Validation of a French Version of the Visual Function and Corneal Health Status Instrument and Correlation With Vision and Glare Measurements in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To validate a French version of the Visual Function and Corneal Health Status (V-FUCHS) instrument in Fuchs endothelial corneal dystrophy (FECD) and to correlate questionnaire scores with objective measurements of best-corrected visual acuity (BCVA) and intraocular straylight. METHODS: The original V-FUCHS 15-item instrument was designed to assess VA and glare in patients with FECD. It was translated from English to French and back translated to English by independent translators. The questionnaire was administered on 2 occasions (4 weeks apart), and BCVA, modified Krachmer grade, and straylight were measured. Construct validity, internal consistency, test-retest reliability, and predictive validity were assessed. RESULTS: A total of 159 subjects, aged 41 to 86 years, were prospectively recruited from July 2019 to October 2020 and classified into 6 groups: mild, moderate, or advanced FECD; unilateral or bilateral Descemet membrane endothelial keratoplasty for FECD; and healthy controls (n = 35). Construct validity was confirmed by item response theory model. Cronbach alpha demonstrated excellent internal consistency (VA: 0.91, glare: 0.88), and intraclass correlations showed good test-retest reliability (VA: 0.75 and glare: 0.82). Significant correlations were observed between both VA and glare factors and the modified Krachmer grade, BCVA, and straylight. CONCLUSIONS: The proposed French version of the V-FUCHS instrument provides a valid and reliable tool for the assessment of visual disability in patients with FECD. This questionnaire bridges the gap between self-reported FECD symptoms and objective clinical measurements, which may prove useful to optimize the timing of surgery and to assess postoperative improvement in symptoms.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.