فهرست مطالب

Organ Transplantation Medicine - Volume:9 Issue: 4, 2018
  • Volume:9 Issue: 4, 2018
  • تاریخ انتشار: 1397/09/14
  • تعداد عناوین: 6
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  • S P Khazraee, S M Marashi, M Kaviani *, N Azarpira Pages 145-154
    Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these approaches to overcome the complications related to such diseases. Patients exposed to mustard gas suffer from massive damage to the respiratory system. Current treatment plans are only palliative and include anti-inflammatory drugs, broncholytics, long-acting β2-agonists, and inhaled corticosteroids. As mustard gas exposure leads to chronic airway inflammation, it seems that tracheobronchomalacia, because of chronic inflammation and weakness of the supporting cartilage, is an important factor in the development of chronic and refractory respiratory symptoms. The previous studies show that regenerative medicine approaches have promising potential to improve the life quality of patients suffering from tracheal defects. It seems that the engineered tracheal graft may improve the respiratory function and decrease symptoms in patients who suffer from asthma-like attacks due to mustard gas exposure. There are several successful case reports on the transplantation of stem cell-based bioartificial grafts in structural airway diseases. Therefore, we hope that the reconstruction of tracheobronchial structure can lead to a decrease in respiratory difficulties in mustard gas-exposed patients who suffer from tracheomalacia. In the present review, we summarize the main aspects of tracheal tissue engineering and cell-based therapies and the possibilities of the application of these approaches in mustard gas-exposed patients.
    Keywords: Stem cell, Cell-based therapies, Tissue engineering, Trachea, Mustard gas
  • M Zakerinia *, A Kamgarpour, H Nemati, H R Zare, M Ghasemfar, A R Rezvani, M Karimi, H Nourani Khojasteh, M Dehghani, R Vojdani, S Haghighat, N Namdari, J Rekabpoor, M Tavazo, S Amirghofran, Z Amirghofran, G A Yosefipour, M Ramzi Pages 157-167
    Background
    Cellular transplantation is a promising treatment strategy for neurological diseases.
    Objective
    To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center.
    Methods
    From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015—10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson’s disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50–200 (median 100) mL bone marrow was aspirated from the patients’ posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3–4 hours after bone marrow collection. 5–10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4–5 hours. The median number of MNCs was 4×107 (range 1–450×107). The median viability of the cells was 90% (range 60%–98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy.
    Results
    We noted clinical improvements in 9 of 12 patients with Parkinson’s disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2–4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated.
    Conclusion
    Most patients with advanced Parkinson’s disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life.
    Keywords: Neurological diseases, Bone marrow stem cells, Intrathecal
  • B Geramizadeh *, M Hassani, K Kazemi, A R Shamsaifar, S A Malek, Hosseini Pages 168-172
    Background
    Histopathologic changes of post-reperfusion liver needle biopsies in patients with liver transplantation have rarely been reported and most of the previous reports have been in less than 200 cases.
    Objective
    In this study, we evaluated 408 post-perfusion liver needle biopsies for the histopathologic changes attributable to reperfusion injury and compared them with early post-liver transplantation outcome, to find out the value of these findings.
    Methods
    In 408 patients who underwent liver transplantation, post-perfusion liver needle biopsy was taken within one hour of vascular anastomosis. The specimens were fixed in formalin and evaluated by a hepatopathologist blinded to the outcome of transplantation for hepatocellular necrosis, apoptosis, ballooning degeneration, cholestasis, neutrophilic infiltration, and steatosis. These were compared with cold and warm ischemic time, levels of AST, ALT, alkaline phosphatase, bilirubin, presence or absence of rejection, and duration of hospital stay.
    Results
    Hepatocellular ballooning degeneration, apoptosis, and necrosis did not show any significant correlations with early post-transplantation outcome and reperfusion injury. However, presence of neutrophilic infiltration in the post-reperfusion liver biopsy was well correlated with liver function tests and other clinical and paraclinical findings. Presence of steatosis in post-reperfusion liver needle biopsy was also associated with high liver function tests and long hospital stay.
