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Mojtaba Shafiekhani,1,2 Iman Karimzadeh,1 Saman Nikeghbalian,2 Mohammad Firoozifar,2 Gholamreza Pouladfar,3 Afsaneh Vazin1 1Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2Shiraz Organ Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran; 3Professor Alborzi Clinical Microbiology Research Center, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, IranCorrespondence: Afsaneh VazinSchool of Pharmacy, Shiraz - Marvdasht Hwy, Rokn Abad Town, Shiraz, Fars Province 71468 64685, IranTel +98 71 32 42 41 27Fax +98 71 32 42 41 26Email vazeena@sums.ac.ir Gholamreza PouladfarNemazee Hospital, Karimkhan Zand St, Shiraz, Fars Province 7193711351, IranTel +98 71 36474296Fax +98 71 36474303Email pooladfar@sums.ac.irPurpose: In this study, we aimed to compare the efficacy of combined ceftizoxime with ampicillin-sulbactam versus combined gentamicin with ampicillin-sulbactam as prophylactic antibiotic regimen in preventing early bacterial PTIs in liver TX recipients at a referral center.Patients and methods: All patients older than 18 years who had undergone liver TX at Abu-Ali Sina transplantation center in Shiraz, Iran from July 2018 to April 2019 were included in this study. In a single-blinded manner, the participants randomly received either combined intravenous ceftizoxime plus ampicillin-sulbactam (ceftizoxime group) or gentamicin plus ampicillin-sulbactam (gentamicin group) as prophylactic antibiotic regimen before the incision of the surgery, which was continued for 48 hrs after liver Tx. The rate and type of bacterial infections, length of hospital and intensive care unit (ICU) stay, mortality rate, and kidney function were assessed during 1 month following liver TX in the two groups.Results: Two hundred and thirty patients were divided into two groups. One patient in the gentamicin group and five in the ceftizoxime group were excluded due to emergency exploratory laparotomy within the first 3 days after transplantation. The rate of bacterial infections during the first month after transplantation was 25.4%. This rate was significantly lower in the gentamicin group (13.16%) in comparison to the ceftizoxime group (38.18%) (P value

Background: Liver transplantation is the main treatment for tyrosinemia. The pre-operative conditions such as presence of failure to thrive (FTT) would affect the prognosis of transplant recipients. Objective: To test whether the survival rate of liver transplant recipients with tyrosinemia was associated with pre-operative presence or absence of FTT. Methods: In a historical cohort study, the survival rate of 42 liver transplant recipients with FTT was compared with that of 68 patients without FTT during 6 months of the transplantation. Kaplan-Meier survival analysis and Cox regression were used for data analysis. Results: The recipients with and without FTT were matched for age, sex, baseline laboratory test results, and the frequency distribution of the underlying diseases. 35 (83%) of 42 recipients with FTT and 29 (43%) of 68 without FTT had rickets (p<0.001). Histopathological study of the resected livers revealed that 50% of those with FTT and 77% of recipients without FTT had hepatocellular carcinoma or hepatoblastoma (p=0.015). Recipients with FTT were followed for a median (IQR) of 62 (23-99) days; those without FTT, 31 (6-85) days. During the follow-up period, 9 (21%) of 42 recipients with FTT and 32 (47%) of 68 without FTT died. Recipients with FTT had a significantly (p=0.013) better survival. Presence of FTT in recipients was associated with a 65% reduction (HR 0.35, 95% CI 0.158-0.776) in the risk of death within 6 months of the transplantation. Conclusion: Presence of FTT in patients with tyrosinemia undergoing liver transplantation, would significantly decrease the short-term mortality rate in transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation can increase survival and quality of life in patients with end-stage renal disease. In any allocation system, the crossmatch test plays an essential role in donor-recipient compatibility. Objective: In this study, we aim to test the benefits of a web-based program that captures HLA antibody analyses and provides a report to allow fast and accurate virtual crossmatches. Methods: One hundred potential recipients in the waiting list of renal transplants were selected. The included patients all had a complete HLA antibody profile. Also, 10 potential donors from previous kidney transplants (2020), with available HLA typing results for A, B, and DR locus, were also selected. A comparison was made between 100 recipients against ten potential donors, and virtual crossmatching (VXM) was performed by the web-based program and manually by an experienced immunologist. Results: The average time for a manual VXM was 30 minutes per patient, while the virtual cross webbased program took 5 minutes per patient. In 12% of the manual VXM cases, a secondary review of data improved final results. In two manual virtual crossmatches, the VXM results had errors in matching recipient antibodies with the donor HLA typing that could affect the final decision for transplantation.. Conclusion: In conclusion, a web-based VXM program that assesses HLA data can accurately perform a VXM with fewer human errors. It is especially true for highly sensitized candidates. