Ex-Vivo Preservation of Heart Allografts-An Overview of the Current State.

As heart transplantation continues to be the gold-standard therapy for end-stage heart failure, the supply-demand imbalance of available organs worsens. Until recently, there have been no advances in increasing the donor pool, as prolonged cold ischemic time excludes the use of certain donors. The TransMedics Organ Care System (OCS) allows for ex-vivo normothermic perfusion, which allows for a reduction of cold ischemic time and allows for long-distance procurements. Furthermore, the OCS allows for real-time monitoring and assessment of allograft quality, which can be crucial for extended-criteria donors or donation after cardiac death (DCD) donors. Conversely, the XVIVO device allows for hypothermic perfusion to preserve allografts. Despite their limitations, these devices have the potential to alleviate the supply-demand imbalance in donor availability.

Donation after circulatory death heart transplantation using normothermic regional perfusion:The NYU Protocol.

Objective: This study aimed to evaluate the impact of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion on the metabolic milieu of donation after cardiac death organ donors before transplantation. Methods: Local donation after cardiac death donor offers are assessed for suitability and willingness to participate. Withdrawal of life-sustaining therapy is performed in the operating room. After declaration of circulatory death and a 5-minute observation period, the cardiac team performs a median sternotomy, ligation of the aortic arch vessels, and initiation of thoraco-abdominal normothermic regional perfusion via central cardiopulmonary bypass at 37 °C. Three sodium chloride zero balance ultrafiltration bags containing 50 mEq sodium bicarbonate and 0.5 g calcium carbonate are infused. Arterial blood gas measurements are obtained every 15 minutes after every zero balance ultrafiltration bag is infused, and blood is transfused as needed to maintain hemoglobin greater than 8 mg/dL. Cardiopulmonary bypass is weaned with concurrent hemodynamic and transesophageal echocardiogram evaluation of the donor heart. The remainder of the procurement, including the abdominal organs, proceeds in a similar controlled fashion as is performed for a standard donation after brain death donor. Results: Between January 2020 and May 2022, 18 donation after cardiac death transplants using the thoraco-abdominal normothermic regional perfusion protocol were performed at our institution. The median donor age was 42.5 years (range, 20-51 years), and 88.9% (16/18) were male. The mean total donor cardiopulmonary bypass time was 88.8 ± 51.8 minutes. At the beginning of cardiopulmonary bypass, the average donor lactate was 9.4 ± 1.5 mmol/L compared with an average final lactate of 5.3 ± 2.7 mmol/L (P<.0001). The average beginning potassium was 6.5 ± 1.8 mmol/L compared with an average end potassium of 4.2 ± 0.4 mmol/L (P<.0001) . The average beginning hemoglobin was 6.8 ± 0.7 g/dL, and the average end hemoglobin was 8.2 ± 1.3 g/dL (P<.001) . On average, donation after cardiac death donors received transfusions of 2.3 ± 1.5 units of packed red blood cells. Of the 18 donors who underwent normothermic regional perfusion, all hearts were deemed suitable for recovery and successfully transplanted, a yield of 100%. Other organs successfully recovered and transplanted include kidneys (80.6% yield), livers (66.7% yield), and bilateral lungs (27.8% yield). Conclusions: The use of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion is a burgeoning option for improving the quality of organs from donation after cardiac death donors. Meticulous intraoperative management of donation after cardiac death donors with a specific focus on improving their metabolic milieu may lead to improved graft function in transplant recipients.

Analysis of Donor to Recipient Pathogen Transmission in Relation to Cold Ischemic Time and Other Selected Aspects of Lung Transplantation-Single Center Experience.

