Outcomes of kidneys used for transplantation: an analysis of survival and function.

Introduction: Kidney transplant recipients expect to survive the procedure with sufficient renal function for reliable dialysis freedom. Methods: Transplant outcomes (survival and estimated renal function) were assessed after live and deceased donor transplantation from the US national database. Outcomes were stratified by age (donor and recipient) and donor type. Results: Aggregate recipient outcomes were better transplanting living vs deceased donated kidneys. However, when stratified by the one-year renal function (within KDIGO CKD stage stratifications), surviving recipients had clinically similar dialysis-freedom, irrespective of donor type or age. The major outcome differences for recipients of age-stratified live and deceased kidneys was 1) the increasing frequency of one-year graft failures and 2) the increasing likelihood of severely limited renal function (CKD 4/5) with advancing donor age. Over 30% of recipients of deceased kidneys >65 years had either one-year graft failure or severely limited renal function contrasted to less than 15% of recipients of live kidneys aged >65 years. Conclusions: Evolving techniques to reduce adverse events after urgent vs elective procedures, plus improved transplant outcome predictability with increased-age deceased donor kidneys using advanced predictive analytics (using age-stratified live kidney transplantation outcomes as a relevant reference point) should facilitate similar kidney transplant outcomes, irrespective of donor type.

Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium.

BACKGROUND: In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. METHODS: We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 µm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. RESULTS: In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. CONCLUSIONS: Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Essential Fatty Acid Deficiency is Common after Total Pancreatectomy and Islet AutoTransplantation.

OBJECTIVES: Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. METHODS: We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥ 0.05 if <18 years old, or ≥ 0.038 if ≥18 years old. RESULTS: Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥ 3 years. At 1 year post-TPIAT, older age at transplant (p = 0.03), being an adult versus a child (p = 0.0024), and obstructive etiology (p = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1 year post-TPIAT vs. 46% of adults. ALA levels were lower with lower BMI at transplant (p = 0.011). EFAD was associated with the presence of other intestinal diseases (p < 0.0001). CONCLUSIONS: One-third of individuals had EFAD 1 year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors.

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation.

Background: Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. Methods: In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of ß-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes. Results: Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler "clinically feasible" model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively). Conclusions: Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.

Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs.

Aging of the world population significantly impacts healthcare globally and specifically, the field of transplantation. Together with end-organ dysfunction and prolonged immunosuppression, age increases the frequency of comorbid chronic diseases in transplant candidates and recipients, contributing to inferior outcomes. Although the frequency of death increases with age, limited use of organs from older deceased donors reflects the concerns about organ durability and inadequate function. Cellular senescence (CS) is a hallmark of aging, which occurs in response to a myriad of cellular stressors, leading to activation of signaling cascades that stably arrest cell cycle progression to prevent tumorigenesis. In aging and chronic conditions, senescent cells accumulate as the immune system's ability to clear them wanes, which is causally implicated in the progression of chronic diseases, immune dysfunction, organ damage, decreased regenerative capacity, and aging itself. The intimate interplay between senescent cells, their proinflammatory secretome, and immune cells results in a positive feedback loop, propagating chronic sterile inflammation and the spread of CS. Hence, senescent cells in organs from older donors trigger the recipient's alloimmune response, resulting in the increased risk of graft loss. Eliminating senescent cells or attenuating their inflammatory phenotype is a novel, potential therapeutic target to improve transplant outcomes and expand utilization of organs from older donors. This review focuses on the current knowledge about the impact of CS on circulating immune cells in the context of organ damage and disease progression, discusses the impact of CS on abdominal solid organs that are commonly transplanted, and reviews emerging therapies that target CS.

Lumped parameter liver simulation to predict acute haemodynamic alterations following partial resections.

Partial liver resections are routinely performed in living donor liver transplantation and to debulk tumours in liver malignancies, but surgical decisions on vessel reconstruction for adequate inflow and outflow are challenging. Pre-operative evaluation is often limited to radiological imaging, which fails to account for post-resection haemodynamic alterations. Substantial evidence suggests post-surgical increase in local volume flow rate enhances shear stress, signalling hepatic regeneration, but excessive shear stress has been postulated to result in small for size syndrome and liver failure. Predicting haemodynamic alterations throughout the liver is particularly challenging due to the dendritic architecture of the vasculature, spanning several orders of magnitude in diameter. Therefore, we developed a mathematical lumped parameter model with realistic heterogeneities capturing inflow/outflow of the human liver to simulate acute perfusion alterations following surgical resection. Our model is parametrized using clinical measurements, relies on a single free parameter and accurately captures established perfusion characteristics. We quantify acute changes in volume flow rate, flow speed and wall shear stress following variable, realistic liver resections and make comparisons with the intact liver. Our numerical model runs in minutes and can be adapted to patient-specific anatomy, providing a novel computational tool aimed at assisting pre- and intra-operative surgical decisions for liver resections.

Characteristics and Outcomes of De Novo Genitourinary Malignancy in Solid Organ Transplant Recipients at the University of Minnesota.

