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 large 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 vs deceased donors. Results At least 1 BPAR episode occurred in 239/890 recipients in A2ALL (26.9%) and 7066/45,423 recipients in SRTR (15.6%). In each study, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% CI, 0.43–0.76 and SRTR HR, 0.78; 95% CI, 0.66–0.91) (P<.001) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each study, 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. The 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). The 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. LDLT from a biologically related donor is associated with decreased risk of rejection.

Objective To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers to outcomes of deceased donor liver transplant (DDLT) and identify key variables impacting patient and graft survival. Summary Background Data The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) is a prospective multicenter NIH study comparing outcomes of LDLT and DDLT and associated risks. Methods Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in A2ALL transplanted between 1/1/1998 and 1/31/2014 at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. Results Survival probability at 10 years was 70% for LDLT and 64% for DDLT. Unadjusted survival was higher with LDLT (HR=0.76, p=0.02) but attenuated after adjustment (HR=0.98, p=0.90) as LDLT recipients had lower mean MELD (15.5 vs 20.4) and fewer were transplanted from ICU, inpatient, on dialysis, ventilated, or with ascites. Post-transplant ICU days were less for LDLT. For all recipients female gender and primary sclerosing cholangitis were associated with improved survival, while dialysis and older recipient/donor age were associated with worse survival. Higher MELD score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. Conclusions LDLT provides significant long-term transplant benefit resulting in transplantation at a lower MELD score, decreased death on waitlist, and excellent post-transplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision-making regarding timing of transplant and donor options. Clinical Trials ID NCT00096733.

Purpose To describe and compare the frequency and type of lower urinary tract symptoms (LUTS) reported by men and women at the time they were recruited from urology and urogynecology clinics into the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) multi-center, prospective, observational cohort study. Materials and Methods Six research sites enrolled treatment-seeking men and women who reported any LUTS at a frequency more than “rarely” during the past month on the LUTS tool. At baseline, study participants underwent a standardized clinical evaluation and completed validated questionnaires; urological tests were performed, including pelvic/rectal examination, post-void residual, and urinalysis. Results A total of 545 women and 519 men were enrolled. The mean age was 58.8 ± 14.1 years. At baseline, nocturia, frequency, and a sensation of incomplete emptying were similar between men and women, whereas men experienced more voiding symptoms (90% vs. 85%, p=0.007), and women reported more urgency (85% vs. 66%, p<0.001). Women also reported more urinary incontinence (any type) than men (82% vs. 51% p<0.001), which was predominantly mixed incontinence (57%). Men rarely reported stress incontinence (1%), but did have other urinary incontinence (44% post-void dribbling) or urgency incontinence (46%). Older participants had higher odds of reporting symptoms of nocturia and urgency. Conclusion In this large treatment-seeking cohort of men and women, LUTS varied widely by sex and age. Men reported more voiding symptoms and non-stress or urgency urinary incontinence, whereas women reported more incontinence overall and urgency. Older participants had greater odds of urgency and nocturia.

The degree of IF is associated with risk of eGFR decline across different types of proteinuric glomerulopathy, correlates with inflammatory and fibrotic gene expression, and may have predictive value in assessing risk of progression.

Objective To describe occurrence, recovery, and consequences of musculoskeletal injuries in women at-risk for childbirth-related pelvic floor injury at first vaginal birth. Study Design Evaluating Maternal Recovery from Labor and Delivery (EMRLD) is a longitudinal cohort design study of women recruited early post-birth and followed over time. We report here on 68 women who had birth-related risk factors for levator ani muscle injury, including long second stage, anal tears, and/or older maternal age, and who were evaluated by musculoskeletal magnetic resonance imaging at both 7-weeks and 8-months postpartum. We categorized magnitude of injury by extent of bone marrow edema, pubic bone fracture, levator ani muscle edema, and levator ani muscle tear. We also measured the force of levator ani muscle contraction, urethral pressure, pelvic organ prolapse, and incontinence. Results In this higher-risk sample, 66% (39/59) had pubic bone marrow edema, 29% (17/59) had subcortical fracture, 90% (53/59) levator ani muscle edema, and 41% (28/68) low-grade or greater levator ani tear 7-weeks postpartum. The magnitude of levator ani muscle tear did not substantially change by 8-months postpartum (p=0.86), but levator ani muscle edema and bone injuries showed total or near total resolution (p<.05). The magnitude of unresolved musculoskeletal injuries correlated with magnitude of reduced levator ani muscle strength and posterior vaginal wall descent (p<.05) but not with urethral pressure, volume of demonstrable stress incontinence, nor self-report of incontinence severity (p>.05). Conclusion Pubic bone edema and subcortical fracture and levator ani muscle injury are common when studied in women with certain risk factors. The bony abnormalities resolve, but levator tear does not, and is associated with levator weakness and posterior-vaginal wall descent.

As results from single center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the A2ALL-2 Consortium. Among other initiatives A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed pre-donation, and 3, 6, 12, and 24 months post-donation. Repeated measures regression models were used to examine social relationship and financial outcomes over time and identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were overall positive across post-donation time points, with nearly one-third reporting improved donor family and spousal/partner relationships and >50% reporting improved recipient relationships. However, the majority of donors reported cumulative out-of-pocket medical and non-medical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held non-professional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Objectives: To describe the relationship between metabolic factors and lower urinary tract symptoms (LUTS), overactive bladder syndrome (OAB) and urinary incontinence (UI). Methods: Adult male and female patients who presented to a clinician from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were recruited. Urinary symptoms (presence of OAB, any UI, stress UI (SUI), urgency UI (UUI), urgency, frequency, and nocturia) were assessed with the LUTS Tool. Metabolic factors assessed included central obesity (waist circumference, using the Adult Treatment Panel III, the International Diabetes Federation thresholds, and waist circumference as a continuous variable), general obesity (body mass index [BMI] as dichotomous or continuous variables), diabetes mellitus, hypertension, and dyslipidemia. Multivariable logistic regression was used to test for associations. Results: 920 participants were studied. In multivariable analyses, central obesity (per 10cm larger waist) was associated with higher odds of UI in both sexes (OR=1.16, p=0.008), SUI in females (OR=1.27, p=0.008), UUI in both sexes (OR=1.24, p=0.001), OAB in females (OR=1.248, p=0.003), as well as frequency and nocturia. General obesity (5-unit increase in BMI) was associated with UI, UUI, urgency and frequency in both sexes, and with SUI and OAB in females. We did not find associations between central or general obesity and OAB in males. Dyslipidemia was associated with nocturia ≥2. Conclusions: In patients, central and general obesity were key metabolic factors associated with UI in both males and females, and with OAB in females but not in males. The association between dyslipidemia and nocturia ≥2 needs further research.

Background Studies of liver donors’ psychosocial outcomes focus on the short-term and rely largely on quality-of-life measures not specific to donation. We sought to examine long-term donation effects on three psychosocial domains: perceived physical, emotional, and socioeconomic outcomes. Methods Individuals donating 3–10 years previously at nine centers were eligible for telephone surveys. Survey responses were examined descriptively. Cluster analysis was used to identify distinct donor groups based on response profiles across psychosocial domains. Potential predictors of response profiles were evaluated with regression analysis. Results 517 donors (66%) participated (M=5.8 years postdonation, SD=1.9). 15%–48% of donors endorsed current donation-related physical health problems and concerns, and 7%–60% reported socioeconomic concerns (e.g., insurance difficulties, financial expenditures). However, on average, donors experienced high psychological growth, and 90% felt positively about donation. Cluster analysis revealed five donor groups. One group showed high psychological benefit, with little endorsement of physical or socioeconomic concerns (15% of donors). Four groups showed less favorable profiles, with varying combinations of difficulties. The largest such group showed high endorsement of physical concerns and financial expenditures, and only modest psychological benefit (31% of donors). Men and non-Hispanic whites were most likely to have unfavorable response profiles (p<.01). Compared with donors aged 19–30, older donors were less likely to have unfavorable profiles; these differences were significant for donors aged >40–50 (p’s<.008). Conclusions Even many years postdonation, donors report adverse physical and socioeconomic effects, but positive emotional effects as well. Identification of response profiles and predictors may improve targeting of postdonation surveillance and care.