International Journal of Organ Transplantation Medicine最新文献

Pulmonary vein thrombosis (PVT) is a rare condition seen almost exclusively in the first two weeks after lung transplantation or lobectomy. Subsequent embolic phenomena are uncommon. Herein, a 47-year-old male with a history of bilateral lung transplantation presented with transient episodes of acute dysphasia and right arm weakness. Brain MRI revealed cortical infarcts in the territory of the left middle cerebral artery. Transesophageal echocardiogram demonstrated a thrombus in the left lower pulmonary vein. This represents the latest manifestation of a PVT reported in the literature-6 years after redo transplantation and 13 years after the original surgery. Investigation for PVT should be considered in any patient with previous lung transplantation that presents with systemic emboli.

Background: Despite a reduction in the incidence of cytomegalovirus (CMV) infections after kidney transplantation, less is known about late CMV infection in kidney transplant recipients.

Objective: To assess incidence of CMV infection in a cohort of patients under a high surveillance CMV prevention protocol and identify factors associated with late CMV infection.

Methods: Analysis of a consecutive cohort of 181 kidney allograft recipients between January 2012 and Aug 2015. CMV prevention-protocol consisted of 6-month universal prophylaxis and pre-emptive therapy for high-risk group (D+/R- or patients submitted to lymphocyte-depleting agent for induction or rejection treatment) and pre-emptive therapy for standard-risk group (D±/R+). Stopping valganciclovir was followed by CMV screening in the next two appointments.

Results: CMV infection was identified in 73 of 181 patients; the rate in high-risk group and standard-risk group was similar (p=0.443). However, in the latter group, the infection occurred mostly in the first 6 months. Late CMV infection occurred in 25 of 181 patients (5 of standard-risk group and 20 of high-risk group), after a median (IQR) of 253 (230.3-312.3) days after transplantation and 55 (41-89.5) days after the protocol period. Screening for CMV after valganciclovir discontinuation revealed 56% of late CMV infections. In high-risk group, D+/R- was associated with late CMV infection (HR 2.7, p=0.039) and in standard-risk group; lower age was associated with late CMV infection (HR 0.89, p=0.02).

Conclusion: The incidence of CMV infection was similar to that reported in the literature. In high-risk patients, antigenemia surveillance during prophylaxis did not appear to reduce late CMV infections. Antigenemia screening after valganciclovir had limited results in the diagnosis of late CMV infection. D+/R- was associated to late CMV infection in high-risk group. Lower age appeared to influence late CMV infection in standard-risk group.

Background: There is no consistent association between individual histological lesions and composite scores in donor kidney biopsy and transplant outcomes.

Objective: To evaluate which acute or chronic individual histological lesions and composite scores in donor kidney were associated with graft survival in the recipient.

Methods: We investigated the association of individual histological lesions and 8 composite scoring systems in implantation biopsies of cadaveric (n=101) and living (n=29) kidneys with 5-year death-censored graft survival.

Results: We found a high frequency of chronic lesions in donor kidneys, mostly associated with arteriosclerosis, and less dependent from donor age. Acute, chronic, and total Banff scores for post-transplant biopsies, chronic and total Banff scores for pre-implant biopsies, donor damage score and chronic damage score predicted death-censored graft loss. However, only chronic and total Banff-scores had significant effects in multivariate model. Chronic pre-implant and total post-transplant Banff scores demonstrated the highest area under the curve (AUC) of 0.722 and 0.717, respectively. Among individual lesions, glomerulosclerosis ≥20%, interstitial inflammation >0, arteriosclerosis =3, arteriolar hyalinosis >0, and interstitial fibrosis >0, assessed with Banff-grading criteria, were associated with lower allograft survival. We created the Donor Kidney Damage Index (DKDI), by summing regression coefficients for these lesions, which yielded the AUC of 0.747. When combined with retransplantation, cold ischemia time and acute rejection, DKDI, chronic pre-implant and total post-transplant Banff scores further improved their predictive accuracy, yielding AUCs of 0.842, 0.807, and 0.802, respectively.

Conclusion: DKDI, chronic pre-implant and total post-transplant Banff scores alone and combined with clinical variables may facilitate decision making in post-transplant period.

