Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy.

BACKGROUND AND AIMS: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group. APPROACH AND RESULTS: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n  = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 µmol/L ( n  = 43) or >40 µmol/L ( n  = 94) groups. At 2 years of age, the ≤40 µmol/L compared with >40 µmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person-years of follow-up, those in the ≤40 µmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 µmol/L group had a 10-year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%-26.1%), compared with 42.9% (95% CI: 28.6%-56.4%) for the >40 µmol/L group ( p  = 0.001). CONCLUSIONS: Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS. CONCLUSIONS: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important.

Living Donor Decision-Making and the Complex Interplay of Finances and Other Motivators, Barriers, and Facilitators.

INTRODUCTION: The decision to become a living donor requires consideration of a complex, interactive array of factors that could be targeted for clinical, policy, and educational interventions. Our objective was to assess how financial barriers interact with motivators, other barriers, and facilitators during this process. METHODS: Data were obtained from a public survey assessing motivators, barriers, and facilitators of living donation. We used multivariable logistic regression and consensus k-means clustering to assess interactions between financial concerns and other considerations in the decision-making process. RESULTS: Among 1592 respondents, the average age was 43; 74% were female and 14% and 6% identified as Hispanic and Black, respectively. Among employed respondents (72%), 40% indicated that they would not be able to donate without lost wage reimbursement. Stronger agreement with worries about expenses and dependent care challenges was associated with not being able to donate without lost wage reimbursement (OR = 1.2, 95% CI = 1.0-1.3; OR = 1.2, 95% CI = 1.1-1.3, respectively). Four respondent clusters were identified. Cluster 1 had strong motivators and facilitators with minimal barriers. Cluster 2 had barriers related to health concerns, nervousness, and dependent care. Clusters 3 and 4 had financial barriers. Cluster 3 also had anxiety related to surgery and dependent care. CONCLUSIONS: Financial barriers interact primarily with health and dependent care concerns when considering living organ donation. Targeted interventions to reduce financial barriers and improve provider communication regarding donation-related risks are needed.

Comparing clinical bladder diaries and recalled patient reports for measuring lower urinary tract symptoms in the symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Bladder diaries are a key source of information about lower urinary tract symptoms (LUTS); however, many patients do not complete them as instructed. Questionnaire-based patient-reported outcome measures (PROMs) are another option for reporting LUTS but may have recall bias. We assessed the strength of the associations between PROMs and a 3-day bladder diary. MATERIALS AND METHODS: Symptomatic adults from 6 tertiary care sites completed a 3-day paper bladder diary and 3-, 7-, and 30-day electronic PROMs. We assessed the linear associations between mapped pairs of diary variables and responses to PROM items using biserial and polyserial correlation coefficients with 95% confidence intervals. RESULTS: Of 290 enrolled participants, 175 (60%) completed the bladder diary as instructed and at least one corresponding PROM. Linear associations were strongest between the diary and 3-day recall of daytime frequency (r = 0.75) and nighttime frequency (r = 0.69), followed by voids with urgency sensations (r = 0.62), and an item reporting any incontinence (r = 0.56). Linear associations between bladder diary and specific incontinence variables (e.g., stress, urgency) were low to negligible (ranging from r = 0.16-0.39). Linear associations were consistent across the 3-, 7-, and 30-day recall periods. CONCLUSIONS: Missing and unusable bladder diary data were common, highlighting the patient burden associated with this method of data collection. A questionnaire-based PROM is a reasonable alternative to a diary for reporting voiding frequency and may offer an easier option for reporting some symptoms.

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors.

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow-up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs' NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.

Satisfaction with life and depressive symptoms in living organ donors and non-donors: New insights from the National Living Donor Assistance Center.

