Role of NRF2 and reactive aldehydes in acute cellular rejection in liver transplant recipients.

OBJECTIVE: To evaluate the level of oxidative stress and antioxidative response in the transplanted liver and its role in acute cellular rejection (ACR). Particular attention was paid to ACR diagnosis in patients with hepatitis C (HCV), as histopathological features of ACR and viral disease recurrence overlap. METHODS: This retrospective study included 40 liver transplant patients who underwent liver transplantation with two consecutive liver biopsies performed during one hospitalization period: 1.) initial biopsy of the donor liver (before implantation) and 2.) indication biopsy (after suspected ACR). Based on the etiology, patients were divided into two groups: 22 patients with alcoholic liver cirrhosis (EtOH group) and 18 patients with hepatitis C cirrhosis (HCV group). We analyzed the presence of acrolein, HNE (4-hydroxynonenal), and the major antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) in both biopsies. RESULTS: The presence of acrolein and HNE in both biopsies indicates increased oxidative stress, while the decrease in these aldehydes in the indication biopsies indicates a decrease in oxidative stress over time, reflecting liver graft recovery. The absence of NRF2 in both biopsies reflects significantly reduced antioxidant protection in patients undergoing liver transplantation. CONCLUSION: The results support the role of oxidative stress in the pathogenesis of ACR. The presence of acrolein and the absence of HNE in the indication biopsy in patients with ACR could contribute to the diagnosis of ACR in clinical practice when functional antibodies are tested in the clinical setting.

Ventilator-Associated Pneumonia: Comparing Cadaveric Liver Transplant and Non-Transplant Surgical Patients

Ventilator-associated pneumonia is a frequent complication in intensive care surgical patients, particularly those with high severity scores on admission. We studied the incidence and clinical outcome of ventilator-associated pneumonia among patients undergoing major general surgery procedures and those undergoing cadaveric liver transplantation in our hospital. Patients with the intensive care unit stay longer than four days having undergone surgery or transplantation and mechanically ventilated for more than 48 hours were included in the study. Ventilator-associated pneumonia diagnosis was based on a combination of radiological signs (progressive infiltrate on chest radiograph), clinical signs (fever >38.3 °C, leukocytes >12×10(9)/mL) and microbiological data (positive culture from tracheal aspiration >10(5) or bronchoalveolar lavage >104 colonies/mL). Medical records of 1037 patients were reviewed and 157 patients were found to have been mechanically ventilated for more than 48 hours: 62 transplanted and 95 non-transplanted. Only 39 (24.84%) patients matched the criteria for ventilator-associated pneumonia. There were no differences in sex, age, duration of mechanical ventilation, length of stay or outcome between the two groups. However, the main difference was the mean severity score on admission (Simplified Acute Physiology Score II) which was higher among non-transplant patients (42±16 vs. 31±9; p=0.03). Gram-negative bacteria were the leading causative agents (82.03%) and were multidrug-resistant. In the intensive care surgical population, transplantation per se does not seem to increase patient risk for either ventilator-associated pneumonia acquisition or worse outcomes.

Successful management of unsuspected retroperitoneal paraganglioma via the use of combined epidural and general anesthesia: a case report.

INTRODUCTION: Similar to pheochromocytomas, paragangliomas can secrete catecholamines, although they are usually non-functional and clinical presentation is non-specific. We present a case of accidental, intra-operatively diagnosed neuroendocrine-active sympathetic paraganglioma, which was suspected and confirmed during elective retroperitoneal tumor removal. CASE PRESENTATION: A 25-year-old Caucasian Croatian man, American Society of Anesthesiologists status 1, underwent elective surgery for retroperitoneal tumor removal. The tumor had been discovered by chance during a routine examination and was suspected to be a sarcoma. Our patient had no history of previous medical conditions nor did he have symptoms characteristic of a neuroendocrine secreting tumor. The results of ultrasound and magnetic resonance imaging studies showed a large, well demarcated retroperitoneal tumor mass in his upper abdomen localized between the aorta and vena cava, measuring approximately 9×6×4.5cm. In the operating room an epidural catheter was inserted at the T7 to T8 level prior to induction of general anesthesia. Epidural analgesia was maintained by an infusion pump with local anesthetic and opiate mixture. During the surgical excision of the tumor, hemodynamic changes occurred, with hypertension (205/110mmHg) and tachycardia (up to 120 beats/minute). In spite of the fact that the surgical field of work did not include adrenal glands whose direct manipulation could explain this occurrence, there was a high degree of suspicion for the presence of a neurosecreting tumor. His clinical symptoms were relieved after administration of urapidil, esmolol and magnesium sulfate. After tumor excision, our patient developed severe hypotension. Hemodynamic stability was reinstated with aggressive volume replacement, with crystalloids and colloids, vasopressors and hydrocortisone. His post-operative course was unremarkable and on the eighth post-operative day our patient was discharged from hospital, with no consequences or symptoms on follow-up two years after surgery. CONCLUSIONS: Our patient's case emphasizes the need to consider the presence of extra-adrenal paragangliomas in the differential diagnosis of retroperitoneal tumors, despite their rare occurrence. In our patient's case, invasive hemodynamic monitoring during combined general anesthesia and epidural analgesia and early recognition of catechol-induced symptoms raised suspicion of the existence of a paraganglioma, and this led to an adequate therapeutic approach and favorable outcome of the surgery. Pre-operative recognition of paragangliomas could lead to better pre-operative preparation, but even high clinical suspicion in undiagnosed forms during surgery and the availability of rapid and short-acting vasodilatators, α-blockers and ß-blockers might favor good outcome.