Beta Blocker

Limiting perioperative tachycardia (aiming for a heart rate \<90 beats per minute throughout the perioperative period) using the ultra-short acting beta-blocker landiolol in patients with cardiovascular risk factors undergoing major surgery might lower the incidence of perioperative myocardial injury. Feasibility of the intervention needs to be proven prior to conduction of a larger trial.

The goal of this prospective, single-center, multi-cohort clinical trial is to evaluate the efficacy and safety of neoadjuvant Iparomlimab/Tuvonralimab combined with CAPEOX, with or without propranolol, in patients with locally advanced pMMR (MSS) colon cancer. The main questions it aims to answer are: * What is the major pathological response (MPR) rate after neoadjuvant treatment and curative surgery (e.g., ≤10% viable tumor cells in the resected primary tumor)? * What are the key secondary outcomes (e.g., R0 resection rate, tumor regression grade, objective response rate, disease-free survival) and the safety/tolerability profile of these neoadjuvant regimens? If there is a comparison group: Researchers will compare Cohort A (Iparomlimab/Tuvonralimab + CAPEOX) versus Cohort B (Iparomlimab/Tuvonralimab + CAPEOX + propranolol) to see whether adding propranolol improves pathological and clinical responses while maintaining acceptable safety. Participants will: * Receive neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX for a protocol-defined number of cycles, with or without propranolol depending on cohort assignment. * Undergo curative-intent surgical resection after completing neoadjuvant therapy. * Be followed for postoperative treatment, adverse events, and longer-term outcomes (e.g., recurrence and survival), and may contribute tumor/blood samples for exploratory biomarker analyses related to treatment response.

Several data emphasize the relation between tachycardia (\>90/min) and high mortality during septic shock. The investigators previously demonstrated the high mortality associated with hypercontractility, tachycardia and the presence of a left ventricular obstruction. A severe hypovolemia, a hyper adrenergic stimulation or a severe vasoplegia can all explain this relation between tachycardia, hypercontractility and the mortality during septic shock. Landiolol is another short-term acting beta-blocker with a half-life of 4 minutes without any beta 2 activity or membrane stabilizing effect. The landiolol has been used in critically ill patients to control supraventricular tachycardia but not in this context of tachycardia and septic shock. The investigators hypothesize that landiolol by reducing the heart rate may improve the survival of patients treated for a septic shock and presenting with an hypercontractility state.