Background: Cytokines are important factors determining the outcome of transplantation. The host ability in cytokine production may be affected by cytokine genes polymorphisms.

Objective: To investigate the effect of IL-12 and TNF-α gene polymorphisms on outcome of hematopoietic stem cell transplantation.

Methods: 90 bone marrow transplant recipients were included in this study. 30 (33%) of 90 recipients experienced graft-versus-host disease (GVHD). IL-12 and TNF-α gene polymorphisms were evaluated by PCR-RFLP and ARMS-PCR method, respectively.

Results: No significant difference in the distribution of IL-12 (rs3212227 +1188 A/C) and TNF-α (rs 1800629 -308 G/A) genotypes and alleles was observed between those with and without GVHD. There was no significant association between the distribution of genotypes and the recipient sex.

Conclusion: IL-12 (rs3212227 +1188 A/C) and TNF-α (rs 1800629-308 G/A) genotypes and alleles were not risk factors for development of GVHD.

Background: The loss or dysfunction of bone tissue that observed after bone tumor resections and severe nonunion fractures afflicts 200 million people worldwide. Bone tissue engineering is a promising approach to repair osteoporotic fractures.

Objective: In this paper, polycaprolactone (PCL)/magnesium oxide (MgO)/graphene oxide (GO) nanofibrous scaffold was fabricated by electrospining method, and its biocompatibility and osteogenic differentiation of adipose-derived mesenchymal stem cells (MSCs) on this scaffold were evaluated and compared with pure PCL nanofibrous scaffold.

Methods: SEM analysis, DAPI staining and MTT assay were used to evaluation biocompatibility of PCL/MgO/GO composite scaffold. In addition by ALP assay and proteomic approach, osteostimulatory effect of electrospun composite scaffold was investigated and the expression level of osteogenic markers including Runt-related transcription factor cbfa1/runx2 (runx2), collagen type I (Col1a1) and osteopontin (OPN) in MSCs seeded on PCL/MgO/GO composite scaffold was determined and compared with pure PCL scaffold. Then, RT-PCR technique was used to validate the level expression of these genes.

Results: The obtained results showed that adhesion, viability and ALP activity of MSCs on PCL/MgO/GO scaffold considerably enhanced compared with pure PCL. As well as proteomic and real-time analysis illustrated the expression of osteogenic markers including runx2, Col1a1 and OPN increased (>2-fold) in cells seeded on PCL/MgO/GO composite scaffold.

Conclusion: It was concluded that MgO and GO nanoparticles could improve the biocompatibility of PCL scaffold and enhance the osteogenic differentiation of MSCs.

Background: Dysregulated expression of co-stimulatory molecules is one of the immune escape mechanisms employed in hematologic malignancies like acute myeloid leukemia (AML).

Objectives: To evaluate the expression of the CD28 and CTLA-4 molecules in 62 adults with de novo AML and its correlation with the development of acute graft vs host disease (GVHD) after hematopoietic stem-cell transplantation.

Methods: The relative expression of CD28 and CTLA-4 was measured by quantitative SYBR Green real-time PCR method in a group of patients and controls as well as different risk groups (high, intermediate and favorite risk), M3 vs non-M3 and GVHD vs non-GVHD patients.

Results: The mRNA expression of CD28 (7.9-fold) and CTLA-4 (5.7-fold) was significantly increased in AML patients compared with healthy controls (p=0.006 and 0.02, respectively). Although the mean expression of both CD28 and CTLA-4 was increased in high-risk group compared with low-risk and intermediate-risk groups, the difference was not statistically significant. Also, the mean expression of the CTLA-4, but not CD28, was significantly higher in M3 patients compared with non-M3 ones (p<0.001). The expression of CD28 was upregulated in GVHD patients, while the expression of CTLA-4 was slightly lower in GVHD patients compared with non-GVHD patients, though the difference was not statistically significant. There was no significant correlation between the expression of CD28 and CTLA-4 and laboratory parameters like white blood cells and platelets counts, and hemoglobin and lactate dehydrogenase level in AML patients.

Conclusions: CD28 and CTLA-4 molecules are aberrantly expressed in peripheral blood leukocytes of AML patients and might contribute to the development of aGVHD after hematopoietic stem cell transplantation.

