Search

Purpose: Primarily, to evaluate the repeatability and reproducibility of the new noncontact esthesiometer (NCE) in healthy subjects. Secondarily, the corneal sensitivity threshold measurements of the NCE were compared with those of the Cochet-Bonnet esthesiometer (CBE)., Design: Assessment reliability study., Methods: Two examiners measured bilateral corneal sensitivity thresholds by NCE and CBE. Triple NCE measurements were performed per eye at all 5 levels, whereas single CBE measurements were performed per eye. When appropriate, NCE (mBar) and CBE (mm) measurements were converted to millinewtons (mN) for direct comparison between devices. The NCE measurement variations were calculated with the intra-class correlation coefficients (ICC) for the primary objective. For the secondary objective, Bland-Altman plots with 95% limits of agreement (95%-LoA) and Spearman's rank correlation coefficients were used to evaluate the level of agreement and linear relationship between the corneal sensitivity thresholds obtained with both devices. Generalized estimating equation models were used to account for the inter-eye correlation of the same study participant., Results: Fifty subjects (100 eyes) aged 29 years (median) were included. There were no statistically significant differences in the pressure measured by both observers at each NCE level (all P > .05). There was a high intra-observer and inter-observer repeatability of the NCE measurements (ICC > 0.90) and a strong linear correlation (rho > 0.7) at each NCE level. The difference between the mean corneal sensitivity thresholds (mN) measured with the NCE (0.052 ± 0.021 mN) and CBE (0.046 ± 0.005 mN) was statistically significant (P = .001). Bland-Altman analysis revealed a differential bias of +0.00578 mN (95%-LoA -0.03677 - +0.04833 mN) between threshold measurements., Conclusions: The NCE provides reliable user-independent corneal sensitivity measurements. The NCE and CBE do not yield similar values. Thus, both devices cannot be used interchangeably., (Copyright © 2024. Published by Elsevier Inc.)

The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor 25 (TNFRSF25) and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively, was used to pretreat recipient mice prior to allogeneic-HSCT (aHSCT). Pretreatment induced Treg expansion persisting early post-aHSCT leading to diminished GVHD and improved transplant outcomes. Expansion was accompanied by an increase in frequency of stable and functionally active Tregs as evidenced by in vitro assays using cells from major GVHD target tissues including colon, liver, and eye. Importantly, pretreatment supported epithelial cell function/integrity, a diverse microbiome including reduction of pathologic bacteria overgrowth and promotion of butyrate producing bacteria, while maintaining physiologic levels of obligate/facultative anaerobes. Notably, using a sphingosine 1-phosphate receptor agonist to sequester T cells in lymphoid tissues, we found that the increased tissue Treg frequency included resident CD69 + CD103 + FoxP3 + hepatic Tregs. In contrast to infusion of donor Treg cells, the strategy developed here resulted in the presence of immunosuppressive target tissue environments in the recipient prior to the receipt of donor allo-reactive T cells and successful perseveration of GVL responses. We posit strategies that circumvent the need of producing large numbers of ex-vivo manipulated Tregs, may be accomplished through in vivo recipient Treg expansion, providing translational approaches to improve aHSCT outcomes.

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) of the colon is rare with a poor prognosis. Since the first description of a mixed neoplasm 100 years ago, the nomenclature has evolved, most recently with the 2022 World Health Organization (WHO) classification system. We describe our experience of a case of locoregionally advanced MiNEN of the descending colon treated with curative laparoscopic resection and adjuvant chemotherapy. The patient is a 72 year old woman who presented with haematochezia. Initial clinical diagnosis was poorly differentiated adenocarcinoma of the descending colon, cT2N0M0, cStage I. Laparoscopic partial colectomy of the descending colon with D3 lymph node dissection and intracorporeal overlap anastomosis was performed. The pathological diagnosis however, returned mixed adenocarcinoma-neuroendocrine carcinoma (MANEC) of the descending colon, pT4aN1bM0, pStage IIIB, a subgroup of MiNEN: 70% was neuroendocrine carcinoma (NEC), whilst poorly differentiated mucinous carcinoma constituted 30% of the tumour. She completed 4 courses of irinotecan plus cisplatin (IP) adjuvant chemotherapy and is currently recurrence-free at postoperative year 2. The clinical course of MiNEN depends on the biology of the two components, both of which must be pathologically characterised. Even quantitatively discrete components should be carefully subtyped as their prognostic relevance is undetermined., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Human and animal rights: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: For this type of study, formal consent is not required., (© 2025. Japanese Society of Gastroenterology.)