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating liver transplantation (LT) in hepatocellular carcinoma (HCC) in the Middle East have been scarce, mainly due to intricacy of this type of surgery. Objective: In here we report our experiences with LT among patients with HCC cirrhosis. Methods: All patients who underwent LT with primary diagnosis of HCC older than 18 years old, during 2004 to 2019, were initially included in our study. Results: Overall, 124 patients entered our study, among which majority were males (86.3%). Mean (SD) age of patients was 53.1±10.6 years old. Most common underlying liver diseases were HBV (55.6%) and HCV infections (12.1%). Mean MELD score of patients was 18±5.5. Child-puge score of most patients was class B (50%). Mean (SD) duration of hospitalization was 12.1±3.5 days. Patients were followed for a median of 32 (9, 62) months. The most common causes of death were recurrence of HCC (47.7%) and sepsis (34.1%). Median (IQR) duration to recurrence and death were 18 (4, 34) months and 17.5 (5.7, 44.5) months, respectively. One-year survival (89%, 86.4%, and 63.2%, respectively) (p=0.011) and one year DFS (89%, 86.4%, and 57.9%, respectively) (p=0.001) was significant different between those who were selected based on the Milan, UCSF and extended criteria. Conclusion: Our study provides valuable experiences on LT and HCC from one of the largest LT center in the world. Accordingly, we found that the Milan criterion provides the best survival compared to the UCSF and our extended criteria for patient selection. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion injury during transplantation can cause post-operative graft dysfunction. Objective: To assess the efficacy of N-acetylcysteine in preventing hepatic ischemia-reperfusion injury and post-transplant outcomes. Methods: In this retrospective study on pediatrics undergoing living-donor (from one of their parents) liver transplantation, N-acetylcysteine was administered to one group (n=20) after induction in the donors until graft harvest, and in the recipients during implantation, which was maintained for 19 hours. The second group (n=20) did not receive NAC. Early allograft dysfunction was determined in the presence of alanine aminotransferase or aspartate aminotransferase =2000 IU/L and bilirubin =10 mg/dL within the first 7 days, and an international normalized ratio =1.6 on day 7. Data were collected from a retrospectively maintained database. Results: The incidence of post-reperfusion syndrome was lower in N-acetylcysteine group compared with the other group (5% vs. 30%, p=0.037). Serum creatinine level was significantly (p=0.04) different in the N-acetylcysteine group during the second post-operative week (0.14 vs. 0.15 mg/dL). There was no significant difference in the incidence of early allograft dysfunction (21% vs. 14%, p=0.327), and the survival rate (p=0.409). Conclusion: Peri-operative infusion of N-acetylcysteine in both donor and recipient would effectively prevent post-reperfusion syndrome and renal insufficiency. However, it might not affect the early allograft dysfunction, ICU stay, and mortality. NAC increases the chance of re-operation due to non-surgical bleeding in the first post-operative day. [ABSTRACT FROM AUTHOR]

Background: Probable effects of living donor liver transplantation on the wellbeing of the donor and psychological difficulties are necessary to be understood. Objective: To assess the quality of life of living donors after liver donation. Methods: 140 living donors who underwent hepatectomy between 2012 and July 2015 were enrolled in this study. Donors were asked to complete the Short Form 36-question Health Survey (SF-36) through face to face or by telephone interview. Results: The mean±SD age of donors at transplantation was 32.1±7.3 years; 83 (59.3%) of donors were female. 134 (95.7%) were married. The mean±SD BMI was 23.8±3.5 (kg/m2). "Mother-to-child" was the most frequent relationship (n=79, 56.4%). 22 (15.7%) complications were reported by participants. The mean±SD score of Physical Component Summary and Mental Component Summary were 48.8±14.6 and 50.1±6.9, respectively. Conclusion: Most living donors sustain a near average quality of life post-donation. It seems that living donation does not negatively affect the quality of life. [ABSTRACT FROM AUTHOR]

