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.

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.

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).

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.

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.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Intraportal Islet Autotransplantation Independently Improves Quality of Life After Total Pancreatectomy in Patients With Chronic Refractory Pancreatitis.

OBJECTIVE: To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. METHODS: TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. RESULTS: Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. CONCLUSIONS: QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.

Surgical approach and short-term outcomes in adults and children undergoing total pancreatectomy with islet autotransplantation: A report from the Prospective Observational Study of TPIAT.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT. CONCLUSIONS: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.

Early Clostridioides difficile infection characterizations, risks, and outcomes in allogeneic hematopoietic stem cell and solid organ transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo-HCT) and solid organ transplantation (SOT). METHODS: We retrospectively analyzed risk factors and outcomes of CDI occurring within 30 days of transplant. RESULTS: Between March 2010 and June 2015, 466 allo-HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8-13) and 4% (3-5), following allo-HCT and SOT, respectively (p < .01), occurring at a median (range) 7.5 days (1-30) and 11 (1-30), respectively (p = .18). In multivariate analysis, fluoroquinolones use within 14 days pre-transplantation was a risk factor for CDI following allo-HCT (HR 4.06 [95% CI 1.31-12.63], p = .02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 [95% CI 1.31-6.98]) for lung and 3.90 (1.58-9.63) for heart and heart/kidney transplant, p = .02. Compared with no-CDI patients, the length of stay (LOS) was prolonged in both allo-HCT (35 days [19-141] vs. 29 [13-164], p < .01) and SOT with CDI (16.5 [4-101] vs. 7 [0-159], p < .01), though not directly attributed to CDI. In allo-HCT, severe acute graft-versus-host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p = .01) and most aGVHD (87.5%) followed CDI. Non-relapse mortality or overall survival, not attributed to CDI, were also similar in both allo-HCT and SOT. CONCLUSIONS: Early post-transplant CDI is frequent, associated with fluoroquinolones use in allo-HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo-HCT.

Ten years of donor-derived disease: A report of the disease transmission advisory committee.

Despite clinical and laboratory screening of potential donors for transmissible disease, unexpected transmission of disease from donor to recipient remains an inherent risk of organ transplantation. The Disease Transmission Advisory Committee (DTAC) was created to review and classify reports of potential disease transmission and use this information to inform national policy and improve patient safety. From January 1, 2008 to December 31, 2017, the DTAC received 2185 reports; 335 (15%) were classified as a proven/probable donor transmission event. Infections were transmitted most commonly (67%), followed by malignancies (29%), and other disease processes (6%). Forty-six percent of recipients receiving organs from a donor that transmitted disease to at least 1 recipient developed a donor-derived disease (DDD). Sixty-seven percent of recipients developed symptoms of DDD within 30 days of transplantation, and all bacterial infections were recognized within 45 days. Graft loss or death occurred in about one third of recipients with DDD, with higher rates associated with malignancy transmission and parasitic and fungal diseases. Unexpected DDD was rare, occurring in 0.18% of all transplant recipients. These findings will help focus future efforts to recognize and prevent DDD.

Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation.

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of ß-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.

Reduced bone mineral density in the first year after total pancreatectomy with islet autotransplantation (TPIAT).

BACKGROUND/OBJECTIVES: The effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. METHODS: We measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. RESULTS: In the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ -2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%-4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). CONCLUSIONS: TPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort.

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement. CONCLUSIONS: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.

Return to work after deceased donor kidney transplant under the kidney allocation system.

BACKGROUND: The Kidney Allocation System (KAS) includes a scoring system to match transplant candidate life expectancy with expected longevity of the donor kidney, and a backdating policy that gives waitlist time credit to patients waitlisted after starting dialysis treatment (post-dialysis). We estimated the effect of the KAS on employment among patient subgroups targeted by the policy. METHODS: We used a sample selection model to compare employment after transplant before and after KAS implementation among patients on the kidney-only transplant waitlist between December 4, 2011 and December 31, 2017. RESULTS: Post-dialysis transplant recipients aged 18-49 were significantly more likely to be employed 1-year post transplant in the post-KAS era compared to the pre-KAS era. Transplant recipients aged 35-64 with no dialysis treatment were significantly less likely to be employed 1 year after transplant in the post-KAS era compared to the pre-KAS era. CONCLUSIONS: This study provides the first assessment of employment after DDKT under the KAS and provides important information about both the methods used to measure employment after transplant and the outcome under the KAS. Changes in employment after DDKT among various patient subgroups have important implications for assessing long-term patient and societal effects of the KAS and organ allocation policy.

