Estimating risk of prolonged mechanical ventilation after liver transplantation in children: PROVE-ALT score.

BACKGROUND: Children at high risk for prolonged mechanical ventilation (PMV) after liver transplantation (LT) need to be identified early to optimize pulmonary support, allocate resources, and improve surgical outcomes. We aimed to develop and validate a metric that can estimate risk for Prolonged Ventilation After LT (PROVE-ALT). METHODS: We identified preoperative risk factors for PMV by univariable analysis in a retrospective cohort of pediatric LT recipients between 2011 and 2017 (n = 205; derivation cohort). We created the PROVE-ALT score by mapping multivariable logistic regression coefficients as integers, with cutoff values using the Youden Index. We validated the score by C-statistic in a retrospectively collected separate cohort of pediatric LT recipients between 2018 and 2021 (n = 133, validation cohort). RESULTS: Among total 338 patients, 21% (n = 72) were infants; 49% (n = 167) had cirrhosis; 8% (n = 27) required continuous renal replacement therapy (CRRT); and 32% (n = 111) required management in hospital (MIH) before LT. Incidence of PMV post-LT was 20% (n = 69) and 3% (n = 12) required tracheostomy. Independent risk factors (OR [95% CI]) for PMV were cirrhosis (3.8 [1-14], p = .04); age <1-year (8.2 [2-30], p = .001); need for preoperative CRRT (6.3 [1.2-32], p = .02); and MIH before LT (12.4 [2.1-71], p = .004). PROVE-ALT score ≥8 [Range = 0-21] accurately predicted PMV in the validation cohort with 73% sensitivity and 80% specificity (AUC: 0.81; 95% CI: 0.71-0.91). CONCLUSION: PROVE-ALT can predict PMV after pediatric LT with a high degree of sensitivity and specificity. Once externally validated in other centers, PROVE-ALT will empower clinicians to plan patient-specific ventilation strategies, provide parental anticipatory guidance, and optimize hospital resources.

Trends in marginal lung allograft survival: Advanced-age donors improve.

INTRODUCTION: Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age >60 years, smoking history >20 pack-years, PaO2 /FiO2  < 300 mmHg, purulent bronchoscopic secretions, and chest radiograph infiltrates. METHODS: Our retrospective cohort study separated 27 803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras. RESULTS: Three definitions-low PaO2 /FiO2 , purulent bronchoscopic secretions, and abnormal chest radiographs-did not bear out as truly marginal, demonstrating lack of significantly elevated risk. Advanced donor age demonstrated considerable survival improvement (HR (95% CI): 1.47 (1.26-1.72) in 2005-2009 down to 1.14 (.97-1.35) for 2015-2019), with protective factors being recipients <60 years, moderate recipient BMI, and low Lung Allocation Score (LAS). Donors with smoking history failed to demonstrate any significant improvement (HR (95% CI): 1.09 (1.01-1.17) in 2005-2009 increasing to 1.22 (1.08-1.38) in 2015-2019). CONCLUSIONS: Advanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO2 /FiO2 , bronchoscopic secretions, and abnormal radiographs demonstrated survival on par with standard donors. Significant donor smoking history, a moderate risk factor, has failed to improve.

The use of tracheostomy to support critically ill children receiving orthotopic liver transplantation: a single-center experience.

