Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19.

Neutrophilia occurs in patients infected with SARS-CoV-2 (COVID-19) and is predictive of poor outcomes. Here, we link heterogenous neutrophil populations to disease severity in COVID-19. We identified neutrophils with features of cellular aging and immunosuppressive capacity in mild COVID-19 and features of neutrophil immaturity and activation in severe disease. The low-density neutrophil (LDN) number in circulating blood correlated with COVID-19 severity. Many of the divergent neutrophil phenotypes in COVID-19 were overrepresented in the LDN fraction and were less detectable in normal-density neutrophils. Functionally, neutrophils from patients with severe COVID-19 displayed defects in neutrophil extracellular trap formation and reactive oxygen species production. Soluble factors secreted by neutrophils from these patients inhibited T cell proliferation. Neutrophils from patients with severe COVID-19 had increased expression of arginase-1 protein, a feature that was retained in convalescent patients. Despite this increase in intracellular expression, there was a reduction in arginase-1 release by neutrophils into serum and culture supernatants. Furthermore, neutrophil-mediated T cell suppression was independent of arginase-1. Our results indicate the presence of dysfunctional, activated, and immature neutrophils in severe COVID-19.

Retransplant of the Liver: 12-Year Experience of the Shiraz Organs Transplantation Center.

OBJECTIVES: Liver transplant is the most effective treatment modality for patients with end-stage liver disease, metabolic disorders, hepatic malignancy, and acute liver failure. When a graft fails after primary liver transplant, retransplant of the liver remains the only option. Here, we report the past 12-year experience of the Shiraz Transplant Center regarding liver retransplant. MATERIALS AND METHODS: This is a retrospective cohort study of a 12-year period (2004-2015) of the Shiraz Center in Iran. RESULTS: Of the 3107 patients who had a liver transplant during the study period, 58 retransplants were performed (1.86%) in 57 patients. The leading cause of retransplant was primary nonfunction in 24 patients (41.4% of retransplant cases and 0.77% of all liver transplant cases). The second leading cause of retransplant was vascular complications in 25 patients (23 with hepatic artery thrombosis and 2 with portal vein thrombosis), accounting for 43.1% of retransplant cases and 0.80% of all liver transplant cases. In addition, 5 patients (8.6%) had retransplant for rejection, which accounted for 0.16% of all liver transplant cases. Four patients with retransplant (6.9%) had recurrence of primary disease, which accounted for 0.12% of all liver transplant cases. Most liver retransplants occurred early (≤ 30 days after primary transplant) at the Shiraz Transplant Center. Five-year survival rate after retransplant was 35%, and retransplant for hepatic artery thrombosis was more common in children. CONCLUSIONS: Because most patients required retransplants in the early period after primary transplant, the decision for retransplant must be considered carefully with full multidisciplinary evaluation and only in skilled hands. Retransplant in subgroups of patients with little chance of a successful outcome should be avoided.

Single Center Long-Term Results of Pediatric Liver Transplantation.

OBJECTIVES: Liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the rare donor organs, complex surgical demands, and the necessity to prevent long-term complications. Our objectives were to analyze 16 years of experience in the Shiraz University Organ Transplant Center. MATERIALS AND METHODS: We retrospectively analyzed the records of 752 patients (< 18 years old) who underwent orthotopic liver transplant at our center over a 16-year period. Mean age was 90 months, and male-to-female ratio was 1.25. Of the 752 transplants, 354 were whole organs, 311 were from living related donors, and 87 were in situ split liver allografts. Patient and graft survival rates were determined at 1, 3, and 5 years, and results between groups were compared. RESULTS: Overall mortality was 31.8%. The 1-, 3-, and 5-year patient survival rates were 77%, 69%, and 66%, respectively, whereas the respective graft survival rates were 75%, 68%, and 65%. We observed significant differences in survival according to graft type (log-rank test, P < .001). We also observed significant differences in survival probabilities according to age (log-rank test, P < .001). Cox regression was used to simultaneously analyze effects of age and graft type on survival. Both graft type and age significantly affected survival (P < .001). The 1-, 3, and 5-year survival rates for patients having whole organ transplants were 88%, 81%, and 78%. Patients who received living donor grafts had respective survival rates of 66%, 60%, and 58%, with rates of 65%, 47%, and 47% for patients who received split grafts. CONCLUSIONS: Our results were similar to those observed in the literature in terms of indication for transplant and posttransplant survival.

