conclusions and Relevance: Despite being limited by sample size, geographic origin, and the lack of correlative analyses on patients' gut microbiota, this study suggests that pATB therapy but not cATB therapy is associated with a worse treatment response and OS in unselected patients treated with ICIs in routine clinical practice. Mechanistic studies are urgently required to investigate ATB-mediated alterations of gut microbiota as a determinant of poorer outcome following ICI treatment.