BACKGROUND: Children with end-stage liver disease and multi-organ failure, previously considered as poor surgical candidates, can now benefit from liver transplantation (LT). They often need prolonged mechanical ventilation (MV) post-LT and may need tracheostomy to advance care. Data on tracheostomy after pediatric LT are lacking. METHOD: Retrospective chart review of children who required tracheostomy in the peri-LT period in a large, freestanding quaternary children's hospital from 2014 to 2019. RESULTS: Out of 205 total orthotopic LTs performed in 200 children, 18 (9%) required tracheostomy in the peri-transplant period: 4 (2%) pre-LT and 14 (7%) post-LT. Among those 14 needing tracheostomy post-LT, median age was 9 months [IQR = 7, 14] at LT and 10 months [9, 17] at tracheostomy. Nine (64%) were infants and 12 (85%) were cirrhotic at the time of LT. Seven (50%) were intubated before LT. Median MV days prior to LT was 23 [7, 36]. Eight (57%) patients received perioperative continuous renal replacement therapy (CRRT). The median MV days from LT to tracheostomy was 46 [33, 56]; total MV days from initial intubation to tracheostomy was 57 [37, 66]. Four (28%) children died, of which 3 (21%) died within 1 year of transplant. Total ICU and hospital length of stay were 92 days [I72, 126] and 177 days [115, 212] respectively. Among survivors, 3/10 (30%) required MV at home and 8/10 (80%) were successfully decannulated at 400 median days [283, 584]. CONCLUSION: Tracheostomy though rare after LT remains a feasible option to support and rehabilitate critically ill children who need prolonged MV in the peri-LT period.

The impact of diabetes on young transplant recipients: An American perspective.

Despite advancements in diabetic care, diabetic kidney transplant recipients have significantly worse outcomes than non-diabetics. AIM: Our study aims to demonstrate the impact of diabetes, types I and II, on American young adults (18-40 years old) requiring kidney transplantation. METHODS: Using the United Network for Organ Sharing database, we conducted a population cohort study that included all first-time, kidney-only transplant recipients during 2002-2019, ages 18-40 years old. Patients were grouped according to indication for transplant. Primary outcomes were cumulative all-cause mortality and death-censored graft failure. Death-censored graft failure and patient survival at 1, 5, and 10 years were calculated via the Kaplan-Meier method. Multivariate Cox regression was used to assess for potential confounders. RESULTS: Of 42 466 transplant recipients, 3418 (8.1%) had end-stage kidney disease associated with diabetes. At each time-point, cumulative mortality was higher in diabetics compared to patients with non-diabetic causes of renal failure. Conversely, cumulative graft failure was similar between the groups. Adjusted hazard ratios for all-cause mortality and graft failure in diabetics were 2.99 (95% CI 2.67-3.35; p < .01) and 0.98 (95% CI 0.92-1.05, p < .01), respectively. CONCLUSION: Diabetes mellitus in young adult kidney transplant recipients is associated with a nearly three-fold increase in mortality, reflecting a relatively vulnerable patient population. Identifying the underlying causes of poor outcomes in this population should be a priority for future study.

Consistent improvements in short- and long-term survival following heart transplantation over the past three decades.

BACKGROUND: Despite noted improvements in short-term survival outcomes following orthotopic heart transplantation (OHT), review of the relevant literature suggests little improvement in long-term outcomes for patients surviving beyond 1 year. METHODS: All OHT cases performed between 1989 and 2019 within the United Network for Organ Sharing (UNOS) database were reviewed. Adults who underwent isolated OHT were included in a 1-year survival analysis. Those who survived at least 1 year post-transplant were included in a long-term survival analysis. Demographic factors were assessed using Students' t test and chi-square analysis. Survival trends and risk factors were assessed using the Kaplan-Meier and the Cox regression analysis, respectively. RESULTS: A total of 53 265 and 46 372 recipients were included in the short-term and long-term cohorts, respectively. In an adjusted analysis, the reference implant era 2014-2019 had significantly better short-term survival outcomes when compared with earlier implant eras: 1989-1993 (HR: 2.92), 1994-1998 (HR: 1.53), 1999-2003 (HR: 1.27), 2004-2008 (HR: 1.11), and 2009-2013 (HR: 1.02). The same trend was recognized for long-term outcomes: 1989-1993 (HR: 1.87), 1994-1998 (HR: 1.27), 1999-2003 (HR: 1.09), and 2004-2008 (HR: 1.03). CONCLUSIONS: Despite increases in multiple traditional risk factors, both short-term and long-term survival outcomes have consistently improved over the past 30 years, suggesting other factors are contributing to improved outcomes in recent eras.

Allograft discard risk index for heart transplantation.

