Citations

Abstract BACKGROUND Historically the success of mass spectrometry in the clinical laboratory has focused on drugs of abuse confirmations, newborn screening, and steroid analysis. Clinical applications of mass spectrometry continue to expand, and mass spectrometry is now being used in almost all areas of laboratory medicine. CONTENT A brief background of the evolution of mass spectrometry in the clinical laboratory is provided with a discussion of future applications. Prominent examples of mass spectrometry are covered to illustrate how it has improved the practice of medicine and enabled physicians to provide better patient care. With increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing has been shown to provide cost-effective solutions. In addition to pointing out the numerous benefits, the challenges of implementing mass spectrometry in the clinical laboratory are also covered. SUMMARY Mass spectrometry continues to play a prominent role in the field of laboratory medicine. The advancement of this technology along with the development of new applications will only accelerate the incorporation of mass spectrometry into more areas of medicine.

Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation. In this study we report that Notch recycling to the cell surface is dependent on the COMMD–CCDC22–CCDC93 (CCC) complex, a recently identified regulator of endosomal trafficking. Disruption in this system leads to intracellular accumulation of Notch2 and concomitant reduction in Notch signaling. Interestingly, among the 10 copper metabolism MURR1 domain containing (COMMD) family members that can associate with the CCC complex, only COMMD9 and its binding partner, COMMD5, have substantial effects on Notch. Furthermore, Commd9 deletion in mice leads to embryonic lethality and complex cardiovascular alterations that bear hallmarks of Notch deficiency. Altogether, these studies highlight that the CCC complex controls Notch activation by modulating its intracellular trafficking and demonstrate cargo-specific effects for members of the COMMD protein family.

SummaryBackgroundReliable tools for patient selection are critical for clinical drug trials.AimTo evaluate a consensus‐based, standardised magnetic resonance enterography (MRE) protocol for selecting patients for inclusion in Crohn's disease (CD) multicenter clinical trials.MethodsThis study recruited 20 patients [Crohn's Disease Activity Index (CDAI) scores: <150 (n = 8); 150–220 (n = 4); 220–450 (n = 8)], to undergo ileocolonoscopy and two MREs (with and without colonic contrast) within a 14‐day period. Procedures were scored centrally using, Magnetic Resonance Index of Activity (MaRIA), and both Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic Score (SES‐CD).Results37 MREs were acquired. Both MREs were evaluable in 16 patients for calculation of test–retest and inter‐reader reliability scores. The MaRIA scores for the terminal ileum had excellent test–retest and inter‐reader reliability, with correlations >0.9. The proximal ileum showed strong within‐reader agreement (0.90–0.96), and fair between‐reader agreement (0.59–0.72). MRE procedures were tolerable. MaRIA scores correlated with CDEIS and SES‐CD (0.63 and 0.71), but not with CDAI (0.34). MRE identified 3 patients with intra‐abdominal complications, who would otherwise have been included in clinical trials. Furthermore, both MRE and ileocolonoscopy identified active bowel wall inflammation in 2 patients with CDAI <150, and none in 1 patient with CDAI > 220. Data quality was good/excellent in 85% of scans, and fair or better in 96%.ConclusionsMagnetic resonance enterography of high‐quality and reproducibility was feasible in a global multi‐ centre setting, with evidence for improved selectivity over CDAI and ileocolonoscopy in identifying appropriate CD patients for inclusion in therapeutic intervention trials.