Real-world implementation of non-endoscopic triage testing for Barrett's oesophagus during COVID-19.

BACKGROUND: The Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett's oesophagus surveillance. AIMS: (i) To review reflux referral patterns and Barrett's surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services. DESIGN AND METHODS: Cytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included. RESULTS: A total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N = 9784/10 577) were sufficient for analysis. In the reflux cohort (N = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett's surveillance (N = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33-1.41, P < 0.001)). Some surveillance referrals (21.5%, N = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N = 225/5630) for p53 and 7.6% (N = 430/5694) for atypia), increasing to 11.8% (N = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N = 58/294) in ultra-long segments. CONCLUSIONS: Cytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett's oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts.

Effect of platelet-activating factor on human polymorphonuclear leukocyte enhancement of chemiluminescence and antibody-dependent cellular cytotoxicity.

The effect of platelet-activating factor on human granulocytes was determined by luminol-dependent chemiluminescence (CL), antibody-dependent cellular cytotoxicity (ADCC), and rosette assay. An activation of the respiratory burst could be measured by CL and be shown to depend on the presence of extracellular calcium. This direct stimulation of PMN was proved to be inhibited by oxygen radical scavengers as well as by the calcium channel blocker diltiazem. Furthermore, the presence of PAF enhanced the activation of PMN via Fc- or C3b-receptors, as demonstrated by CL and ADCC. On the other hand, no influence on the rosette-forming capacity of PMN could be detected. The results support the concept of the import role of PAF in inflammatory processes.

The role of antibody and complement in the cellular response to Trypanosoma congolense.

The in vitro cytotoxic response of bovine granulocytes and monocytes and of murine peritoneal macrophages against Trypanosoma congolense in the presence of antibody, antibody plus complement or complement alone was assessed using luminol aided chemiluminescence as a second parameter for effector cell activation. Neither cell type exhibited any trypanolysis exceeding that of antibodies and complement alone. The kinetics of the chemiluminescence response in the course of these reactions closely correlated with the trypanocidal activity of the antibody preparation used, suggesting effector cell activation as a response to antibody-mediated immobilization and damage of the trypanosomes. From these results and electron microscopic investigations we conclude that antibody- or complement-dependent cell-mediated cytotoxic reactions do not play a significant role in the defence of T. congolense infection, neither by extracellular lysis nor killing of ingested parasites.

Cellular response and resistance to the primary infection of rats and mice with Nematospiroides dubius.

LEWIS rats, in contrast to NMRI mice, have been found to be resistant to an oral infection with Nematospiroides dubius (Baylis, 1926). Comparative studies of the peritoneal response to infection showed a strong increase in the cell number predominantly of eosinophilic and neutrophilic granulocytes in rats, whereas in mice only a weak reaction occurred. As shown by the chemiluminescence response to either antibody--or complement-coated larvae, the granulocyte reaction caused an increased production of toxic oxygen species by the peritoneal cells. Purified granulocytes from rats or mice showed about a ten-fold higher oxidant generation than macrophages. The higher metabolic activity of granulocytes of either species resulted in rapid and strong killing of antibody or complement-coated infective larvae by granulocytes of either species, whereas macrophages failed to express a significant larvicidal potency. From these results we concluded that the activated oxygen species derived from the metabolic burst of granulocytes are essential for an effective control of the primary infection with N. dubius. This suggests that the rapid and strong granulocyte response may form the basis of the resistance in rats. Thus, in mice, the ability of N. dubius to prevent the granulocyte response may serve as an escape mechanism of the parasite.

Relationship between histocompatibility antigens, other surface determinants and the IgE receptor on rat mast cells.

Rat alloantibodies recognizing classical transplantation antigens (CTA) or non-H-1 determinants were able to compete effectively with monomeric IgE or IgG-coated sheep erythrocytes for receptor sites on the rat mast cell surface. Inhibitory capacity, however, was entirely confined to anti-CTA antibodies of the IgG2a subclass, whereas IgG1 antibodies lacked this ability. Analogously, F(ab')2 fragments of anti-CTA antibody consistently failed to affect IgE binding, but exposure of cell-bound F(ab')2 to anti-rat IgG restored its inhibitory capacity. From these results it was concluded that receptor sites recognizing the Fc portion of the anti-CTA molecule are involved in the inhibition process. Based on a cytotoxicity assay and on comparative absorption studies on alloantisera, the existence and relative amount of CTA and I region-associated antigens on purified rat mast cells and lymph node cells were analyzed. Whereas the CTA concentration per unit surface area on both cell types was very similar, rat mast cells consistently lacked Ia antigens.