Successful Transplantation of Kidneys From Elderly Circulatory Death Donors by Using Microscopic and Macroscopic Characteristics to Guide Single or Dual Implantation

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual‐implanted kidney; its pair continued to function satisfactorily. Death‐censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual‐implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased‐donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.     

The discard of deceased donor kidneys in the UK

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002‐3 to 12% in 2011‐12. A national offering system for hard‐to‐place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31–80) yr. Kidneys had been offered to a median of 3 (1–12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard‐to‐place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.     

Hepatoprotective Effect of Cymbopogon Citratus Aqueous Extract Against Hydrogen Peroxide-Induced Liver Injury in Male Rats

Background

Cymbopogon citratus (Poaceae) a tropical perennial herb plant that is widely cultivated to be eaten either fresh with food or dried in tea or soft drink has been reported to possess a number of medicinal and aromatic properties. This study aimed at evaluating the protective effects of C. citratus aqueous extract against liver injury induced by hydrogen peroxide (H₂O₂), in male rats.

Materials and Methods

Twenty-five rats were randomly divided into five different groups of five animals in each group; (1) Control. (2) Received H₂O₂ (0.5%) with drinking water. (3), and (4) received H₂O₂ and C. citratus (100 mg·kg⁻¹ b wt), vitamin C (250 mg·kg⁻¹ b wt) respectively. (5), was given C. citratus alone. The treatments were administered for 30 days. Blood samples were collected and serum was used for biochemical assay including liver enzymes activities, total protein, total bilirubin and malonaldehyde, glutathione in serum and liver homogenates. Liver was excised and routinely processed for histological examinations.

Results

C. citratus attenuated liver damage due to H₂O₂ administration as indicated by the significant reduction (p<0.05), in the elevated levels of ALT, AST, ALP, LDH, TB, and MDA in serum and liver homogenates; increase in TP and GSH levels in serum and liver homogenates; and improvement of liver histo-pathological changes. These effects of the extract were similar to that of vitamin C which used as antioxidant reference.

Conclusion

C. citratus could effectively ameliorate H₂O₂-induced oxidative stress and prevent liver injury in male rats.     

Ureteric complications in recipients of kidneys from donation after circulatory death donors

A large increase in the use of kidneys from donation after circulatory death (DCD) donors prompted us to examine the impact of donor type on the incidence of ureteric complications (UCs; ureteric stenosis, urinary leak) after kidney transplantation. We studied 1072 consecutive kidney transplants (DCD n=494, live donor [LD] n=273, donation after brain death [DBD] n=305) performed during 2008‐2014. Overall, there was a low incidence of UCs after kidney transplantation (3.5%). Despite a trend toward higher incidence of UCs in DCD (n=22, 4.5%) compared to LD (n=10, 3.7%) and DBD (n=5, 1.6%) kidney transplants, donor type was not a significant risk factor for UCs in multivariate analysis (DCD vs DBD HR: 2.33, 95% CI: 0.77‐7.03, P=.13). There was no association between the incidence of UCs and donor, recipient, or transplant‐related characteristics. Management involved surgical reconstruction in the majority of cases, with restenosis in 2.7% requiring re‐operation. No grafts were lost secondary to UCs. Despite a significant increase in the number of kidney transplants from DCD donors, the incidence of UCs remains low. When ureteric complications do occur, they can be treated successfully with surgical reconstruction with no adverse effect on graft or patient survival.     

Longitudinal studies on Listeria monocytogenes and other Listeria species in two salmon processing plants

Two plants processing salmon fillets and cold smoked salmon were investigated for occurrence of Listeria in products and the environment. Analyses were conducted for a period of 31 weeks. At plant A, 252 samples were examined of which 97 were from unprocessed fish and 155 from cold-smoked fish. At plant B, 189 samples of unprocessed fish were investigated. The first examination of unprocessed fish at plant A showed a presence of L. monocytogenes and L. spp. in 81% and 19% of the samples respectively. For cold-smoked fish the figures were 43% and 23%. At plant B, L. monocytogenes was isolated in 63% of the samples. During the test period, management at the processing plant initiated various hygiene precautions to improve the sanitary situation. The last batch of analyses of unprocessed fish at plant A showed a presence of L. monocytogenes and L. spp. in 42% and. 33% of the samples respectively. For cold-smoked fish, the figures were 6% and 11%. The isolation figures at plant B for L. monocytogenes and L. spp. were 50% and 17% respectively. The hygienic precautions did not have a significant effect on the presence of L. monocytogenes and L. spp. We suggest that Listeria bacteria are a part of the resident flora and are not eliminated by current cleaning and sanitation programmes. Cold-smoking, however, gave a significant reduction in the isolation of L. monocytogenes (P = 0.0082), while the isolation of L. spp. did not decrease after this process.     