Performance of modified Igls criteria to evaluate islet autograft function after total pancreatectomy with islet autotransplantation - a retrospective study.

The Igls criteria assess islet function after islet allotransplant, based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia. However, these criteria as currently defined cannot be applied to total pancreatectomy islet autotransplant (TPIAT) patients. We tested modified criteria for assessing islet function in a large cohort of TPIAT patients (n = 379). Metabolic outcomes were assessed. We assigned Auto-Igls class to each patient as able and evaluated the utility, validity, and perioperative risk factors of Auto-Igls at 1-year post-IAT. We tested the association of Auto-Igls with independent measures of islet graft function, specifically continuous glucose monitoring (CGM) data or acute C-peptide response to glucose (ACRglu) from intravenous glucose tolerance tests. An Auto-Igls class was assigned to 264 patients (69%). Among patients who could not be classified, most were missing exact insulin dose. Seventy-three percent of TPIAT recipients were classified as optimal or good at 1 year. The only significant predictor of Auto-Igls class was islet mass transplanted (P < 0.0001). Auto-Igls class was associated with percent time in range (70-140 mg/dl) on CGM (P = 0.02) and ACRglu (P < 0.0001). Modified Igls classification for IAT permits simple, comprehensive assessment of metabolic outcomes after TPIAT and is associated with other islet functional measures.

Safe use of right lobe living donor livers with moderate steatosis in adult-to-adult living donor liver transplantation: a retrospective study.

Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.

Coronavirus disease 2019: Utilizing an ethical framework for rationing absolutely scarce health-care resources in transplant allocation decisions.

The novel coronavirus disease 2019 (COVID-19) is impacting transplant programs around the world, and, as the center of the pandemic shifts to the United States, we have to prepare to make decisions about which patients to transplant during times of constrained resources. In this paper, we discuss how to transition from the traditional justice versus utility consideration in organ allocation to a more nuanced allocation scheme based on ethical values that drive decisions in times of absolute scarcity. We recognize that many decisions are made based on the practical limitations that transplant programs face, especially at the extremes. As programs make the transition from a standard approach to a resource-constrained approach to transplantation, we utilize a framework for ethical decisions in settings of absolutely scarce resources to help guide programs in deciding which patients to transplant, which donors to accept, how to minimize risk, and how to ensure the best utilization of transplant team members.

Coronavirus disease 2019: Implications of emerging infections for transplantation.

The recent identification of an outbreak of 2019- novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.

Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD ≥40).

OBJECTIVE: To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. BACKGROUND: Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. METHODS: The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. RESULTS: We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. CONCLUSIONS: Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.

The histopathology of SPINK1-associated chronic pancreatitis.

BACKGROUND: The identification of genetic risk factors for chronic pancreatitis, such as PRSS1, CFTR and SPINK1, provides the opportunity to define key pathologic hallmarks and etiologic-specific changes. For example, pancreata from PRSS1 and CFTR patients exhibit progressive lipomatous atrophy without significant fibrosis. Considering the pathology of SPINK1-associated pancreatitis is ill-defined, we examined the pancreata of SPINK1 patients with chronic pancreatitis. METHODS: Histologic sections after total pancreatectomy with islet autotransplantation and associated clinicopathologic data were collected from 28 patients with SPINK1 germline alterations. Clinical findings, germline data, anatomic anomalies and pathologic findings were descriptively evaluated. RESULTS: Patients ranged in age from 5 to 48 years (median, 21.6 years) with abdominal pain between 2 and 25 years (median, 5.8 years). Most patients were SPINK1 heterozygous and 14 (50%) had co-occurring CFTR (n = 12) and CTRC (n = 2) mutations. Other pancreatitis risk factors included anatomic anomalies (n = 9) and tobacco use (n = 1). Overall, 24 (86%) patients had additional pancreatitis-associated germline alterations, SPINK1 homozygosity, anatomic anomalies or environmental factors. Examination of pancreata revealed a sequential pattern of exocrine parenchymal loss and replacement by prominent fibrosis, dependent on the duration of abdominal pain. No malignancies were identified, but low-grade pancreatic intraepithelial neoplasia was present for 2 cases. CONCLUSIONS: Within this descriptive study, SPINK1-associated pancreatitis is characterized by parenchymal fibrosis and suggests divergent pathophysiologic mechanisms from PRSS1 and CFTR-associated pancreatitis. Moreover, SPINK1 patients frequently had additional etiologic factors that did not impact the development of pancreatic fibrosis and may implicate SPINK1 as a disease modifier gene.