Background: Monitoring of chemokines, CXCL9 and CXCL10, in serum may present a non-invasive detection method for rejection.

Objective: To investigate the relationship between urinary levels of CXCL9 and CXCL10 and graft function following renal transplantation.

Methods: 75 living-related donor renal transplant recipients were studied. Urinary levels of chemokines were collected pre-operatively, on post-operative 1^st day, 7^th day, 1^st month, 3^rd month, and at the time of rejection. Chemokines levels were assayed using and enzyme-linked immunosorbent assay.

Results: Clinical variables were monitored. 10 (15%) patients had biopsy-proven rejection during the follow-up period. The urinary CXCL9 level in those with rejection was significantly higher than that in those with non-rejection group at the 1^st day (p<0.001), 7^th day (p<0.001), and at the time of rejection (p=0.002). The urinary CXCL10 level was also significantly higher in those with rejection compared with non-rejection group at 1^st day (p<0.001), 7^th day (p<0.001), and at the time of rejection (p=0.001). Serum creatinine level was strongly correlated with the urinary CXCL9 and CXCL10 levels at the time of rejection (r=0.615, p=0.002; and r=0.519, p=0.022, respectively). Among those with T cell-mediated rejections the mean urinary CXCL10 level increased to as high as 258.12 ng/mL.

Conclusion: Urinary CXCL9 and CXCL10 levels might have a predictive value for T cell-mediated rejection in early post-transplantation period. Measurement of urinary CXCL9 and CXCL10 levels could provide an additional tool for the diagnosis of rejection.

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 3^rd-5^th 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.

Background: Kidney transplantation is the most effective and optimal treatment for end-stage renal disease.

Objective: To investigate the association between serially measured ultrasound indices during the early post-operative period to determine severe acute tubular necrosis (ATN) in kidney allografts.

Methods: In a prospective study, we assessed sonographic renal indices including interlobar arteries peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI), pulsatility index (PI), power doppler grading (PDG), acceleration time (AT), and renal volume on the 3^rd and 9^th days after kidney transplantation in 46 adult recipients who had no other significant complications except ATN. Biopsies were performed in patients with prolonged delayed graft function (DGF) to exclude other pathologies, especially acute rejection.

Results: 12 (20%) recipients experienced biopsy-proven severe ATN. The differences in the ultrasound indices and their measured discrepancies on the 1^st and 2^nd examinations between the groups were not statistically significant except for the 1^st examined RI (p=0.029) and PI (p=0.04). No patient had PDG of >2. The first RI, with a cut-off value of 0.66, had a sensitivity of 91.7% and a specificity of 50% for predicting severe ATN (area under the ROC curve = 0.71). To compensate for the low specificity of this index, we suggest using the first PDG scale of equal to 2 with a specificity of 85.3%. Overall sensitivity, specificity, and positive and negative predictive values in established severe ATN throughout early post-operative days for a 3^rd day RI >0.66 and PDG = 2, were 38%, 92.5%, 64.1%, and 80.9%, respectively.

Conclusions: The RI and the PDG measured on the 3^rd day after renal transplantation are useful indices for the diagnosis of established severe ATN in kidney allografts. Furthermore, donor characteristics, post-harvesting organ preservation status, main renal vascular anastomosis, and early post-operative recipient's clinical situations may also influence the incidence of severe ATN. Although the 1^st ultrasound examination on the 3^rd day in early post-transplantation provides important diagnostic and prognostic information, repeated assessment about one week later provides no more valuable information.

Candida infections are common diseases in immunocompromised patients. A 19-year-old boy with liver transplantation, necrotic skin lesion, jaundice, dyspnea, and ascites was admitted to Namazi Hospital, Shiraz, southern Iran. The mycological examination for the skin lesion was requested. The skin sample was cultured on Sabouraud dextrose agar and evaluated by direct microscopic smear. Identification of isolated yeast was performed with RFLP-PCR. In direct smear, pseudohyphae, blastopores and yeasts were observed. Candida species was isolated from the media and identified as Candida albicans by molecular method. He died before starting any treatments. A skin lesion may present as the only sign of a systemic fungal infection in immunocompromised people. Careful attention and follow up are therefore recommended.