Background: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and in vitro study of drug toxicity. Objective: To determine which cold preservation solution is better maintain the liver function. Methods: We prepared 4 cold preservation solutions made of different combination of antioxidants, chelating, membrane protective, and anti-apoptotic agents as well as inhibitor of cyclophilin D. For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. After culture and cold preservation, the level of albumin, and urea production were measured as indices of liver functionality. Results: We found that albumin production significantly decreased after cold preservation in solution 1. There was no significant difference in urea production after cold preservation in solution 1 compared with control 24 h. No significant differences in albumin production were found after cold storage in solution 2 and solution 4 compared with control 24 h. Urea production significantly decreased after cold storage in solutions 2 and 4 compared with control 24 h. As a whole albumin and urea production were significantly decreased after cold preservation. Although albumin and urea production were decreased after cold preservation, but the results of albumin production of two solutions were not significantly different from that of the control group (p=0.109 and 0.951). Conclusion: Cold preservation of cultured human hepatocytes in solution 2 and solution 4 could maintain the function of albumin production better than other cold preservation solutions in our experiments; solution 1 was more effective on urea production of cultured human hepatocytes at 4 °C for 24 h. To determine if these hepatocytes are suitable candidates for transplantation, further studies should be performed. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. Objective: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. Methods: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and antioxidative solutions, i.e., a-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. Results: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. Conclusion: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells are one of the most interesting cell sources used in regenerative medicine. Objective: In the present study, we isolated and characterized the mesenchymal stem cells from various compartments of human adipose tissue and tunica adventitia layer of the arteries. Methods: Tissue explant culture was done from various compartments of the human adipose tissue and tunica adventitia layer of the arteries, including adipose tissue far from the vessels, perivascular tissues that are completely attached to the vessels, and tunica adventitia layer of the arteries. After the cell culture, characterization of the cells was determined at 3rd-5th passages. Flow cytometry was performed for antigen expression analysis of CD34, CD45, CD44, CD90, CD29, CD73, and CD105. For the evaluation of cell differentiation potential, adipogenic and osteogenic differentiation was conducted under appropriate protocols. Results: The cells were positive for CD44, CD90, CD29, and CD73 and negative for CD34, CD45, and CD105. Adipogenic and osteogenic differentiation potentials were different among the cells from various compartments. The cells derived from perivascular tissue demonstrated better adipogenic and osteogenic differentiation. Conclusion: It is essential to characterize the cells from different tissues and compartments for different purposes in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Cytokines and co-stimulatory molecules are important factors determining the outcome of transplantation. Objective: To investigate the effect of IL-18 and CD40 gene polymorphisms on the outcome of liver transplantation. Methods: 150 liver transplant recipients were included in this study. Alleles and genotypes frequencies for IL-18 (rs1946519) and CD40 (rs1883832) were determined in 28 acutely rejected (AR group) and 122 non-acutely rejected (non-AR group) liver transplant recipients. IL-18 and CD40 gene polymorphisms were evaluated by PCR-RFLP methods. Results: There were no significant associations between IL-18 and CD40 polymorphism with acute rejection in liver transplant patients. IL-18TT and TG genotypes had a significant association