BACKGROUND: The numberof patients awaiting heart transplantation (HTx) substantially exceeds the number of donor hearts transplanted each year, yet nearly 65% of eligible donor hearts are discarded rather than transplanted. METHODS: Deceased organ donors listed within the UNOS Deceased Donor Database between 2010 and 2020 were reviewed. Those greater than 10 years old and consented for heart donation were included and randomly separated into training (n = 48 435) and validation (n = 24 217) cohorts. A discard risk index (DSRI) was created using the results of univariable and multivariable analyses. Discard data were assessed at DSRI value deciles, and stratum-specific likelihood ratio (SSLR) analysis and Kaplan-Meier survival function were used for mortality data. RESULTS: Factors associated with higher DSRI values included donor age > 45, LVEF, HBV-core antibodies, hypertension, and diabetes. The DSRI C-statistic was .906 in the training cohort and .904 in the validation cohort. The DSRI did not reliably predict 30-day or 1-year mortality after transplantation (C-statistic .539 and .532, respectively). CONCLUSIONS: The factors leading to heart allograft discard are not correlated to the same degree with post-transplant outcomes. This suggests that optimizing utilization of certain allografts with slightly higher risk of discard could increase the heart donor pool with limited impact on posttransplant mortality.

Impact of the Treating Hospital on Care Outcomes for Hepatocellular Carcinoma.

Multidisciplinary hepatocellular carcinoma (HCC) treatment is associated with optimal outcomes. There are few data analyzing the impact of treating hospitals' therapeutic offerings on survival. We performed a retrospective cohort study of patients aged 18-70 years with HCC in the National Cancer Database (2004-2012). Hospitals were categorized based on the level of treatment offered (Type I-nonsurgical; Type II-ablation; Type III-resection; Type IV-transplant). Associations between overall risk of death and hospital type were evaluated with multivariable Cox shared frailty modeling. Among 50,381 patients, 65% received care in Type IV hospitals, 26% in Type III, 3% in Type II, and 6% in Type I. Overall 5-year survival across modalities was highest at Type IV hospitals (untreated: Type IV-13.1% versus Type I-5.7%, Type II-7.0%, Type III-7.4% [log-rank, P < 0.001]; chemotherapy and/or radiation: Type IV-18.1% versus Type I-3.6%, Type II-4.6%, Type III-7.7% [log-rank, P < 0.001]; ablation: Type IV-33.3% versus Type II-13.6%, Type III-23.6% [log-rank, P < 0.001]; resection: Type IV-48.4% versus Type III-39.1% [log-rank, P < 0.001]). Risk of death demonstrated a dose-response relationship with the hospital type-Type I (ref); Type II (hazard ratio [HR] 0.81, 95% confidence interval [0.73-0.90]); Type III (HR 0.67 [0.62-0.72]); Type IV hospitals (HR 0.43 [0.39-0.47]). Conclusion: Although care at hospitals offering the full complement of HCC treatments is associated with decreased risk of death, one third of patients are not treated at these hospitals. These data can inform the value of health policy initiatives regarding regionalization of HCC care.

Standing the test of time: outcomes of a decade of prioritizing patients with hepatocellular carcinoma, results of the UNOS natural geographic experiment.