A New Consideration in Hepatic Artery Reconstruction in Adult Liver Transplant: Arterial Transposition Versus Extra-Anatomic Jump Grafts.

OBJECTIVES: In some cases of liver transplant, standard hepatic artery reconstruction may be difficult or impossible due to inadequate flow of the recipient's hepatic artery, as a result of stenosis, intimal dissection, or anomalies of the hepatic artery. We compared splenic artery transposition with extra-anatomic jump graft as 2 alternative methods for hepatic artery reconstruction in these situations. MATERIALS AND METHODS: We reviewed the files of 2135 liver transplant recipients from March 2011 to February 2016 at the Shiraz Transplant Center. Data of 93 patients with unusual hepatic artery reconstruction were analyzed to assess outcomes, morbidity, mortality, and pre- and posttransplant parameters (both clinical and paraclinical). Patients were divided into 2 groups: 17 with splenic artery transposition (splenic artery group) and 76 with extra-anatomic jump grafts (control group). RESULTS: There was only 1 occurrence (5.8%) of hepatic artery thrombosis in the splenic artery group causing extra-anatomic jump graft. However, in the control group, there were 4 occurrences (5.2%) of hepatic artery thrombosis, causing 1 revision of anastomosis and 3 retransplant procedures. No deaths due to hepatic artery complications were reported in the 2 groups. Three-year survival rate was 87.5% in the splenic artery group and 68.9% in the control group. CONCLUSIONS: Splenic artery transposition is an acceptable method for hepatic artery reconstruction in deceased-donor liver transplant procedures with no greater rates of complication or morbidity than extra-anatomic jump grafts. Less operation time and better exposure during surgery are advantages of this method.

Five Years Survival of Patients After Liver Transplantation and Its Effective Factors by Neural Network and Cox Poroportional Hazard Regression Models.

BACKGROUND: Transplantation is the only treatment for patients with liver failure. Since the therapy imposes high expenses to the patients and community, identification of effective factors on survival of such patients after transplantation is valuable. OBJECTIVES: The current study attempted to model the survival of patients (two years old and above) after liver transplantation using neural network and Cox Proportional Hazards (Cox PH) regression models. The event is defined as death due to complications of liver transplantation. PATIENTS AND METHODS: In a historical cohort study, the clinical findings of 1168 patients who underwent liver transplant surgery (from March 2008 to march 2013) at Shiraz Namazee Hospital Organ Transplantation Center, Shiraz, Southern Iran, were used. To model the one to five years survival of such patients, Cox PH regression model accompanied by three layers feed forward artificial neural network (ANN) method were applied on data separately and their prediction accuracy was compared using the area under the receiver operating characteristic curve (ROC). Furthermore, Kaplan-Meier method was used to estimate the survival probabilities in different years. RESULTS: The estimated survival probability of one to five years for the patients were 91%, 89%, 85%, 84%, and 83%, respectively. The areas under the ROC were 86.4% and 80.7% for ANN and Cox PH models, respectively. In addition, the accuracy of prediction rate for ANN and Cox PH methods was equally 92.73%. CONCLUSIONS: The present study detected more accurate results for ANN method compared to those of Cox PH model to analyze the survival of patients with liver transplantation. Furthermore, the order of effective factors in patients' survival after transplantation was clinically more acceptable. The large dataset with a few missing data was the advantage of this study, the fact which makes the results more reliable.