Goran Madzarac

Background/Objectives: This 7-day rat tracheocutaneous fistula study considered the not-studied issues of tracheocutaneous fistula course, wound healing, and fistula in the NO-system relations. Therefore, we focused on fistulas’ severe course, tracheocutaneous fistula → air leak → compensatory diaphragmatic/abdominal “heaving”, NO-system failed relations, and therapy resolution. Stable gastric pentadecapeptide BPC 157 was proposed. Methods: Tracheocutaneous fistula rats received daily medication (/kg), alone or combined, BPC 157 therapy (10 µg, 10 ng, in drinking water or intraperitoneally) along with a triple NO-agent approach (L-NAME 5 mg, L-arginine 100 mg, and L-NAME+L-arginine, intraperitoneally). Results: Tracheocutaneous fistulas occurred as specific and NO-system-related as follows: NO system: blockade (L-NAME-aggravation) over-activity (L-arginine-amelioration) or immobilization (L-NAME+L-arginine oppose each other’s effects). Controls presented severe clinical signs of respiratory distress, failed healing, skin and tracheal defects, a not-healed and open, macro/microscopically, and fistulous tract that was well-formed and wide, tracheal shrinking below the fistula, and clinically, open-mouth breathing, “heaving abdomen”, cyanosis (bluish snout, ears, extremities), abundant secretion through the fistula, and weight loss. Fistula tissue NO level decreased, and the malondialdehyde (MDA) level increased. The BPC 157 therapy (both application routes) resulted in rapid recovery. Healing of defects (skin and trachea) and fistula closure, macro/microscopically, corresponded with clinical findings, avoiding observable clinical signs of dyspnea, reducing weight loss, and avoiding any sign of “heaving abdomen”. BPC 157-treated rats displayed regular breathing movements without observable signs of respiratory distress. Finally, when combined, BPC 157 therapy upgrades L-arginine amelioration, abolishes L-NAME-induced worsening, and restores full healing after NO immobilization (L-NAME+L-arginine). BPC 157 counteracted increase in NO level and counteracted increase in MDA level. Conclusions: Thus, first, acting systemically, BPC 157 reverses tracheocutaneous fistula course in rats. It acts through the NO system.

Background/Objectives: The use of intraoperative venoarterial extracorporeal life support (VA ECLS) has traditionally been used to support unstable patients undergoing complex lung transplantation. More evidence is emerging that the use of intraoperative VA ECLS may be beneficial for all patients undergoing lung transplantation. The aim of this study was to report the safety and feasibility of lung transplantation with the routine use of central VA ECLS. Methods: In this single-center retrospective observational study, all consecutive patients undergoing lung transplantation from April 2021 until September 2025 were included. Early outcomes and the incidence of primary graft dysfunction were evaluated with the International Society for Heart and Lung Transplantation criteria at 72 h after transplantation. Survival and chronic lung allograft dysfunction (CLAD)-free survival were reported with Kaplan–Meier estimates and 95% confidence intervals (CIs). Results: During the study period, 35 patients were successfully transplanted with the aid of central VA ECLS. There were no complications associated with intraoperative ECLS. One revision surgery was performed for immediate postoperative bleeding, and one for bronchial anastomosis air leak. Operative mortality occurred in three patients (8.6%). The median in-hospital stay was 30 (25–43) days. Severe primary graft dysfunction at 72 h was observed in four (11.4%) patients. Survival and CLAD-free survival at 1-, 3-, and 5-years following surgery were 85% (95% CI [74–98]), 74% (95% CI [59–92]), 67% (95% CI [28–82]), and 82% (95% CI [70–96]), 52% (95% CI [37–74]), 36% (95% CI [11–59]), respectively. Conclusions: Lung transplantation can safely be performed with the aid of central VA ECLS, with a low rate of primary graft dysfunction and favorable long-term outcomes. Further follow-up studies and greater experience are needed to make inferences on the long-term outcomes. This technique is relatively recent and evolving, representing an innovative intersection of advanced supportive technology with transplant surgery, potentially broadening indications and improving success rates.