UNLABELLED: Priority is given to patients with hepatocellular carcinoma (HCC) to receive liver transplants, potentially causing significant regional disparities in organ access and possibly outcomes in this population. Our aim was to assess these disparities by comparing outcomes in long waiting time regions (LWTR, regions 5 and 9) and short waiting time regions (SWTR regions 3 and 10) by analyzing the United Network for Organ Sharing (UNOS) database. We analyzed 6,160 HCC patients who received exception points in regions 3, 5, 9, and 10 from 2002 to 2012. Data from regions 5 and 9 were combined and compared to data from regions 3 and 10. Survival was studied in three patient cohorts: an intent-to-treat cohort, a posttransplant cohort, and a cohort examining overall survival in transplanted patients only (survival from listing to last posttransplant follow-up). Multivariate analysis and log-rank testing were used to analyze the data. Median time on the list in the LWTR was 7.6 months compared to 1.6 months for SWTR, with a significantly higher incidence of death on the waiting list in LWTR than in SWTR (8.4% versus 1.6%, P < 0.0001). Patients in the LWTR were more likely to receive loco-regional therapy, to have T3 tumors at listing, and to receive expanded-criteria donor (ECD) or donation after cardiac death (DCD) grafts than patients in the SWTR (P < 0.0001 for all). Survival was significantly better in the LWTR compared to the SWTR in all three cohorts (P < 0.0001 for all three survival points). Being listed/transplanted in an SWTR was an independent predictor of poor patient survival on multivariate analysis (P < 0.0001, hazard ratio = 1.545, 95% confidence interval 1.375-1.736). CONCLUSION: This study provides evidence that expediting patients with HCC to transplant at too fast a rate may adversely affect patient outcomes.

Retrospective Analysis of the Impact of High- and Low-Quality Donor Livers for Patients with High-Acuity Illness.

BACKGROUND Patients with high-acuity liver failure have increased access to marginal and split liver options, owing to historically high waitlist mortality rates. While most research states that donor liver quality has no impact on patients with high-acuity illness, there have been inconsistencies in recent research on how liver quality impacts post-transplant outcomes for these patients. We aimed to quantify donor liver quality with various post-transplantation patient outcomes for patients with high-acuity illness. MATERIAL AND METHODS Using the liver donor risk index (LDRI), model for end stage liver disease (MELD), and clinically relevant recipient factors, we used multivariate logistic regression to analyze how donor liver quality affects varying measures of patient outcomes for 9923 high-acuity patients from June 18, 2013, to June 18, 2022. RESULTS Using LDRI, high-quality livers had a significant protective impact on high-acuity patient mortality, compared with low-quality livers (OR=0.695 [0.549, 0.879], P=0.002). High-quality livers also had significant impact on graft survival (OR=0.706 [0.558, 0.894], P=0.004). Two sensitivity patient mortality analyses, excluding patients with status 1A and hepatocellular carcinoma, showed significant protective findings for high-quality livers. High-quality livers had insignificant outcomes on long-term survivor mortality, length of hospitalization, and primary non-function outcomes, compared with low-quality donor livers. CONCLUSIONS While our findings suggest donor quality has an impact on high-acuity patient outcomes, these findings indicate further research is needed in intent-to-treat analysis on clinical offer data to provide a clearer finding of how donor quality affects patients with high-acuity illness.

A Surgical Collaborative to Empower Medical Student Research.

Mini abstracts: Faculty at the Baylor College of Medicine have developed a flexible research collaborative through which students gain research skills and individualized mentorship. This division has produced 86 trainee first author publications, 64 manuscripts by 34 different medical students with an average Scimago Journal Rank of 1.293 (range: 1.035-1.551) since 2015.

HLA mismatch is important for 20-year graft survival in kidney transplant patients.

BACKGROUND: Human leukocyte antigens (HLA) matching is gradually being omitted from clinical practice in evaluation for renal allograft transplant. While such practices may yield shorter wait times and adequate short-term outcomes, graft longevity in HLA mismatched patients remains unclear. This study aims to demonstrate that HLA matching may still play an important role in long-term graft survival. METHODS: We identified patients undergoing an index kidney transplant in the United Network for Organ Sharing (UNOS) data from 1990 to 1999, with one-year graft survival. The primary outcome of the analysis was graft survival beyond 10 years. We explored the long-lasting impact of HLA mismatches by landmarking the analysis at established time points. RESULTS: We identified 76,530 patients receiving renal transplants in the time frame, 23,914 from living donors and 52,616 from deceased donors. On multivariate analysis, more HLA mismatches were associated with worse graft survival beyond 10 years for both living and deceased donor allografts. HLA mismatch continued to remain an essential factor in the long term. CONCLUSIONS: A greater number of HLA mismatches was associated with progressively worse long-term graft survival for patients. Our analysis reinforces the importance of HLA matching in the preoperative evaluation of renal allografts.

