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Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain—an index of neuronal damage—were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P, Sol et al. report that in case–control approaches, plasma lipidomic profile is richer in differences than CSF. Interestingly, patients with faster progression show decreased plasmatic triacylglycerides and phospholipids, compatible with hypermetabolism. They conclude that the plasma lipidomic profile holds promise for patient stratification., Graphical Abstract Graphical Abstract

Background The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE 50% reduction in glomerular filtrate rate or end-stage renal disease. Results Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P = 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with 50% had poorer renal function compared with the other groups. Conclusions We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research.

Background It remains unknown to what extent consensus molecular subtype (CMS) groups and immune-stromal infiltration patterns improve our ability to predict outcomes over tumor–node–metastasis (TNM) staging and microsatellite instability (MSI) status in early-stage colorectal cancer (CRC). Patients and methods We carried out a comprehensive retrospective biomarker analysis of prognostic markers in adjuvant chemotherapy-untreated (N = 1656) and treated (N = 980), stage II (N = 1799) and III (N = 837) CRCs. We defined CMS scores and estimated CD8+ cytotoxic lymphocytes (CytoLym) and cancer-associated fibroblasts (CAF) infiltration scores from bulk tumor tissue transcriptomes (CMSclassifier and MCPcounter R packages); constructed a stratified multivariable Cox model for disease-free survival (DFS); and calculated the relative proportion of explained variation by each marker (clinicopathological [ClinPath], genomics [Gen: MSI, BRAF and KRAS mutations], CMS scores [CMS] and microenvironment cells [MicroCells: CytoLym+CAF]). Results In multivariable models, only ClinPath and MicroCells remained significant prognostic factors, with both CytoLym and CAF infiltration scores improving survival prediction beyond other markers. The explained variation for DFS models of ClinPath, MicroCells, Gen markers and CMS4 scores was 77%, 14%, 5.3% and 3.7%, respectively, in stage II; and 55.9%, 35.1%, 4.1% and 0.9%, respectively, in stage III. Patients whose tumors were CytoLym high/CAF low had better DFS than other strata [HR=0.71 (0.6–0.9); P = 0.004]. Microsatellite stable tumors had the strongest signal for improved outcomes with CytoLym high scores (interaction P = 0.04) and the poor prognosis linked to high CAF scores was limited to stage III disease (interaction P = 0.04). Conclusions Our results confirm that tumor microenvironment infiltration patterns represent potent determinants of the risk for distant dissemination in early-stage CRC. Multivariable models suggest that the prognostic value of MSI and CMS groups is largely explained by CytoLym and CAF infiltration patterns.