with rejection in women compared to men. After grouping the liver recipients according to living vs cadaver donors, a significant association was found between CC genotype of CD40 and rejection in male living donor recipients. IL-18 TG genotype had a significant association with rejection in female cadaver donor recipients. Conclusion: There is no correlation between all genotype and alleles of IL-80 and CD40 polymorphism and the outcome of liver transplantation. However, gender and type of donor affect the correlation between all genotype and alleles of IL-18 and CD40, and the outcome of liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Tumors involving the root of the mesentery are generally regarded as "unresectable" with conventional surgical techniques. Resection with conventional surgery may end in life-threatening complications in these patients. Ex-vivo resection and auto-transplantation avoids excessive bleeding and prevents ischemic related damage to the small intestine and other organs. Objective: To share our experience of ex-vivo resection of the tumors with involvement of small bowel mesentery followed by small bowel auto-transplantation. Methods: In this study, medical records of all the patients who underwent ex-vivo resection and autotransplantation at our center were retrospectively analyzed. Results: The most common indication for the procedure in our series was locally advanced pancreatic carcinoma. Our survival rate was 50% with a mean±SD follow-up of 10.1±9.8 (range: 0-26) months. Causes of early in-hospital mortality were multi-organ failure, sepsis, and cerebrovascular accident. Recurrence of disease was noted in one patient while one patient developed hepatic metastasis after 20 months of surgery. Conclusion: Ex-vivo resection of the tumor and auto-transplantation is the surgical treatment of choice for the locally advanced abdominal tumors involving the root of the mesentery. [ABSTRACT FROM AUTHOR]

Background: Multivisceral transplantations were initially done in animal models to understand the immunological effects. Later on, in human beings, it has been considered a salvage procedure for unresectable complex abdominal malignancies. With advancement in surgical techniques, availability of better immunosuppressive drugs, and development of better post-operative management protocols, outcomes have been improved after these complex surgical procedures. Objective: To analyze and report results of multivisceral, modified multivisceral, and small bowel transplantations done at Shiraz Organ Transplant Center, Shiraz, southern Iran. Methods: Medical records of all patients who underwent multivisceral, modified multivisceral, and small bowel transplants were retrospectively analyzed. Results: There were 18 patients. The most common indications for the procedure in our series were unresectable carcinoma of pancreas followed by short bowel syndrome. 10 patients were alive after a median follow-up of 8.7 (range: 3-32) months. The remaining 8 patients died post-operatively, mostly from septicemia. Conclusion: Multivisceral and small bowel transplantations are promising treatments for complex abdominal pathologies. [ABSTRACT FROM AUTHOR]

The article presents a guideline on the management of brain dead patients from the Shiraz University of Medical Sciences in Iran. The said document offers information on key medical interventions in brain dead cases including respiratory aids and ventilator settings, hemodynamic interventions, and cardiovascular aids. Also provided are proposed instructions on hormonal treatments, body temperature regulation, and patient monitoring.

Background: Solid organ transplantation is the only definitive treatment available for patients with end- stage organ failure. Organs procured from brain-death donors are the main source of transplants. Following brain death, a burst of inflammatory reaction develops; it is characterized by increased plasma levels of cytokines. This inflammatory reaction has been associated with increased early allograft dysfunction. Objective: In this study, we test if the increased inflammatory response in brain-death donors is associated with more recipient complications. Methods: We prospectively recruited 38 consecutive brain-death donors admitted to the intensive care units (ICUs) of Shiraz University of Medical Sciences. Following the declaration of brain death, the demographics data on donor and recipient characteristics and cause of brain death were recorded. The post-liver transplant complications in recipients were stratified according to the Clavien classification. Plasma levels of cytokines IL-6, IL-2, and TNF-α were