BACKGROUND: Previous studies indicate there may be psychological consequences of being unable to serve as a living donor, but these have not been explored in a large national cohort of low-income individuals who initiated living donor evaluation in US transplant centers. METHODS: Using data from 6574 National Living Donor Assistance Center (NLDAC) participants (November 1, 2007-December 31, 2018), we utilized a cross-sectional study design to evaluate short-term depressive symptoms and satisfaction with life in living donors and non-donors (those who were declined or withdrew from evaluation) using the Satisfaction with Life Scale (SWLS) and the PHQ-8, with and without risk adjustment using linear regression. RESULTS: National Living Donor Assistance Center participants originated from 207 US transplant centers. 52% of NLDAC participants responded to the survey (n = 3423; donors = 2848 (58.6% of all donors), non-donors = 575 (33.5% of all non-donors); ncenters  = 201)). Respondents were significantly older, more likely to be female, white, non-Hispanic, married, more educated, more full-time employed, and more likely to be unrelated to the recipient vs non-respondents (all, P < .001). Among survey respondents, donors were significantly younger, more likely to be non-Hispanic, employed, and related to the recipient compared to non-donors (all, P < .05). Higher PHQ-8 scores were correlated with lower SWL scores (r = -.32, P < .001). Both groups displayed high SWLS (donors vs non-donors: 27.1 vs 26.3, P = .002). Both groups had low levels of depressive symptoms overall, but donors had more symptoms than non-donors (3.5 vs 2.4, P < .001). After risk adjustment, non-donors had significantly less depressive symptoms by PHQ-8 (28% lower, P < .001), but had lower life satisfaction (1.2 points lower, P < .001). CONCLUSIONS: Donors and non-donors have high global levels of overall life satisfaction and low levels of depressive symptoms at 8 weeks after donation or denial. While small effect sizes were observed between groups in these outcomes, being a non-donor was an independent risk factor for lower life satisfaction, which warrants further evaluation.

Symptom Based Clustering of Men in the LURN Observational Cohort Study.

PURPOSE: Conventional classification of patients with lower urinary tract symptoms into diagnostic categories based on a predefined symptom complex or predominant symptom appears inadequate. This is due to the frequent presentation of patients with multiple urinary symptoms which could not be perfectly categorized into traditional diagnostic groups. We used a novel clustering method to identify subtypes of male patients with lower urinary tract symptoms based on detailed multisymptom information. MATERIALS AND METHODS: We analyzed baseline data on 503 care seeking men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms and symptom severity were assessed using the LUTS (Lower Urinary Tract Symptoms) Tool and the AUA SI (American Urological Association Symptom Index), which include a total of 52 questions. We used a resampling based consensus clustering algorithm to identify patient subtypes with distinct symptom signatures. RESULTS: Four distinct symptom clusters were identified. The 166 patients in cluster M1 had predominant symptoms of frequency, nocturia, hesitancy, straining, weak stream, intermittency and incomplete bladder emptying suggestive of bladder outlet obstruction. The 93 patients in cluster M2 mainly endorsed post-micturition symptoms (eg post-void dribbling and post-void leakage) with some weak stream. The 114 patients in cluster M3 reported mostly urinary frequency without incontinence. The 130 patients in cluster M4 reported severe frequency, urgency and urgency incontinence. Most other urinary symptoms statistically differed between cluster pairs. Patient reported outcomes of bowel symptoms, mental health, sleep dysfunction, erectile function and urological pain significantly differed across the clusters. CONCLUSIONS: We identified 4 data derived clusters among men seeking care for lower urinary tract symptoms. The clusters differed from traditional diagnostic categories. Further subtype refinement will be done to incorporate clinical data and nonurinary patient reported outcomes.

Are three-day voiding diaries feasible and reliable? Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) cohort.

AIMS: The aims of this study were to assess the completeness of voiding diaries in a research context and to correlate diary data with patient-reported questionnaires. METHODS: Men and women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were given a 3-day voiding and fluid-intake diary to fill-out. Diaries were assessed for completeness and intake-output imbalances. They were assigned to one of four categories based on a percentage of missing data and fluid imbalance: no diary submitted, unusable (>40% missing void or intake volumes, or unphysiological fluid imbalance), usable but not complete, and complete. RESULTS: A total of 1064 participants were enrolled and 85% (n = 902) returned the bladder diary. Of the diaries returned, 94% (n = 845) had data on three separate days, 87% (n = 786) had no missing intake volumes, 61% (n = 547) had no missing voided volumes, and 70% (n = 635) had a fluid imbalance within 3 L across the 3-day time period, resulting in 50% (n = 448) of participants with 100% complete diaries. Younger age was associated with a higher likelihood of not submitting a diary, or submitting an unusable diary. Women had a higher likelihood of submitting an unusable diary or a usable but incomplete diary. CONCLUSION: Overall, 50% of LURN participants returned voiding diaries with perfectly complete data. Incomplete data for voided volumes was the most common deficiency. There was only a moderate correlation between diary data and questionnaire responses, indicating that diaries are a source of unique information.

