The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab... Show moreThe CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI − 0.33 to − 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (− 0.01 (95% CI − 0.01 to − 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded. Show less
BackgroundIn rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and... Show moreBackgroundIn rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment.MethodsThis registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality.ResultsA total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI.ConclusionOncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment. Show less
Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single... Show moreHeterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced 56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lung TECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECs putatively regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECs were most sensitive to vascular endothelial growth factor blockade. Only tip TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen modification as a candidate angiogenic pathway. Show less