BACKGROUND: Studies examining outcomes of genitourinary malignancy (GU) in the solid organ transplant (SOT) population predominantly focus on renal transplant recipients and consist of relatively small cohorts. We aimed to expand knowledge of the characteristics and outcomes of de novo GU malignancies in all patients with SOT at a large tertiary center. METHODS: The SOT database was queried for recipients with de novo bladder, renal cell, and prostate malignancy, and a retrospective chart review was performed. Descriptive statistics and Kaplan-Meier survival estimates were calculated. Cox proportional hazards regression was used for multivariate modeling of predictive factors in the development of GU malignancy. RESULTS: Solid organ transplant recipients with de novo bladder malignancy comprised 64.3% with high grade and 38.1% with advanced stage (≥T2) disease at initial diagnosis. Only 3.7% of patients with de novo renal cell carcinoma presented with metastatic disease, and 13.6% with localized disease developed recurrences. The most common stage in de novo prostate cancer patients was pT3 (52.2%). Kaplan-Meier estimates (95% CI) for 5-year overall (OS) and cancer-specific survival (CSS) were 44.12% (31.13-62.52) and 80.80% (68.85-94.81) for bladder, 78.90% (68.93-90.30) and 96.61% (92.10-100.00) for renal cell, and 81.18% (72.01-91.51) and 96.16% (90.95-100.00) for prostate cancer, respectively. Age at transplant and time from transplant to cancer diagnosis were predictive of de novo bladder cancer OS (P = .042 and .021, respectively). CONCLUSION: To our knowledge, this is the largest single-center cohort examined for GU malignancy after SOT. Bladder and renal cell cancer had worse OS but similar CSS as historical rates for nontransplant patients. De novo prostate cancer had similar CSS.

Recipient and kidney graft outcomes of deceased donors with human immunodeficiency virus in the United States.

BACKGROUND: The HIV Organ Policy Equity (HOPE) act afforded transplantation of organs from donors who have HIV. Herein we compared the long-term outcomes of recipients with HIV by donor HIV testing status. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all primary adult kidney transplant recipients who were HIV-positive between 1/1/16-12/31/21. Recipients were grouped into three cohorts according to the donor HIV status based on antibody (Ab) and nucleic acid testing (NAT): Donor Ab-/NAT- (n = 810), Donor Ab+ /NAT- (n = 98), and Donor Ab+/NAT+ (n = 90). We compared recipient and death-censored graft survival (DCGS) by donor HIV testing status using Kaplan-Meier curves and Cox proportional hazards regression, censored at 3 years posttransplant. Secondary outcomes were delayed graft function (DGF) and the following 1-year outcomes: acute rejection, re-hospitalization, and serum creatinine. RESULTS: In Kaplan-Meier analyses, patient survival and DCGS were similar by donor HIV status (log rank p = .667; log rank p = .388). DGF occurred more frequently in donors with HIV Ab-/NAT- testing compared with Ab+/NAT- or Ab+/NAT+ testing (38.0% vs. 28.6% vs. 26.7%, p = .028). Average dialysis time before transplant was twice as long for recipients who received organs from donors with Ab-/NAT- testing (p < .001). Acute rejection, re-hospitalization and serum creatinine at 12 months did not differ between the groups. CONCLUSIONS: Patient and allograft survival for recipients living with HIV remains comparable irrespective of donor HIV testing status. Utilizing kidneys from deceased donors with HIV Ab+/NAT- or Ab+/NAT+ testing shortens dialysis time prior to transplant.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium.

BACKGROUND AND AIMS: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. METHODS: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. RESULTS: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. CONCLUSIONS: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model.

Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use "nanowarming," which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.

CT-derived psoas muscle area and density are associated with length of stay and discharge disposition after liver transplantation.

BACKGROUND & AIMS: Prolonged length of stay (LOS) and discharge disposition following liver transplantation are associated with postoperative complications and increased healthcare utilization. This study evaluated the relationship between CT-derived psoas muscle measurements and hospital LOS, intensive care unit (ICU) LOS, and discharge disposition after liver transplant. The psoas muscle was chosen given its ease of measurement with any radiological software. A secondary analysis assessed the relationship between the American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics (ASPEN/AND) malnutrition diagnosis criteria and CT-derived psoas muscle measures. METHODS: CT-derived measures of psoas muscle density (mHU) and cross-sectional area at the level of the third lumbar vertebrae were obtained from preoperative CT scans of liver transplant recipients. Cross-sectional area measures were corrected for body size to generate a psoas area index variable (cm2/m2; PAI). RESULTS: Each 1-unit increase in PAI was associated with a reduced hospital LOS of 4 days (R2 = 0.07). Each 5-unit increase in mean Hounsfield units (mHU) was associated with a reduced hospital and ICU LOS of 5 and 1.6 days, respectively (R2 = 0.22 and 0.14, respectively). Mean PAI and mHU were higher in patients who discharged to home. PAI was reasonably identified through ASPEN/AND malnutrition criteria, but there was no difference in mHU between those with and without malnutrition. CONCLUSION: Measures of psoas density were associated with both hospital and ICU LOS and discharge disposition. PAI was associated with hospital LOS and discharge disposition. CT-derived measures of psoas density may be a valuable complement to preoperative liver transplant nutrition assessment using traditional ASPEN/AND malnutrition criteria.