Life and expectations post-kidney transplant: a qualitative analysis of patient responses.

BACKGROUND: The effect of a kidney transplant on a recipient extends beyond the restoration of kidney function. However, there is limited qualitative analysis of recipient perspectives on life following transplantation, particularly in the United States. To understand the full patient experience, it is necessary to understand recipient views on life adjustments after kidney transplantation, medical management, and quality of life. This could lead to improvements in recipient care and sense of well-being. METHODS: We conducted a paper-based survey from March 23 to October 1, 2015 of 476 kidney transplant recipients at the University of Michigan Health System in Ann Arbor, Michigan. We analyzed their open-ended responses using qualitative research methods. This is a companion analysis to a previous quantitative report on the closed-ended responses to that survey. RESULTS: Common themes relating to changes following transplantation included: improvements in quality of life, a return to normalcy, better health and more energy. Concerns included: duration of graft survival, fears about one day returning to dialysis or needing to undergo another kidney transplant, comorbidities, future quality of life, and the cost and quality of their healthcare. Many recipients were grateful for their transplant, but some were anxious about the burdens transplantation placed on their loved ones. CONCLUSIONS: While most recipients reported meaningful improvements in health and lifestyle after kidney transplantation, a minority of participants experienced declines in energy or health status. Worries about how long the transplant will function, future health, and cost and quality of healthcare are prevalent. Future research could study the effects of providing additional information, programs, and interventions following transplantation that target these concerns. This may better prepare and support kidney recipients and lead to improvements in the patient experience.

Kidney transplant graft outcomes in 379 257 recipients on 3 continents.

Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow-up registry data from 1988-2014 for 379 257 recipients of first kidney-only transplants using Cox regression. Compared to the United States, 1-year adjusted graft failure risk was significantly higher in the United Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18-1.26, P < .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14-1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84-0.96, P = .001). In contrast, long-term adjusted graft failure risk (conditional on 1-year function) was significantly higher in the United States compared to Australia, New Zealand, and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001). Thus long-term kidney graft outcomes are approximately 25% worse in the United States than in 3 other countries with well-developed kidney transplant systems. Case mix differences and residual confounding from unmeasured factors were found to be unlikely explanations. These findings suggest that identification of potentially modifiable country-specific differences in care delivery and/or practice patterns should be sought.

Mental Health, Sleep and Physical Function in Treatment Seeking Women with Urinary Incontinence.

PURPOSE: We examined how mental health measures, sleep and physical function are associated with the presence and type of urinary incontinence and severity in women seeking treatment for lower urinary tract symptoms. MATERIALS AND METHODS: This baseline cross-sectional analysis was performed in treatment seeking women with lower urinary tract symptoms. All participants completed the LUTS (Lower Urinary Tract Symptoms) Tool (Pfizer, New York, New York), which was used to classify women based on urinary incontinence symptoms and measure severity. The PROMIS (Patient-Reported Outcomes Measurement Information System) questionnaire for depression, anxiety, sleep disturbance and physical function, the PSS (Perceived Stress Scale) and the IPAQ-SF (International Physical Activity Questionnaire Short Form) were administered. Multivariable regression modeling was done to assess associations with urinary symptom presence, type and severity. RESULTS: We studied 510 women with a mean ± SD age of 56 ± 14 years. Of the women 82% were Caucasian, 47% were obese and 14% reported diabetes. Urinary incontinence was reported by 420 women (82.4%), including stress urinary incontinence in 70, urgency urinary incontinence in 85, mixed urinary incontinence in 240 and other urinary incontinence in 25. On adjusted analyses there was no difference in any mental health, sleep or physical function measure based on the presence vs the absence of urinary incontinence. Among women with urinary incontinence PROMIS anxiety and sleep disturbance scores were higher in those with mixed urinary incontinence than stress urinary incontinence. Increasing urinary incontinence severity was associated with higher PROMIS depression and anxiety scores, and higher PSS scores. However, higher urinary incontinence severity was not associated with a difference in sleep or physical function. CONCLUSIONS: Among treatment seeking women with lower urinary tract symptoms, increasing urinary incontinence severity rather than the presence or type of urinary incontinence was associated with increased depression, anxiety and stress.