One hundred eighteen Bristow-Latarjet repairs for recurrent anterior dislocation of the shoulder prospectively followed for fifteen years: study I--clinical results

In this prospective study on the Bristow-Latarjet repair, which started in 1980 and ended in 2001, we report the outcome in 118 shoulders where the patients have been followed up for 15 years (mean, 15.2 years; range, 14.3-20.8 years). The study was based on a physical examination, scoring with the system of Rowe et al, and the patients' subjective assessment of the operative result. After 2 years, 1 of 118 shoulders had redislocated and 98% of patients were satisfied with the operative repair. At 15 years' follow-up, 1 patient had undergone revision surgery as a result of recurrence of instability. One patient had had one redislocation during the follow-up period, and one patient reported three recurrences 3 years postoperatively. This patient has had no redislocations during the last 12 years. Furthermore, one more patient had had two recurrences 9 and 12 years after surgery but was very satisfied at follow-up. Subluxations occurred once in 4 patients and several times in 7 patients. These patients were, however, satisfied with the procedures at follow-up. One patient reported posterior subluxations at follow-up. Apprehension was significantly more common in patients with bilateral instability (P =.04) and was found in 19 of 109 shoulders. Of the patients, 90 (76%) were very satisfied with the operative result, 26 were satisfied (22%), and 1 did not know. The patient with revision surgery was considered to be dissatisfied. The incidence of bilateral shoulder instability increased from 22 of 118 (19%) at the time of surgery to 41 of 117 (35%) at 15 years after surgery. We conclude that the overall clinical results, with a satisfaction rate of 98% 15 years after the Bristow-Latarjet repair, were as good as the results reported after any operative method for recurrent anterior shoulder dislocation. However, until the radiologic part of this study is completed, we recommend the procedure only for shoulders with revision because of failed previous surgery and to surgeons familiar with the method.     

Nonviral and viral gene transfer into different subsets of human dendritic cells yield comparable efficiency of transfection

Among the many promising cancer immunotherapeutic strategies, dendritic cells (DC) have become of particular interest. This study aims to optimize a clinical grade protocol for culture and transfection of human DC. Monocytes and CD34(+) hematopoietic stem cells (HSC) from same donor were differentiated under serum-free conditions and analyzed for their susceptibility to several recently described nonviral transfection methods as compared with established virally mediated gene transfer. Nonviral gene transfer methods studied were square-wave electroporation, lipofection, and particle-mediated transfer of plasmid DNA or in vitro transcribed mRNA. We conclude that DNA is not suitable for transduction of DC using nonviral methods. In contrast, mRNA and square-wave electroporation reproducibly yields 60% and 50% transfected monocyte- and CD34(+)-derived DC, respectively, measured at protein level, without affecting the cell viability. Thus, the transfection efficiency of this method is comparable with the 40-90% transgene expression obtained using retroviral (RV) or adenoviral (AdV) vectors in CD34(+)- and monocyte-derived DC, respectively. In monocyte-derived DC, however, the amount of protein expressed per-cell basis was higher after AdV (MOI = 1000) compared with mRNA electroporation-mediated transfer. This is the first study directly demonstrating side-by-side that mRNA electroporation into DC of different origin indeed results in a comparable number of transduced cells as when using virus-mediated gene transfer.     

Therapeutic effect of cimetidine on acetaminophen-induced hepatotoxicity in rabbits

Acetaminophen is an analgesic and antipyretic drug that may cause hepatic toxicity in humans and experimental animals. Cimetidine is an H₂ blocker used for suppression of gastric acid secretion. One of the side effects of cimetidine is blockade of the cytochrome P-450 enzyme system which results in increased half-life of some drug. In this study, 120 female rabbits, randomized into 12 groups (three control and nine test groups), were used. Acetaminophen, 3.24 g/kg, in suspension form as the LD₅₀, was administered orally to induce liver necrosis. Cimetidine (40 mg/kg) was administered intravenously at 0, 2, and 4 h after administration of acetaminophen. Some treatment groups received cimetidine in two equal divided doses—20 mg/kg cimetidine was administered at 2 and 12 h, 2 and 24 h, 4 and 12 h, and 4 and 24 h after administration of acetaminophen. Blood samples were collected at 0, 12, 24, and 36 h after induction of acetaminophen toxicity. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and arginase were measured in all groups and were found to be increased in acetaminophen control group and some treatment groups (p < 0.05). Results showed that the best treatment effect of cimetidine could be obtained with whole dose of cimetidine administration and 2 h after acetaminophen intake.     

Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula

Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.