Predicting older-donor kidneys' post-transplant renal function using pre-transplant data.

This paper provides a methodology for predicting post-transplant kidney function, that is, the 1-year post-transplant estimated Glomerular Filtration Rate (eGFR-1) for each donor-candidate pair. We apply customized machine-learning algorithms to pre-transplant donor and recipient data to determine the probability of achieving an eGFR-1 of at least 30 ml/min. This threshold was chosen because there is insufficient survival benefit if the kidney fails to generate an eGFR-1 ≥ 30 ml/min. For some donor-candidate pairs, the developed algorithm provides highly accurate predictions. For others, limitations of previous transplants' data results in noisier predictions. However, because the same kidney is offered to many candidates, we identify those pairs for whom the predictions are highly accurate. Out of 6977 discarded older-donor kidneys that were a match with at least one transplanted kidney, 5282 had one or more identified candidate, who were offered that kidney, did not accept any other offer, and would have had ≥80% chance of achieving eGFR-1 ≥ 30 ml/min, had the kidney been transplanted. We also show that transplants with ≥80% chance of achieving eGFR-1 ≥ 30 ml/min and that survive 1 year have higher 10-year death-censored graft survival probabilities than all older-donor transplants that survive 1 year (73.61% vs. 70.48%, respectively).

Novel 3D-printed foot orthoses with variable hardness: A comfort comparison to traditional orthoses.

Custom foot orthoses are used to treat a variety of foot pathologies. However, orthotic production requires significant hands-on fabrication time and expertise to produce orthoses that are both comfortable and effective. This paper introduces a novel 3D printed orthosis and fabrication method that utilizes custom architectures to produce variable-hardness regions. These novel orthoses are compared to traditionally fabricated orthoses during a 2-week user comfort study. Twenty (n = 20) male volunteers underwent orthotic fitting for both traditional and 3D-printed foot orthoses prior to engaging in treadmill walking trials and 2 weeks of wear. Each participant undertook a regional comfort, acceptance, and comparison analysis of the orthoses at three time points throughout the study (0, 1, and 2 weeks). Both the 3D-printed and the traditionally fabricated foot orthoses demonstrated statistically significant increases in comfort when compared to the factory fabricated shoe insert. Additionally, the two orthosis groups were not significantly different from each other in comfort rankings both regionally and overall at any time point. The similar comfort achieved by the 3D-printed orthosis to the traditionally fabricated orthosis after 7 days and 14 days emphasizes the potential of the future use of the more reproducible and adaptable 3D-printed orthosis manufacturing methodology.

Immunology of the transplanted cryopreserved kidney.

Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.

A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.

BACKGROUND: In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence. METHODS: We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT. RESULTS: We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females. CONCLUSION: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment. CLINICAL TRIAL NOTATION: This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).

Good Long-Term Outcome Following Liver Transplant in a Patient With Common Variable Immunodeficiency Syndrome Despite Multiple Infections and Recurrent Nodular Regenerative Hyperplasia.

Common variable immunodeficiency can be associated with various hepatic conditions, the most common being nodular regenerative hyperplasia. Multiple cases of liver transplant in adults with common variable immunodeficiency have been reported. Here, we report a 51-year-old man with common variable immunodeficiency and noncirrhotic portal hypertension due to nodular regenerative hyperplasia who underwent liver transplant. The patient received tacrolimus/steroid immunosuppression and remained rejection free; however, he developed cytomegalovirus infection, disseminated nocardiosis, Pseudomonas pneumonia, and Clostridioides difficile- associated colitis. All infections were successfully managed. The graft was well functioning after 18 months; however, alkaline phosphatase remained elevated and a liver biopsy showed evidence of recurrent nodular regenerative hyperplasia. The patient was started on a steroid taper, which led to normalization of the alkaline phosphatase. Two years later, a repeat biopsy confirmed recurrent nodular regenerative hyperplasia. Immunosuppression was kept low, and intravenous immunoglobulin infusions were continued. More than 10 years later, the patient is alive with a functioning graft. This case emphasizes that intensified prophylaxis for infections and less intense immunosuppression may be strategies to enable long-term survival in liver transplant recipients with common variable immunodeficiency and nodular regenerative hyperplasia relapse despite recently reported poor outcomes in this patient population.

Current practice and novel approaches in organ preservation.

Organ transplantation remains the only treatment option for patients with end-stage organ failure. The last decade has seen a flurry of activity in improving organ preservation technologies, which promise to increase utilization in a dramatic fashion. They also bring the promise of extending the preservation duration significantly, which opens the doors to sharing organs across local and international boundaries and transforms the field. In this work, we review the recent literature on machine perfusion of livers across various protocols in development and clinical use, in the context of extending the preservation duration. We then review the next generation of technologies that have the potential to further extend the limits and open the door to banking organs, including supercooling, partial freezing, and nanowarming, and outline the opportunities arising in the field for researchers in the short and long term.