Allograft discard risk index for lung transplantation.

BACKGROUND: The demand for donor lungs continues to outpace the supply, yet nearly 75% of donor lungs intended for lung transplantation are discarded. METHODS: We reviewed all donation after brain death organ donors listed within the UNOS Deceased Donor Database between 2005 and 2020. Univariable and multivariable analyses were run on the training set (n = 69,355) with the primary outcome defined as lung discard, and the results were used to create a discard risk index (DSRI). Discard data were assessed at DSRI value deciles using the validation set (n = 34,670), and differences in 1-year mortality were assessed using stratum-specific likelihood ratio (SSLR) analysis. RESULTS: Donor factors most associated with higher DSRI values included age > 65, PaO2 < 300, hepatitis C virus, and cigarette use. Factors associated with lower DSRI values included donor age < 40 and PaO2 > 400. The DSRI was a reliable predictor of donor discard, with a C-statistic of 0.867 in the training set and 0.871 in the validation set. The DSRI was not a reliable predictor of 30-day, 1-year, 3-year, and 5-year survival following transplantation (C-statistic 0.519-0.530). SSLR analysis resulted in three 1-year mortality strata (SSLR 0.88 in the 1st DSRI value decile, 1.03 in the 2nd-5th, & 1.19 in the 6th-10th). CONCLUSIONS: The factors leading to lung allograft discard are not the same as those leading to worse recipient outcomes. This suggests that with proper allocation, many of the grafts that are now commonly discarded could be used in the future donor pool with limited impact on mortality.

Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma.

BACKGROUND: The Milan criteria have been adopted by United Network for Organ Sharing (UNOS) to preoperatively assess outcome in patients with hepatocellular carcinoma (HCC) who receive orthotopic liver transplantation (OLT). These criteria rely solely on radiographic appearances of the tumor, providing no measure of tumor biology. Recurrence rates, therefore, remain around 20% for patients within the criteria. The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status previously established as a prognostic indicator in colorectal liver metastases. We aimed to determine whether NLR predicts outcome in patients undergoing OLT for HCC. DESIGN: Analysis of patients undergoing OLT for HCC between 2001 and 2007 at our institution. A NLR > or =5 was considered to be elevated. RESULTS: : A total of 150 patients were identified, with 13 patients having an elevated NLR. Of these, 62% developed recurrence compared with 14% with normal NLR (P < 0.0001). The disease-free survival for patients with high NLR was significantly worse than that for patients with normal NLR (1-, 3-, and 5-year survivals of 38%, 25%, and 25% vs. 92%, 85%, and 75%, P < 0.0001). Patients with high NLR also had poorer overall survival (5-year survival, 28% vs. 64%, P = 0.001). Patients within Milan with an elevated NLR had significantly poorer disease-free survival than those with normal NLR within Milan (5-year survival, 30% vs. 81%, P < 0.0001). On univariate analysis, 9 factors including an NLR > or =5 were significant predictors of poor disease-free survival. However, only a raised NLR remained significant on multivariate analysis (P = 0.005, HR: 19.98). CONCLUSION: Elevated NLR significantly increases the risk for tumor recurrence and recipient death. Preoperative NLR measurement may provide a simple method of identifying patients with poorer prognosis and act as an adjunct to Milan in determining, which patients benefit most from OLT.

A case of portal venous gas after extracorporeal shockwave lithotripsy and obstructive pyelonephritis.

The presence of gas in the portal venous system is considered an ominous sign often mandating immediate exploratory laparotomy; however, there are numerous reports of benign incidences of this finding. This report describes a case of portal venous gas after extracorporeal shockwave lithotripsy. The patient had the rare complication of obstructive pyleonephritis that progressed to sepsis and subsequently underwent a negative exploratory laparotomy. It is suggested that the radiographic finding of portal venous gas should be correlated with the likely cause and overall clinical picture.