BACKGROUND: Infections are one of the leading causes of death in the early postoperative period after lung transplantation (LuTx). METHODS: We analyzed 59 transplantations and culture results of the donor bronchial aspirates (DBA), graft endobronchial swabs (GES), and recipient cultures (RC) before and after the procedure (RBA). We correlated the results with a cold ischemic time (CIT), recipient intubation time, and length of stay in the hospital and intensive care unit (ICU), among others. RESULTS: CIT of the first and second lungs were 403 and 541 min, respectively. Forty-two and eighty-three percent of cultures were positive in DBA and GES, respectively. Furthermore, positive results were obtained in 79.7% of RC and in 33.9% of RBA. Longer donor hospitalization was correlated with Gram-negative bacteria isolation in DBA. Longer CIT was associated with Gram-positive bacteria other than Staphylococcus aureus in GES and it resulted in longer recipient stay in the ICU. Furthermore, longer CIT resulted in the development of the new pathogens in RBA. CONCLUSION: Results of GES brought more clinically relevant information than DBA. Donor hospitalization was associated with the occurrence of Gram-negative bacteria. Positive cultures of DBA, GES, and RBA were not associated with recipient death.

Impact of cold ischemia time of donor liver on early recovery after liver transplantation / 中华器官移植杂志

Objective:To explore the impact of donor cold ischemia time(CIT)on early recovery after liver transplantation(LT).Methods:From January 2016 to December 2020, the relevant clinical data were retrospectively reviewed for 456 LT recipients.According to the value of CIT of donor liver, they were assigned into two groups of CIT >5 h and CIT≤5 h. T, Mann-Whitney U or Chi square test was employed for statistical processing.Intraoperative findings and liver function(LF)parameters of two groups were compared, including operative duration, intraoperative volume of hemorrhage, erythrocyte transfusion and anhepatic phase.LF parameters included alanine aminotransferase(ALT), aspartate aminotransferase(AST)and total bilirubin(TB)within Day 1-7 post-LT.Postoperative recovery was evaluated by postoperative stay of intensive care unit(ICU), normalization time of liver function recovery, length of postoperative hospitalization and incidence of postoperative complications.Results:Among them, 407(89.3%)patients underwent classic orthotopic LT.Median CIT of donor liver was 309 min.In CIT≤5 h and CIT >5 h groups, operative duration was[(446.3+ 76.8)vs.(526.0+ 98.1)min], anhepatic phase time[(51.9+ 13.3)vs.(62.6+ 18.9)min]and intraoperative volume of erythrocyte transfusion[(7.3+ 5.8)vs.(10.0+ 6.87)U]. And the differences were statistically significant( P<0.001, 0.001 & 0.001). Postoperative hospitalization stay was longer[(29.1±15.9)vs.(27.1±13.0)]day.And the incidence of postoperative complications was higher in CIT >5 h group[22.7%(54/238)vs.12.4%(27/218)]. And the difference was statistically significant( P=0.045 & 0.004). As compared with CIT≤5 h group, ALT, AST & TB spiked in CIT >5 h group at Day 1 post-operation and the differences were statistically significant( P=0.002, P<0.001, P=0.001). In CIT >5 h group, ALT rose at Day 2/5/6/7 post-LT( P=0.026, 0.026, 0.015 & 0.011), AST jumped from Days 2-6( P=0.002, 0.004, 0.035, 0.029 and 0.019)and TB increased from Days 2-7 post-LT and the differences were statistically significant( P=0.003, 0.014, 0.030, 0.039, 0.027 & 0.009). LF recovered at CIT≤5 h and CIT>5 h group[(10.0±3.2)vs.(10.7±3.3)day]. There were significantly statistical differences( P=0.044). Conclusions:Non-conducive to patient recovery, prolonged cold ischemic time aggravates early LF injury post-LT.

Dynamic Parameters of Hypothermic Machine Perfusion-An Image of Initial Graft Function in Adult Kidney Transplantation?

Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5−28.5] vs. 11.3 [5.4−24.1], p < 0.0001). The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts (arterial flow 22.50 [18.00−48.00] vs. 51.83 [25.50−92.67] ml/min, p = 0.0256; organ resistance 123.33 [57.67−165.50] vs. 51.33 [28.17−111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08−7.64] vs. 1.67 [0.90−6.56], p < 0.0001) and at 1 year post transplant (1.80 [1.09−7.95] vs. 1.59 [0.87−7.40], p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome.

Is the Organ Care System (OCS) Still the First Choice With Emerging New Strategies for Donation After Circulatory Death (DCD) in Heart Transplant?

The scarcity of donor hearts continues to be a challenge in transplants for advanced heart failure patients. With an increasing number of patients on the waiting list for a heart transplant, the discrepancy in the number between donors and recipients is gradually increasing and poses a new challenge that plagues the healthcare systems when it comes to the heart. Several technologies have been developed to expand the donor pool in recent years. One such method is the organ care system (OCS). The standard method of organ preservation is the static cold storage (SCS) method which allows up to four hours of safe preservation of the heart. However, beyond four hours of cold ischemia, the incidence of primary graft dysfunction increases significantly. OCS keeps the heart perfused close to the physiological state beyond the four hours with superior results, which allows us to travel further and longer distances, leading to expansion in the donor pool. In this review, we discuss the OCS system, its advantages, and shortcomings.

Effect of prolonged cold ischemia time on outcomes after lung transplantation / 中华器官移植杂志

Objective:To evaluate the effect of prolonged graft cold ischemia time(CIT)on outcomes of lung transplantation(LTx).Methods:Clinical data are retrospectively reviewed for 111 patients undergoing LTx at Affiliated Shanghai Pulmonary Hospital of Tongji University between January 2019 and January 2022. They are divided into two groups of prolonged CIT(8~12 h, 41 cases)and control(<8 h, 70 cases)according to CIT. Kaplan-Meier method is employed for estimating 1-year cumulative survival rate and multivariable Cox proportional hazard regression model for identifying independent risk factors of 1-year mortality.Results:No significant inter-group difference existed in the incidence of primary graft dysfunction grade Ⅲ within the first 72 h post-LTx(21.2% vs. 16.3%). The 30-day(90.2% vs. 94.3%)and 90-day(82.9% vs. 82.9%)survival rates are comparable between two groups. Similarly 1-year cumulative survival is also comparable between two groups (74.6% vs. 60.4%, Log-rank P=0.279). Multivariate Cox regression analysis indicated that prolonged CIT was not associated with an elevated risk of 1-year mortality( HR 0.691; 95% CI: 0.317~1.506). However, an absence of ECMO support during surgery( HR 3.562; 95% CI: 1.061~11.959)and postoperative mechanical ventilation for >3 days(HR 2.892; 95% CI: 1.387~6.031)elevate 1-year risk of mortality. Conclusions:Prolongation of CIT to 8~12 h has no adverse effect on the prognosis of recipients. Given a great scarcity of donor lungs and a growing number of LTx candidates, it is reasonable to accept prolonged CIT donor lungs for clinical LTx.

Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets.

Introduction: For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs. recipient NK cells. Methods: Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results: Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR+ T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion: Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx.

The Impact of Virtual Crossmatch on Cold Ischemic Times and Outcomes Following Kidney Transplantation.

BACKGROUND: Prolonged cold ischemic time (CIT) in deceased donor kidney transplantation (DDKT) has been associated with adverse graft outcomes. Virtual crossmatch (VXM) facilitates reliable prediction of crossmatch results based on the profile of human leukocyte antigen antibodies of the recipient and the donor in reduced time compared with a physical crossmatch (PXM). We hypothesized a shorter CIT since the implementation of the VXM in recipients of DDKT. METHODS: We conducted a retrospective cohort study of consecutive adult recipients of DDKT. The data were analyzed for differences in CIT before and after the implementation of VXM. RESULTS: After the exclusion of 59 recipients (age less than 18 years and/or CIT ≥ 20 hours), our study compared outcomes of 81 PXMs from February to June 2018 against 68 VXMs from February to June 2019. There were no statistical differences between groups based on donor age (P = .09), donor type (P = .38), kidney donor profile index (P = .43), or delayed graft function (P = .20). Recipients with VXM were older (58 vs 51 years, P = .002) and had a higher estimated post-transplant survival score (59% vs 46%, P = .01). The CIT was significantly lower for the VXM group (P = .04). CONCLUSION: Our study demonstrated a significantly shorter CIT with VXM in DDKT recipients. Our study was limited with small sample size, but the trend of increased graft survival with higher estimated post-transplant scores and older recipients is encouraging as the donor pool expands with marginal kidneys and national sharing.

Comparative Analysis of Risk Factors in Declined Kidneys from Donation after Brain Death and Circulatory Death.

Background and objectives: Kidneys from donation after circulatory death (DCD) are more likely to be declined for transplantation compared with kidneys from donation after brain death (DBD). The aim of this study was to evaluate characteristics in the biopsies of human DCD and DBD kidneys that were declined for transplantation in order to rescue more DCD kidneys. Materials and Methods: Sixty kidney donors (DCD = 36, DBD = 24) were recruited into the study and assessed using donor demographics. Kidney biopsies taken post cold storage were also evaluated for histological damage, inflammation (myeloperoxidase, MPO), von Willebrand factor (vWF) expression, complement 4d (C4d) deposition and complement 3 (C3) activation using H&E and immunohistochemistry staining, and Western blotting. Results: More DBD donors (16/24) had a history of hypertension compared with DCDs (8/36, p = 0.001). The mean warm ischemic time in the DCD kidneys was 12.9 ± 3.9 min. The mean cold ischemic time was not significantly different between the two groups of kidney donors (DBD 33.3 ± 16.7 vs. DCD 28.6 ± 14.1 h, p > 0.05). The score of histological damage and MPO, as well as the reactivity of vWF, C4d and C3, varied between kidneys, but there was no significant difference between the two donor types (p > 0.05). However, vWF reactivity might be an early indicator for loss of tissue integrity, while C4d deposition and activated C3 might be better predictors for histological damage. Conclusions: Similar characteristics of DCD were shown in comparison with DBD kidneys. Importantly, the additional warm ischemic time in DCD appeared to have no further detectable adverse effects on tissue injury, inflammation and complement activation. vWF, C4d and C3 might be potential biomarkers facilitating the evaluation of donor kidneys.

Effect of Donor Hepatic Steatosis on Ischemia Reperfusion Injury in Liver Transplant Recipient.

INTRODUCTION: Ischemia reperfusion injury (IRI) is an important complication of liver transplant (LT). The donor risk index, which does not incorporate steatosis, includes several variables known to impact on allograft survival. The purpose of this study was to report on donor liver allograft steatosis and its association with severity of IRI. AIM: The aim of this study was to determine the effect of type and grade of donor liver steatosis on the occurrence and severity of IRI in LT recipients. METHODS: This was an observational study conducted at a single center over a period of 37 months from July 2013 to August 2016. Liver biopsy was performed twice, initially at the time of procurement before graft perfusion for steatosis assessment. Steatosis was classified as microsteatosis (MiS) or macrosteatosis (MaS) with mild, moderate, or severe grade. Second biopsy for IRI assessment was taken before skin closure in death donor LT (DDLT) and at the time of transaminitis in postoperative period (<72 hrs) in living donor LT (LDLT). IRI was graded as per neutrophil infiltrate, apoptosis, and hepatocyte cell dropout. Prevalence of IRI and association steatosis was studied along with other factors. RESULTS: Among 53 subjects, 35 were DDLTs and 18 were LDLTs. All live donor grafts were restricted to <15% MaS and the deceased liver grafts had different type and degree of steatosis. In DDLTs, the association between occurrence of IRI and MaS was not statistically significant (P = 0.201). In DDLTs, the mild steatosis was not significantly associated with IRI. Death donor and ischemic time were significantly associated with IRI. Child's stage and MELD scores, gender, and age were not associated with risk of IRI. Severity of IRI is significantly associated with 3-month mortality (P = 0.001). CONCLUSION: In patients with mild steatosis, IRI does not correlate with steatosis. However, more patients with moderate and severe steatosis are needed to define the relationship of the two in this group of patients.

Clinical outcome of donor heart with prolonged cold ischemic time: A single-center study.

OBJECTIVES: Due to the shortage of donor pool, there has been a need for organs with prolonged cold ischemic time. This study aims to evaluate the short-term results of different cold ischemic times in orthotopic heart transplantation based on a single-center experience in China. METHODS: We retrospectively analyzed outcomes of the heart transplant patients from 1 January 2015 to 31 December 2017. The recipient population was divided into four groups. Group 1: cold ischemic time greater than 8 hours; group 2: the cold ischemic time between 6 and 8 hours; group 3: the cold ischemic time between 4 and 6 hours; and group 4: cold ischemic time less than 4 hours. Efficacy indicators included after transplant survival, infection rate, rejection rate, and complications. RESULTS: The four groups have similar donor and recipient baseline characteristics (P > .05). Cold ischemic time greater than 8 hours had more cardiopulmonary bypass (CPB) time (127.62 ± 50.23 minutes; P = .003), CPB-assist time (86.14 ± 36.74 minutes; P = .047), and higher intra-aortic balloon pump (IABP) usage rate postoperatively (47.36%; P = .010). Cold ischemic time greater than 8 hours witnessed a relatively higher mortality rate compared with the other three groups (P = .115, P = .078, and P = .114) during the 2-year follow-up. Survival rates of 1 and 2 years for the four groups were 78.95%, 87.13%, 87.32%, and 87.50% and 68.42%, 85.14%, 85.92%, and 83.93%, respectively. CONCLUSION: Cold ischemic time less than 8 hours can be reasonably applied to expand the heart transplantation donor pool. Cold ischemic time greater than 8 hours might result in longer CPB time, CPB-assist time, and higher IABP usage postoperatively. It might also affect the in-hospital and 2-years survival rate.

Repeat Biomarker Status in Breast Resection Specimens With Controlled Cold Ischemic Time.

OBJECTIVES: Current College of American Pathologists/American Society of Clinical Oncology guidelines recommend cold ischemic time (CIT) of 1 hour or less for breast specimens to preserve biomarker expression, although some publications support an acceptable CIT of 4 hours or less. We retrospectively evaluated changes in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from biopsy to resection specimens that were triaged to optimize CIT. METHODS: We identified breast resection specimens collected after institutional implementation of a triage protocol. Clinicopathologic features were assessed. RESULTS: In total, 295 excisions had a prior malignant diagnosis, with CIT of 4 hours or less and repeat ER, PR, and/or HER2; 230 (78%) had CIT of 1 hour or less, and 65 (22%) had CIT of more than 1 hour but 4 hours or less. Categorical change was seen in 10 (17.9%) of 56 with repeated ER/PR and 38 (13.3%) of 285 with repeated HER2 (of which five [1.8%] had meaningful change). CONCLUSIONS: When CIT is optimized, a meaningful change in biomarker expression is infrequent. This study supports that when specimens are appropriately triaged, CIT of 4 hours or less may be acceptable.

Therapeutic Strategies of Kidney Transplant Ischemia Reperfusion Injury: Insight From Mouse Models.

Ischemia/reperfusion injury (IRI) is inherent to all transplanted organs and is adversely associated with early renal graft function and graft longevity. Despite the progress in immunosuppressive regimens and perioperative care, no FDA-approved treatment for kidney transplant IRI is available to date. In recent years, by utilizing the modified and clinically-relevant mouse models of kidney transplantation (KTx) in which extended IRI is induced by the prolonged warm or cold ischemic time, studies have identified several potential therapeutic approaches for KTx IRI, including the hormone supplement, promoting tubular repair and regeneration, and targeting complement system, inflammation, and necroptosis. This review describes some of the lessons learned from mouse models of KTx with regard to factors that influence the severity of transplant IRI and the potential therapeutic targets.

The impact of the angioplasty of the renal artery and cold ischemia time in kidney transplantation on graft function.

The aim of this study was to analyze the benefit of the patients after renal transplantation with an assessment of the significance of different surgical techniques in patients with renal transplantation (not only from the dead but also the living donors) with multiple arteries. 457 patients with end stage renal disease (ESRD) in the treatment using the extracorporeal elimination method (haemodialysis, or peritoneal dialysis), who in the period from 2005 to 2015 had a kidney transplant were included in our retrospective study. Our results confirm that the patients after kidney transplantation with cold ischemia time more than 12 hours have 2.5 times higher risk of delayed onset, possibly failure of graft function compared to those with cold ischemia time less than 12 hours. This confirms our experience that the best option for the patient to achieve a stable graft function with long-term perspective is cold ischemia time of less than 12 hours and the realisation of renal artery angioplasty. In this case, the risk of delayed onset of transplanted kidney function or graft failure decreases 4.5 times compared to the respondents with cold ischemia time more than 12 hours without carrying out arterial angioplasty (Tab. 1, Fig. 4, Ref. 16).

Dopamine in transplantation: Written off or comeback with novel indication?

Renal-dose dopamine has fallen out of favor in the intensive care unit (ICU) during past years due to its ineffectiveness to prevent impending or to ameliorate overt renal failure in the critically ill. By contrast, growing evidence indicates that low-dose dopamine administered to the stable organ donor after brain death confirmation improves the clinical course of transplanted organs after kidney and heart transplantation. Ensuring a thorough monitoring for potential circulatory side effects, employment of dopamine at a dose of 4 µg/kg/min is safe in the deceased donor. Among recipients, the advantageous effect is easy to achieve, inexpensive, and devoid of adverse side effects. The mode of action relies on dopamine's propensity to mitigate injury in various cell systems from isolated transplantable organs under cold storage conditions. The present review article summarizes the clinical evidence of dopamine donor pretreatment in solid organ transplantation and focuses on the underlying molecular mechanisms of cellular protection. Introducing the routine use of low-dose dopamine for the management of the brain-dead donor in the ICU before procurement provides an evidence-based strategy to improve graft outcome after kidney transplantation without conferring harm to non-renal grafts, namely to livers and hearts, in cases of multi-organ donation.

A rapid triage protocol to optimize cold ischemic time for breast resection specimens.

Prolonged time from specimen excision to adequate formalin exposure, or cold ischemic time (CIT), negatively impacts estrogen receptor (ER), progesterone receptor (PR) and HER-2 biomarker studies routinely performed on breast specimens. Current guidelines recommend CIT of ≤1 h. Since formalin penetrates resections slowly, optimal fixation requires incision. We evaluated the efficacy of a rapid triage protocol developed to optimize CIT. We identified 2821 specimens: 650 (23.0%) excisional biopsies (EB), 1051 (37.3%) lumpectomies, and 1120 (39.7%) mastectomies. CIT was available for 2362 (83.7%), with 1845 (78.1%) ≤1 h and 2323 (98.3%) ≤4 h. IHC was performed in 533/2821 (18.9%) and was associated with lumpectomy and mastectomy procedures when compared to EB. However, IHC was also performed on 11.1% (72/650) of EB specimens despite EB being significantly less likely to have CIT recorded (468/650; 72% for EB vs. 1894/2171; 87.2% for lumpectomies/mastectomies). Our study highlights the need for rapid triage of breast resections with known or suspected malignant diagnoses and outlines our procedure for optimizing CIT. Additionally, we advocate treating ALL breast resections as having the potential of being malignant and requiring biomarker studies for which optimal CIT is of great importance.

Effect of airplane transport of donor livers on post-liver transplantation survival.

AIM: To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS: A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. RESULTS: One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance (r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver (P = 0.027). CONCLUSION: Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

Donor Factors Including Donor Risk Index Predict Fibrosis Progression, Allograft Loss, and Patient Survival following Liver Transplantation for Hepatitis C Virus.

BACKGROUND: The utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients. METHODS: HCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis. RESULTS: Of 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (P = 0.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7. CONCLUSIONS: (1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.

Kidney donor risk index is a good prognostic tool for graft outcomes in deceased donor kidney transplantation with short, cold ischemic time.

BACKGROUND: We performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one-yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero-time kidney biopsies. METHODS: We reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero-time kidney biopsy was performed in 196 patients, and histologic score was assessed. RESULTS: Median follow-up duration was 46 months. Forty-two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one-yr estimations of glomerular filtration rate (eGFR) (R(2) = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01-6.87). However, higher histologic score was not associated with a higher risk of graft failure. CONCLUSION: KDRI has greater predictive value for short-term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.