measured using enzyme linked immunosorbent assay (ELISA) kits, in all donors before organ procurement. Results: The mean (range) age of donors was 44 (16-74) years. Trauma due to car accident was the most common cause of brain death (79%). The post-liver transplant complications occurred in 19 (50%) recipients. The mean±SD plasma TNF-αconcentration was significantly (p<0.001) higher in recipients with grade 1-3 post-transplant complications (68.33±27.74 pg/mL) than those without complication (22.09±4.14 pg/mL). Recipients with complications had also a significantly (p=0.001) higher mean±SD donor plasma concentration of IL-6 (1009±375.5 pg/mL) compared to those without complications (779±202 pg/mL). No significant differences was observed between the two groups in respect to IL-2 concentration (0.295±0.333 vs 0.285±0.342 U/mL, p=0.207). Six recipients died of complications (grade5), in whom no correlation could be found with donor plasma cytokine concentrations. Conclusion: Higher plasma concentrations of IL-6 and TNF-α in donors before organ procurement, are associated with more post-operative complications in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is the best available treatment for patients with end-stage renal disease. Objective: To evaluate the en bloc anastomosis technique for unilateral dual kidney transplantation (DKT). Methods: From May to October 2011, 5 patients (4 women and 1 man) with mean age of 31.8 years underwent unilateral DKT with this technique in which distal end of the aorta and proximal end of inferior vena cava (IVC) were closed with running sutures. Then, proximal end of the aorta and distal end of the IVC were anastomosed to internal (or external) iliac artery and external iliac vein, respectively. Results: Post-operative course was uneventful. No vascular and urologic complications developed; all patient had acceptable serum creatinine at discharge time and up of 2-6 months of post-operation follow up. Conclusion: Unilateral DKT is a safe method for performing DKT. The proposed en bloc anastomosis can improve the outcome of the graft by reducing the cold ischemia and the operation time. [ABSTRACT FROM AUTHOR]

Background: End-stage liver diseases are common in Iran. The only therapeutic option for these patients is liver transplantation. Objective: To present our 2-year experience of liver transplantations in Afzalipoor Hospital, Kerman, southeastern Iran. Methods: From November 2009 to September 2011, 12 patients underwent orthotopic liver transplanta- tion in our center. Their data including demographics, indications for transplantation, MELD scores, post- operative complications and their management were collected. Results: Patients (7 women and 5 men) aged between 14 and 55 years. Indications for the transplanta- tion included HBV infection (n=5), cryptogenic cirrhosis (n=2), Wilson's disease, alcoholism (n=1), HCV infection (n=1), Budd-Chiari syndrome (n=1), and autoimmune hepatitis (n=1). MELD score of patients ranged from 16 to 30. All patients received tacrolimus, mycophenolate mofetile and corticosteroid, post- operatively. 2 patients died of pulmonary and intra-abdominal infections with resultant to multiple organ failure. Nonfunctioning of transplanted liver and ongoing bleeding resulted in death in another patients. 9 patients are well doing and have excellent liver functions. Conclusion: We had relatively successful results in our experience of orthotopic liver transplantation. Vicinity of our center to Shiraz Transplant Center would be an important factor in this success. [ABSTRACT FROM AUTHOR]

Background: Co-stimulatory molecules play a critical role in regulating T-cell function during CMV infection after liver transplantation. Objective: To investigate the relationship between the polymorphisms of the co-stimulatory genes and the susceptibility to CMV infection after liver transplantation. Methods: Single nucleotide polymorphisms (SNPs) in PD-1 gene (PD1.1 A/G, PD1.3 A/G, PD1.9 C/T) ICOS (-693 A/G, 1720 C/T), CTLA-4 gene (-318 C/T, 1722 T/C, 1661 A/G, 49 A/G) and CD28 (+17 C/T) were analyzed by PCR-RFLP in 70 liver transplant patients. CMV infection was determined in these patients by antigenemia test. Results: CTLA-4 49G showed significant association with CMV infection (p=0.03, OR=3.82, 95% CI: 0-3.5; p=0.01, OR=004, 95% CI: 0-1.3). G and T alleles in CTLA-4 gene (-318 C/T and 1661 A/G) (p=0.03, OR=0, 95% CI: 0-3.5; p=0.01, OR=0.04, 95% CI: 0-1.3) were significantly higher in CMV-infected rejector group. Conclusion: CTLA-4 have significant role in CMV pathogenesis and rejection among CMV-positive liver transplant patients. [ABSTRACT FROM AUTHOR]