Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours.

Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics1. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH2. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell-cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.

Effectiveness of intra-venous steroids for preventing surgery for lumbo-sacral radiculopathy secondary to intervertebral disc herniation: a retrospective study of 213 patients.

The natural history of lumbar disc herniation with radiculopathy is favorable, with 95% of patients expected to be pain-free within 6 months of onset. Despite the favorable prognosis, operative treatment is often chosen by patients unable to "ride out" the radicular episode. Prospective studies comparing surgical with non-surgical treatment have demonstrated similar long-term results. We conducted a retrospective case-series study of patients with a lumbar disc herniation and intractable radicular pain without significant neurological deficits treated with intra-venous dexamethasone. The primary outcome measure was whether the patient had undergone operative treatment within 1 year of receiving the intravenous steroid treatment. 213 patients met our inclusion criteria. 30 were lost to follow-up and 2 had died before completing 1 year of follow-up. Of the remaining 181 patients, 133 (73.48%) had not undergone surgery within 1 year of receiving intra-venous steroid treatment while 48 (26.51%) had undergone surgery. 6 (3.31%) of the patients had undergone surgery more than 1 year of receiving IV steroid treatment. Intravenous steroid treatment in our retrospective series was approximately 30% better at preventing the need for surgery than the reported outcomes of conservative treatment in randomized controlled trials previously published.