    Conclusion
    Presence of PMN leukocytes in the post-perfusion liver needle biopsy of transplanted liver is associated with poor early outcome and reperfusion injury, so it should be recorded in the pathology report and should be considered a high-risk sign for the clinicians.
    Keywords: Reperfusion, Biopsy, needle, Liver transplantation, Apoptosis, Necrosis, Histopathologic changes
  • A R Soleimani, M Jafari, A Piroozmand, H Nikoueinejad *, H Akbari, B Einollahi Pages 173-177
    Background
    Cytomegalovirus (CMV) is the most common opportunistic viral infection in kidney transplant recipients. CMV classification is usually based on its glycoprotein B (gB) genotypes, which divides the virus into 4 strains (gB1–4).
    Objective
    To determine the incidence of CMV genotypes in Iran and their relation to various clinical factors.
    Methods
    We studied 80 renal transplant recipients admitted to our transplant referral center between 2014 and 2015. All of the studied patients were monitored every 1–2 weeks for CMV infection by immunofluorescence method. There were 34 CMV-infected patients whose sera were studied with sequencing technique to identify the 4 CMV genotypes. All patients were followed up to 6 months after transplantation.
    Results
    gB1 was the most common genotype (35.3%); it was followed by gB3 and gB4 (each with 17.6 %), gB2, and mixed gB1,3 and gB1,2 (each with 14.7%). Age (p=0.037), time of infection after transplantation (p=0.011), and biopsy-proven rejection (p=0.012) were associated with CMV genotype. After adjusting for covariates, significant associations were found between genotype gB1 and family relationship (p=0.047) as well as HLA mismatch (p=0.014); genotype gB3 and family relationship (p=0.011); and genotype gB4 and age (p=0.019).
    Conclusion
    The most common CMV gB genotype in CMV-infected kidney transplant recipients in Iran was gB1. We recommend considering related therapeutic applications in the management of such patients.
    Keywords: CMV infection, Glycoprotein B, Genotype, Renal transplantation
  • M Launay *, V Baudouin, R Guillemain, A Maisin, H Flodrops, E Douez, S Mavoungou, V Jullien, E Billaud Pages 178-183
    Background
    Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce.
    Objective
    To assess the effect of leflunomide on BKvirus in kidney-transplanted children.
    Methods
    Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded.
    Results
    A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis.
    Conclusion
    This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30–40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.
    Keywords: Leflunomide, Kidney transplantation, Pediatrics, BK virus, Cystic fibrosis, Mycophenolate
  • M A Shafiee *, G Parastandechehr, S Tabatabavakili, M Shahroukh, A Haghighi, B Broumand Pages 184-191
    Granulomatosis with polyangitis (GPA) is characterized by necrotizing granulomatosis of the upper and lower respiratory tract and glomerulonephritis. If GPA does not respond to appropriate management, it might result in end-stage renal disease, which may remit the disease severity. The overall impression is that immunosuppression following renal transplantation would further subside the vasculitis. However, several studies have shown that systemic vasculitis recur in 25% of patients following renal transplantation. This may indicate the perplexing nature of the immune system. One of the key factors in prevention of relapse of GPA is following up of patients by careful immunosuppressive dose adjustment and regular measurement of biomarkers for vasculitis. Herein, we describe an interesting case of biopsy-proven GPA who had a complex long history of several post-transplantation relapses in different organs with anti-neutrophil cytoplasmic antibodies seroconversion. This case emphasizes that vasculitis in particular GPA can mimic various diseases depending on which vessels and organs are affected by the inflammation and is one of the reversible causes of failure of transplanted kidney. Bearing the diagnosis in mind as one of the potential differential diagnoses of failure of renal transplantation will lead to early diagnosis and treatment of recurrent GPA.
    Keywords: Granulomatosis with polyangitis, ANCA, Kidney transplant