Israel Medical Association Journal

Background: Consent rates for organ donation remain one of the most important factors determining the number of organs available for transplantation. Trauma casualties constitute a substantial part of the deceased organ donor pool and have unique characteristics that distinguish them from the general donor population. However, this group has not been extensively studied.

Objectives: To identify donor factors associated with positive familial consent for solid organ donation among trauma casualties.

Methods: This retrospective study included all trauma casualties who were admitted to the Rabin Medical Center, Beilinson hospital, during the period from January 2008 to December 2017, who were potential organ donors. Data collected included demographic features, the nature of the injury, surgical interventions, and which organs were donated. Data was collected from the Rabin Medical Center Trauma Registry.

Results: During the study period 24,504 trauma patients were admitted and 556 died over their hospital course. Of these 76 were potential donors, of whom 32 became actual donors and donated their organs. Two factors showed a statistically significant correlation to donation, namely female gender (P = 0.018) and Jewish religion of the deceased (P = 0.032).

Conclusions: Only a small group of in hospital trauma deaths were potential solid organ donors (13.7%) and less than half of these became actual donors. Consent rates were higher when the deceased was female or Jewish

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

Background: The lack of organs for liver transplantation has prompted transplant professionals to study potential solutions, such as the use of livers from donors older than 70 years. This strategy is not widely accepted because potential risks of vascular and biliary complications and recurrence of hepatitis C.

Objectives: To examine the efficacy and safety of liver grafts from older donors for transplantation.

Methods: A retrospective analysis of data on 310 adults who underwent deceased donor liver transplantation between 2005 and 2015 was conducted. We compared graft and recipient survival, as well as major complications, of transplants performed with grafts from donors younger than 70 years (n=265, control group) and those older than 70 years (n=45, older-donor group), followed by multivariate analysis, to identify risk factors.

Results: There was no significant difference between the control and older-donor group at 1, 5, and 10 years of recipient survival (79.5% vs. 73.3%, 68.3% vs. 73.3%, 59.2% vs. 66.7%, respectively) or graft survival (74.0% vs. 71.0%, 62.7% vs. 71.0%, 54.8% vs. 64.5%, respectively). The rate of biliary and vascular complications was similar in both groups. Significant risk factors for graft failure were hepatitis C (hazard ratio [HR] = 1.92, 95% confidence interval [95%CI] 1.16–2.63), older donor age (HR = 1.02, 95%CI 1.007–1.031), and male gender of the recipient (HR = 1.65, 95%CI 1.06–2.55).

Conclusion: Donor age affects liver graft survival. However, grafts from donors older than 70 years may be equally safe if cold ischemia is maintained for less than 8 hours.

Background: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs).

Objectives: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. 

Methods: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded.

Results: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6–12 months follow-up. 

Conclusions: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

 

Background: The number of patients awaiting organ transplantation continues to exceed the number of available organs. 

Objectives: To document changes in the demographic characteristics of brain-dead, heart-beating organ donors over the past 10 years which may impact on organ utilization. 

Methods: Data were extracted from the Israel Transplant Registry and the Donor Action database for the 10 year period 2004–2013, inclusive. 

Results: The median age of the donors increased from 44 (range 3–73 years) to 53.5 years (range 1–79 years) (P < 0.001). There was a significant increase in the median age of donors of kidney (33 to 51 years, P < 0.001), liver (41 to 53 years, P < 0.001) and lung (40 to 49.5 years, P < 0.001). The number of donors dying from trauma decreased (34.5% to 20%, P < 0.001), while those with anoxic brain damage increased (14.5% to 25%, P < 0.001). The percent of male donors decreased over the study period, from 63% to 53%. An increase was noted in the mean number of organs transplanted per donor, from 3.29 to 3.82 per donor, due mainly to a significant increase in the utilization of lungs (31.5% to 51.3%, P < 0.001) and livers (76.3% to 82.4%, P < 0.001) while heart utilization decreased significantly since 2006 (40.9% to 17.5%, P < 0.001). 

Conclusion: Trends in the heart-beating, brain-dead organ donor pool in Israel over the past 10 years reveal significant changes in demographic characteristics which in the future will impact on the number of organs available for transplantation. 

 

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

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[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

Background: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.

Objectives: To study the impact of combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. 

Methods: Between September 1997 and January 2000, 129 patients underwent living related (n=80) or unrelated (n=49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF[1] with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.

Results: LUD[2] recipients were older (47.8 vs. 33.6 years) with higher number of re-transplants (24.5% vs. 11.2% in LRD[3] recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 year graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.

Conclusions: Despite HLA[4] disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Background: Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepting older donors. 

Objectives: To compare the 1 year follow-up in patients after lung transplantation from older donors (>50 years old) and in patients after transplantation from younger donors (± 50 years).

Methods: The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: ≤ 50 years (n=20) and > 50 years (n=9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation.     

Results: We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation.

Conclusions: Donor age did not influence survival or important secondary end-points 1 year after lung transplantation. By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability. 

Background: Hepatitis B is a major problem worldwide. Israel has intermediate endemicity for hepatitis B virus, and an annual carrier rate of 1-3%.

Objective: To evaluate both the prevalence of HBV infection among family members of HBV carriers and the competence of family practitioners in performing a compre­hensive assessment.

Methods: A total of 152 HB surface antigen-positive blood donors were discovered in our subdistrict during the years 1993-97. Their family physicians were questioned regarding the patients' family members. Specific information on 85 spouses and 200 children was also obtained.

Results: Among the 85 married carriers, 5 of the spouses (5.9%) were found to be HBsAg positive. None of the 200 children was HB5Ag positive. We found that in a third (n=52) of the patients, the sexual partner had never been tested by a primary care physician. Patients were not routinely tested for HB e antigen or anti-HBe antibodies. Neither the parents nor the siblings had undergone any serological evaluation. How­ever, most family members of the carriers had received an HBV vaccine from their family physicians.

Conclusions: Our findings show that horizontal transmis­sion of HBV among spouses of HBV carriers still exists. We did not find any vertical transmission, probably due to male predominance and previous vaccination. Family physicians should be trained to perform an extensive serological evalua­tion of family members of patients with chronic HBV infection, including parents and siblings, and should vaccinate sero­negative family members.