Symptom Based Clustering of Women in the LURN Observational Cohort Study.

PURPOSE: Women with lower urinary tract symptoms are often diagnosed based on a predefined symptom complex or a predominant symptom. There are many limitations to this paradigm as often patients present with multiple urinary symptoms which do not perfectly fit the preestablished diagnoses. We used cluster analysis to identify novel, symptom based subtypes of women with lower urinary tract symptoms. MATERIALS AND METHODS: We analyzed baseline urinary symptom questionnaire data obtained from 545 care seeking female participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Observational Cohort Study. Symptoms were measured with the LUTS (lower urinary tract symptoms) Tool and the AUA SI (American Urological Association Symptom Index), and analyzed using a probability based consensus clustering algorithm. RESULTS: Four clusters were identified. The 138 women in cluster F1 did not report incontinence but experienced post-void dribbling, frequency and voiding symptoms. The 80 women in cluster F2 reported urgency incontinence as well as urgency and frequency but minimal voiding symptoms or stress incontinence. Cluster F3 included 244 women who reported all types of incontinence, urgency, frequency and mild voiding symptoms. The 83 women in cluster F4 reported all lower urinary tract symptoms at uniformly high levels. All but 2 of 44 LUTS Tool and 8 AUA SI questions significantly differed between at least 2 clusters (p <0.05). All clusters contained at least 1 member from each conventional group, including continence, and stress, urgency, mixed and other incontinence. CONCLUSIONS: Women seeking care for lower urinary tract symptoms cluster into 4 distinct symptom groups which differ from conventional clinical diagnostic groups. Further validation is needed to determine whether management improves using this new classification.

Reasons for Seeking Clinical Care for Lower Urinary Tract Symptoms: A Mixed Methods Study.

PURPOSE: The primary objective of this study was to evaluate reasons for seeking care among men and women with lower urinary tract symptoms. MATERIALS AND METHODS: Participants were recruited from urology and urogynecology clinics, and the community. The sample was enriched with persons expected to have abnormal or diminished bladder sensations (eg participants with lower back surgery and participants 65 years old or older). Interviews were performed in person beginning with an open-ended assessment of urinary symptoms and associated bother followed by more directed questions, including reasons for seeking or not seeking treatment. We also examined the relationship between symptom frequency and bother using the LUTS (Lower Urinary Tract Symptoms) Tool. RESULTS: A total of 88 participants, including 38 men and 50 women, with a mean ± SD age of 52.2 ± 14.3 years provided information about urinary symptoms, including a range of quality of life consequences and coping behaviors. They sought treatment mostly because of new, continuing or bothersome symptoms. Factors associated with not seeking treatment included low symptom severity and concerns about the costs vs the benefits of treatment (eg side effects of medication). Symptom frequency and bother were associated with each other across symptoms assessed by the LUTS Tool. CONCLUSIONS: In this large qualitative study we obtained useful insights into the impact of lower urinary tract symptoms from the perspective of the person with the symptoms. Removing barriers and misconceptions about the treatment of lower urinary tract symptoms may increase the number of people who seek clinical care and improve the clinical course of men and women who experience lower urinary tract symptoms.

Estimating the effect of a rare time-dependent treatment on the recurrent event rate.

In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized.

Return on investment for financial assistance for living kidney donors in the United States.

BACKGROUND: The National Living Donor Assistance Center (NLDAC) enables living donor kidney transplants through financial assistance of living donors, but its return on investment (ROI) through savings on dialysis costs remains unknown. METHODS: We retrospectively reviewed 2012-2015 data from NLDAC, the United States Renal Data System, and the Scientific Registry of Transplant Recipients to construct 1-, 3-, and 5-year ROI models based on NLDAC applications and national dialysis and transplant cost data. ROI was defined as state-specific federal dialysis cost minus (NLDAC program costs plus state-specific transplant cost), adjusted for median waiting time (WT). RESULTS: A total of 2425 NLDAC applications were approved, and NLDAC costs were USD $6.76 million. Median donor age was 41 years, 66.1% were female, and median income was $33 759; 43.6% were evaluated at centers with WT >72 months. Median dialysis cost/patient-year was $81 485 (IQR $74 489-$89 802). Median kidney transplant cost/patient-year was $30 101 (IQR $26 832-$33 916). Overall, ROI varied from 5.1-fold (1-year) to 28.2-fold (5-year), resulting in $256 million in savings. Higher ROI was significantly associated with high WT, larger dialysis and transplant costs differences, and more NLDAC applicants completing the donation process. CONCLUSIONS: Financial support for donor out-of-pocket expenses produces dramatic federal savings through incremental living donor kidney transplants.

