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Background & Aims-Esophageal adenocarcinomas (EAC) are heterogeneous and often preceded by Barrett's esophagus (BE). Many genomic changes have been associated with development of BE and EAC, but little is known about epigenetic alterations. We performed *

Background Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. Methods CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. Results An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. Conclusion CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.

Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori-associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies.