The latest medical research on Transplant

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Urgent Liver Transplantation for Acute Liver Failure in Pregnant Women: The Optimum Timing for Delivery.

Transplantation

The occurrence of acute liver failure (ALF) in pregnant women due to an etiology unrelated to pregnancy (pregALF) that leads to liver transplantation (LT) has rarely been reported. The objective was to report the outcome of pregnant women and fetus and propose a strategy for the timing of delivery and of LT in these patients.

Five consecutive pregnant patients with ALF were admitted to our center between 1986 and 2018 and underwent an LT. A systematic review of case reports concerning patients with pregALF who underwent LT was extracted from the literature.

Three with gestational ages (GA) at admission of 15, 22, and 31 weeks of gestation (WG) were transplanted after delivery (n = 1) or intrauterine demise (n = 2) and 2 with GA of 16 and 23 WG before delivery. One infant survived in each group. Among the 32 cases published previously, 11 (34%) had been transplanted after delivery (median GA:31 [28-33]); 10 of these 11 infants were alive at birth. The other 21 mothers were transplanted before delivery (GA:21 WG [18-22]). The median GA at delivery was 30 WG [27.75-37]. Twelve of 21 infants were alive at birth. One-year survival among the ALF patients in our series and in the literature was 100%. Overall, the perinatal survival rate was low (64.8%).

In pregnant patients presenting with ALF not related to the pregnancy, the LT lifesaving procedure had an excellent outcome. Overall, 65% of the infants were alive at delivery with major mortality in those fetus <22 WG despite continued pregnancy.

Impact of Older Donor Age on Recipient and Graft Survival After LDLT: The US Experience.

Transplantation

The impact of selecting older donors for living donor liver transplantation (LDLT) in the United States is incompletely studied, particularly in light of the recent expansion of LDLT nationally.

Adult LDLTs from January 01, 2005 to December 31, 2019 were identified using the United Network for Organ Sharing database. Multivariable Cox models evaluated living donor (LD) age as a predictor of LDLT recipient and graft survival. The impact of increasing donor age on recipient outcomes was compared between LD and deceased donor recipients. Donor postoperative outcomes were evaluated.

There were 3539 LDLTs at 65 transplant centers during the study period. Despite the recent expansion of LDLT, the proportion of LDs aged ≥50 y was stable. There were no clinically significant differences in recipient or donor characteristics by LD age group. LD age ≥50 y was associated with an adjusted hazard ratio of 1.49 (P = 0.012) for recipient survival and 1.61 (P < 0.001) for graft survival (vs LDs aged 18-29 y). The negative impact of increasing donor age on graft survival was more profound after LDLT than deceased donor liver transplantation (interaction P = 0.019). There was a possible increased rate of early donor biliary complications for donors >55 y (7.1% versus 3.1% for age <40 y; P = 0.156).

Increasing LD age is associated with decreased recipient and graft survival, although older donors still largely yield acceptable outcomes. Donor outcomes were not clearly impacted by increasing age, though this warrants further study.

Impact of Donor Liver Macrovesicular Steatosis on Deceased Donor Yield and Posttransplant Outcome.

Transplantation

The Scientific Registry of Transplant Recipients (SRTR) had not traditionally considered biopsy results in risk-adjustment models, yet biopsy results may influence outcomes and thus decisions regarding organ acceptance.

Using SRTR data, which includes data on all donors, waitlisted candidates, and transplant recipients in the United States, we assessed (1) the impact of macrovesicular steatosis on deceased donor yield (defined as number of livers transplanted per donor) and 1-y posttransplant graft failure and (2) the effect of incorporating this variable into existing SRTR risk-adjustment models.

There were 21 559 donors with any recovered organ and 17 801 liver transplant recipients included for analysis. Increasing levels of macrovesicular steatosis on donor liver biopsy predicted lower organ yield: ≥31% macrovesicular steatosis on liver biopsy was associated with 87% to 95% lower odds of utilization, with 55% of these livers being discarded. The hazard ratio for graft failure with these livers was 1.53, compared with those with no pretransplant liver biopsy and 0% to 10% steatosis. There was minimal change on organ procurement organization-specific deceased donor yield or program-specific posttransplant outcome assessments when macrovesicular steatosis was added to the risk-adjustment models.

Donor livers with macrovesicular steatosis are disproportionately not transplanted relative to their risk for graft failure. To avoid undue risk aversion, SRTR now accounts for macrovesicular steatosis in the SRTR risk-adjustment models to help facilitate use of these higher-risk organs. Increased recognition of this variable may also encourage further efforts to standardize the reporting of liver biopsy results.

Dynamics of Human Anelloviruses in Plasma and Clinical Outcomes Following Kidney Transplantation.

Transplantation

Torque teno virus, the major member of the genus Alphatorquevirus, is an emerging biomarker of the net state of immunosuppression after kidney transplantation. Genetic diversity constitutes a main feature of the Anelloviridae family, although its posttransplant dynamics and clinical correlates are largely unknown.

The relative abundance of Alphatorquevirus, Betatorquevirus, and Gammatorquevirus genera was investigated by high-throughput sequencing in plasma specimens obtained at various points during the first posttransplant year (n = 91 recipients). Total loads of all members of the Anelloviridae family were also quantified by an "in-house" polymerase chain reaction assay targeting conserved DNA sequences (n = 195 recipients). In addition to viral kinetics, clinical study outcomes included serious infection, immunosuppression-related adverse event (opportunistic infection and cancer)' and acute rejection.

Alphatorquevirus DNA was detected in all patients at every point, with an increase from pretransplantation to month 1. A variable proportion of recipients had detectable Betatorquevirus and Gammatorquevirus at lower frequencies. At least 1 change in the predominant genus (mainly as early transition to Alphatorquevirus predominance) was shown in 35.6% of evaluable patients. Total anelloviruses DNA levels increased from baseline to month 1, to peak by month 3 and decrease thereafter, and were higher in patients treated with T-cell depleting agents. There was a significant albeit weak-to-moderate correlation between total anelloviruses and TTV DNA levels. No associations were found between the predominant Anelloviridae genus or total anelloviruses DNA levels and clinical outcomes.

Our study provides novel insight into the evolution of the anellome after kidney transplantation.

Outcomes of Nonstandard Donor Kidney Transplants in Recipients Aged 70 Years or More: A Single-Center Experience.

Exp Clin Transplant

There is a global increase in the prevalence of end-stage kidney disease among the elderly. As a result, more elderly recipients are being considered for kidney transplants. Because of the scarcity of donor organs, such patients are more likely to receive transplants from nonstandard donor kidneys.Here, we examined the outcomes of kidney transplants with a nonstandard donor allograftin recipients ≥70 years of age.

Records of patients who received transplants at a single UK centerfrom April 1, 2015, through March 31, 2021, were retrospectively analyzed to identify those who were ≥70 years old at the time of surgery. Outcomes ofthose who received a kidney transplantfrom a nonstandard donor (group 1) were compared to those who received a kidney transplant from a standard criteria donor or living donor (group 2).

During the study period, of 670 kidney transplant procedures, 67 recipients (10%) were ≥70 years of age at the time of surgery, with 54 (80.6%) identified in group 1 and 13 (19.4%) identified in group 2. Cold ischemia time (P = .001) and incidence of delayed graft function (P = .044) were significantly higherin group 1. Duration of graft survival atthe end of follow-up was not different between the groups (log rank = 0.218), butthe mean serum creatinine values at 2 years (P = .016) and 3 years (P = .048) years were significantly higherin group 1. Patients in group 1 had shorter survival time (log rank = 0.037).

Nonstandard donor kidneys should be used cautiously in elderly recipients as patient survival was shown to be comparatively poor compared with elderly recipients who received a kidney transplant from a standard criteria donor or a living donor.

Excess Mortality Among Solid Organ Transplant Recipients in the United States During the COVID-19 Pandemic.

Transplantation

The COVID-19 pandemic is the first sustained respiratory disease pandemic to arise since the start of solid organ transplantation (SOT). Prior studies have demonstrated that SOT recipients are at greater risk for severe complications of infection and are less likely to respond to vaccination.

The Scientific Registry of Transplant Recipients Standard Analysis Files was used to assess the cumulative excess mortality in SOT recipients during the first 20 mo of the pandemic.

Compared with excess mortality rates in the US population (25.9 deaths/10 000; confidence interval [CI], 10.9-41.1), the excess mortality per 10 000 was higher in all SOT groups: kidney (188.5; CI, 150.7-225.6), lung (173.6; CI, 17-334.7), heart (123.7; CI, 56-191.4), and liver (105.1; CI, 64.6-146). The higher rates persisted even with attempts to control for population age structure and renal allograft failure. Excess mortality was also higher in Black (236.8; CI, 186.1-287) and Hispanic (256.9; CI, 208.1-305.2) organ recipients compared with other racial and ethnic groups in the Scientific Registry of Transplant Recipients and compared with the Black and Hispanic populations in the United States. Conclusions. Studies of excess mortality provide insight into the health and survival of specialized populations like SOT recipients during major health events like the COVID-19 pandemic.

Length of Alcohol Abstinence Predicts Posttransplant Delirium in Living Donor Liver Transplant Recipients with Alcoholic Cirrhosis.

Exp Clin Transplant

History of alcohol abuse is a predictive factor for posttransplant delirium. We aimed to investigate whether preoperative abstinence was associated with posttransplant delirium in liver transplant recipients with alcohol-related cirrhosis.

From January 2014 to December 2019, 84 patients with alcohol-related cirrhosis who received living donor liver transplant were retrospectively reviewed and divided into a delirium group (n = 46, 54.8%) and a nondelirium group (n = 38, 45.2%) using the Richmond Agitation- Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit.

In the delirium group versus the nondelirium group, patients were more likely to have preoperative hepatic encephalopathy (58.7% vs 31.6%; P = .013), more likely to have higher Model for End-Stage Liver Disease scores (27.05 ± 10.56 vs 18.85 ± 7.96; P < .001), less likely to have preoperative alcohol abstinence (43.5% vs 68.4%%; P = .022), had longer duration of mechanical ventilation (7.57 ± 7.82 vs 2.50 ± 5.96 days; P = .001), and had longer stays in the intensive care unit (14.85 ± 15.01 vs 8.84 ± 7.84 days; P = .021) and in the hospital (37.89 ± 18.85 vs 27.15 ± 10.43 days; P = .002). Multivariate analysis revealed that preoperative alcohol abstinence (odds ratio 4.953; 95% CI, 1.519-16.152; P = .008) was a significant predictor and that more patients had abstinence durations <3 months (60.9% vs 34.2%; P = .048) in the delirium group.

A high incidence of posttransplant delirium in liver transplant recipients with alcohol- related cirrhosis was associated with preoperative abstinence. Abstinence >6 months before living donor liver transplant is suggested to reduce the risk of posttransplant delirium.

Clamping of the Aortic Arch Vessels During Normothermic Regional Perfusion Does Not Negatively Affect Donor Cardiac Function in Donation After Circulatory Death.

Transplantation

The hemodynamic effects of aortic arch vessel (AAV) clamping during normothermic regional perfusion (NRP) in donation after circulatory death is unknown. We investigated effects of AAV clamping during NRP compared with no clamping in a porcine model.

In 16 pigs, hemodynamic parameters were recorded including biventricular pressure-volume measurements and invasive blood pressure. Additionally, blood gas parameters and inflammatory cytokines were used to assess the effect of AAV clamping. The animals were centrally cannulated for NRP, and baseline measurements were obtained before hypoxic circulatory arrest was induced by halting mechanical ventilation. During an 8-min asystole period, the animals were randomized to clamp (n = 8) or no-clamp (n = 8) of the AAV before commencement of NRP. During NRP, circulation was supported with norepinephrine (NE) and dobutamine. After 30 min of NRP, animals were weaned and observed for 180 min post-NRP.

All hearts were successfully reanimated and weaned from NRP. The nonclamp groups received significantly more NE to maintain a mean arterial pressure >60 mm Hg during and after NRP compared with the clamp group. There were no between group differences in blood pressure or cardiac output. Pressure-volume measurements demonstrated preserved cardiac function' including ejection fraction and diastolic and systolic function. No between group differences in inflammatory markers were observed.

AAV clamping did not negatively affect donor cardiac function or inflammation after circulatory death and NRP. Significantly less NE was used to support in the clamp group than in the nonclamp group.

A First Case Report of Cytomegalovirus Infection Presenting With Perianal Fistula and Abscess Formation in a Kidney Transplant Recipient.

Exp Clin Transplant

Cytomegalovirus infection after transplant has been dramatically reduced in the modern era with improved understanding of immunosuppression and per...

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases.

Transplantation

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activ...

Predicting Early Allograft Function After Normothermic Machine Perfusion.

Transplantation

Normothermic ex situ liver perfusion is increasingly used to assess donor livers, but there remains a paucity of evidence regarding criteria upon which to base a viability assessment or criteria predicting early allograft function.

Perfusate variables from livers undergoing normothermic ex situ liver perfusion were analyzed to see which best predicted the Model for Early Allograft Function score.

One hundred fifty-four of 203 perfused livers were transplanted following our previously defined criteria. These comprised 84/123 donation after circulatory death livers and 70/80 donation after brain death livers. Multivariable analysis suggested that 2-h alanine transaminase, 2-h lactate, 11 to 29 mmol supplementary bicarbonate in the first 4 h, and peak bile pH were associated with early allograft function as defined by the Model for Early Allograft Function score. Nonanastomotic biliary strictures occurred in 11% of transplants, predominantly affected first- and second-order ducts, despite selection based on bile glucose and pH.

This work confirms the importance of perfusate alanine transaminase and lactate at 2-h, as well as the amount of supplementary bicarbonate required to keep the perfusate pH > 7.2, in the assessment of livers undergoing perfusion. It cautions against the use of lactate as a sole indicator of viability and also suggests a role for cholangiocyte function markers in predicting early allograft function.

Infection calls for thrombosis: Fact or superstition?

Journal of Artificial Intelligence Research

Despite all the efforts, pump thrombosis and thromboembolic complications still remain among the most dreadful complications after long-term ventri...