Bowel function, sexual function, and symptoms of pelvic organ prolapse in women with and without urinary incontinence.

AIMS: Bowel symptoms, pelvic organ prolapse, and sexual dysfunction are common, but their frequency among women with lower urinary tract symptoms (LUTS) has not been well described. Our aims were to describe pelvic floor symptoms among women with and without urinary incontinence (UI) and among subtypes of UI. METHODS: Women with LUTS seeking care at six U.S. tertiary care centers enrolled in prospective cohort study were studied. At baseline, participants completed the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Organ Prolapse/Incontinence Sexual Questionnaire (PISQ-IR), and PROMIS GI Diarrhea, Constipation, and Fecal Incontinence Scales. RESULTS: Mean age among the 510 women was 56.4 ± 14.4 years. Women who reported UI (n = 420) had more diarrhea and constipation symptoms (mean scores 49.5 vs 46.2 [P = 0.01] and 51.9 vs 48.4 [P < 0.01], respectively) at baseline. Among sexually active women, mean PISQ-IR subscale scores were lower among those with UI (condition specific: 89.8 vs 96.7, P < 0.01; condition impact: 79.8 vs 92.5, P < 0.01). Women with mixed urinary incontinence (MUI) (n = 240) reported more prolapse symptoms, fecal incontinence, and worse sexual function compared to those with stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). CONCLUSIONS: Women presenting with LUTS with UI reported significantly worse constipation, diarrhea, fecal incontinence, and sexual function compared to women without UI. In women with UI, sexual function and pelvic organ prolapse (POP) symptoms were worse in those with MUI compared to SUI and UUI.

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients.

BACKGROUND & AIMS: Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors. METHODS: We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors. RESULTS: At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes. CONCLUSIONS: Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.

National assessment of early hospitalization after liver transplantation: Risk factors and association with patient survival.

Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for "early" hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post-LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient-year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate-adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow-up months 0-6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143-1152 2017 AASLD.

Biliary reconstructive techniques and associated anatomic variants in adult living donor liver transplantations: The adult-to-adult living donor liver transplantation cohort study experience.

Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD.

Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review.

PURPOSE: Diet, fluid intake and caffeine, alcohol and tobacco use may have effects on lower urinary tract symptoms. Constructive changes in these modifiable nonurological factors are suggested to improve lower urinary tract symptoms. To better understand the relationship between nonurological factors and lower urinary tract symptoms, we performed a systematic literature review to examine, grade and summarize reported associations between lower urinary tract symptoms and diet, fluid intake and caffeine, tobacco and alcohol use. MATERIALS AND METHODS: We performed PubMed® searches for eligible articles providing evidence on associations between 1 or more nonurological factors and lower urinary tract symptoms. A modified Oxford scale was used to grade the evidence. RESULTS: We reviewed 111 articles addressing diet (28 studies), fluid intake (21) and caffeine (21), alcohol (26) and tobacco use (44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3 and 59% level 4). Fluid intake and caffeine use were associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with decreased likelihood of benign prostatic hyperplasia diagnosis and reduced lower urinary tract symptoms in men. Associations between lower urinary tract symptoms and ingestion of certain foods and tobacco were inconsistent. CONCLUSIONS: Evidence of associations between lower urinary tract symptoms and diet, fluid intake and caffeine, alcohol and tobacco use is sparse and mostly observational. However, there is evidence of associations between increased fluid and caffeine intake and urinary frequency/urgency, and between modest alcohol intake and decreased benign prostatic hyperplasia diagnosis and lower urinary tract symptoms. Given the importance of these nonurological factors in daily life, and their perceived impact on lower urinary tract symptoms, higher quality evidence is needed.