Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

Immunomodulating versus high-protein oral preoperative supplement in surgical patients - A two-center, prospective, randomized clinical trial.

OBJECTIVES: For many years, immunonutrition was believed to reduce postoperative complications in patients undergoing major abdominal surgery. However, recent studies questioned that belief. Moreover, the perioperative intake of proteins has gained more and more attention and has shown clinical value. Therefore, the aim of this study was to compare the clinical effect of immunomodulating (IM) plus high-protein (HP) and pure HP supplements during the preoperative period. METHODS: Between January 2011 and December 2020, 299 well-nourished patients (130 female and 169 male; mean age: 60.8 y) undergoing major abdominal surgery at two surgical centers were randomized to receive either preoperative IM or HP oral supplements for 7 d after surgery. In all patients, an enhanced recovery after surgery protocol was applied. Outcome measures of the intend-to-treat analysis were number and type of complications, length of hospitalization, and mortality. RESULTS: Both groups were comparable in terms of age, sex, and type of surgery. The median length of postoperative hospital stay was 8 d (range, 6-12 d) in the IM group and 7 d (range, 6-10 d) in the HP group (P = 0.153). Postoperative complications were observed in 29 patients (21.3%) in the IM group and 28 (17.8%) in the HP group (P = 0.442) The risk of readmission was comparable (5.1% vs 4.9%; P = 0.924) for IM and HP supplements, respectively. Postoperative nausea and vomiting occurred in 21 patients in the IM group (15.4%) and 17 patients in the HP group (10.4%; P = 0.195). No difference in gastrointestinal function evaluated with time to first flatus was observed (P = 0.272) CONCLUSIONS: The study demonstrated no difference between preoperative IM + HP and HP supplements in surgical patients. Therefore, the routine preoperative use of IM supplements in all surgical patients cannot be recommended.

Enhanced Recovery after Surgery (ERAS) Protocol Is a Safe and Effective Approach in Patients with Gastrointestinal Fistulas Undergoing Reconstruction: Results from a Prospective Study.

BACKGROUND AND AIMS: An enterocutaneous fistula (ECF) poses a major surgical problem. The definitive surgical repair of persistent fistulas remains a surgical challenge with a high rate of re-fistulation and mortality, and the reasons for that is not the surgical technique alone. Enhanced Recovery after Surgery (ERAS®) is an evidence-based multimodal perioperative protocol proven to reduce postoperative complications. The aim of the study was to assess the clinical value of the ERAS protocol in surgical patients with ECF. METHODS: ERAS protocol was used in all patients scheduled for surgery for ECF at the Stanley Dudrick's Memorial Hospital in Skawina between 2011 and 2020. A multidisciplinary team (MDT) was in charge of the program and performed annual audits. A consecutive series of 100 ECF patients (44 females, 56 males, mean age 54.1 years) were evaluated. Postoperative complications rate, readmission rate, length of hospital stay, prevalence of postoperative nausea and vomiting were assessed. Registered under ClinicalTrials.gov Identifier no. NCT04771832. RESULTS: ERAS protocol was successfully introduced for ECF surgeries; however, eight modifications to the ERAS program was performed in 2015. They led to improvement of surgical outcomes: reduction of postoperative nausea and vomiting (15 vs. 17% patients, p = 0.025), overall complication rate (11 vs. 10, p = 0.021), median length of hospital stay (overall and after surgery, p = 0.022 and 0.002, respectively). CONCLUSIONS: ERAS protocol can be successfully used for ECF patients. Prescheduled audits can contribute to the improvement of care.

Rectovaginal fistula after gastrointestinal tract continuity restoration using a stapler--case report.

The authors presented a case of rectovaginal fistula in a 40-year old female patient after gastrointestinal tract continuity restoration (Hartmann's operation) performed because of iatrogenic rectal damage. The most likely cause of rectovaginal fistula development was the erroneous introduction of the stapler into the vagina and sigmoidovaginostomy during an attempt to reconstruct the continuity of the gastrointestinal tract. In order to reconstruct the continuity of the gastrointestinal tract the patient was subject to anterior rectal resection, sigmoidorectostomy, and closure of the fistula inside the vaginal wall by its duplication. Additionally, a double protective ileostomy was performed, which was subject to closure after three months.