Citations

The ability to predict outcomes for individual patients would be a significant advance for not only counseling, but also identifying those for whom interventions may be needed. The goals of this study were to validate an existing risk prediction score that incorporates easily obtainable clinical factors and determine if histologic findings at 1-year surveillance biopsy and/or serum donor–specific alloantibody status could improve predictability of graft loss by 5 years. We retrospectively studied 1465 adults who received a solitary kidney transplant between January of 1999 and December of 2008 and had sufficiently detailed 5-year follow-up data for modeling. In this cohort, the Birmingham risk model (incorporating recipient factors at 1 year, including age, sex, ethnicity, renal function, proteinuria, and prior acute rejection) predicted death–censored and overall graft survival (c statistics =0.84 and 0.78, respectively). The presence of glomerulitis or chronic interstitial fibrosis (g and ci scores by Banff, respectively) on 1-year biopsy specimens independently correlated with graft loss by 5 years. Adding these variables to the model for death–censored graft loss increased predictability (c statistic =0.90), improved calibration (ability to stratify risk from high to low), and reclassified risk of failure in 29% of patients. Adding the presence of donor-specific alloantibody at 1 year did not improve predictability or reclassification but did improve calibration marginally. We conclude that, at 1 year after kidney transplant, a risk model of graft survival that incorporates clinical factors and histologic findings at surveillance biopsy is highly predictive of individual risk and well calibrated.

Background: Among patients treated nonoperatively for 1 year after anterior cruciate ligament (ACL) disruption, little is known about the frequency of ACL reconstruction within the first year of injury and the effect of age range, sex, and meniscal tears on the incidence of ACL reconstruction between 1 and 10 years after injury. Purpose: To (1) define the rate of delayed ACL reconstruction (between 1 and 10 years after injury) in a population-based cohort of isolated ACL tears and (2) evaluate predictive factors associated with delayed reconstruction. Study Design: Case-control study; Level of evidence, 3. Methods: The study included a population-based cohort of 1841 patients with new-onset, isolated ACL tears that occurred between January 1, 1990, and December 31, 2010. The complete medical records were reviewed to confirm diagnosis and collect data on clinical characteristics and details of subsequent ACL surgery. To evaluate the incidence of ACL reconstruction between 1 and 10 years after injury, landmark survival analysis was performed with a landmark set at 1 year after injury. Early and late predictors of ACL reconstruction were analyzed using Cox proportional hazards regression. Results: A total of 661 patients were treated nonoperatively for the first year after ACL tears. Over a mean 10 years of follow-up, 213 patients (32%) underwent ACL reconstruction between 1 and 10 years after injury. Young age (hazard ratio [HR], 0.55 per decade increase in age; 95% CI, 0.48-0.62) and meniscal tear at injury (HR, 1.48; 95% CI, 1.12-1.95) were significant predictors of undergoing delayed reconstruction. The rate of delayed ACL reconstruction decreased significantly over the study period ( P < .03). There was no association between sex (HR, 0.89; 95% CI, 0.67-1.16) and delayed ACL reconstruction. Among patients who had delayed ACL reconstruction, 40% experienced a secondary meniscal tear before surgery. Conclusion: In this study population of 1841 patients, 62% of patients received ACL reconstruction within 1 year of injury. Of patients treated nonoperatively for 1 year after ACL tears, 32% underwent delayed ACL reconstruction. Predictors of reconstruction beyond 1 year were young age (50% reduction in reconstruction per decade increased age) and baseline meniscal tear. Sex was not predictive for reconstruction beyond 1 year from injury.

Non‐invasive tests to identify age and early disease‐associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age‐ and sex‐stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal‐derived EVs in cell‐free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20–70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker–positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule‐intercalated cell and monocyte chemoattractant protein‐1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule‐1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility.

AbstractBackgroundThe duration of anticytomegalovirus (CMV) prophylaxis after lung transplantation (LT) varies among transplant centers.MethodsA retrospective review of CMV donor‐seropositive/recipient‐seronegative (D+/R−) and CMV recipient‐seropositive (R+) LT patients between January 2005 and September 2012 was performed. Starting January 2007, valganciclovir prophylaxis was given for at least 12 months (often lifelong) for CMV D+/R− and extended from three to six months for R+ LT patients. Risks of CMV infection and CMV disease, and mortality after LT, were assessed.ResultsA total of 88 LT patients were studied, including 32 CMV D+/R−, and 56 R+ patients. During the follow‐up period, 11 (12.5%) patients had asymptomatic CMV infection, and nine (10.3%) developed CMV disease. CMV disease (HR, 4.189; 95% CI: 1.672–10.495; p = 0.002) and CMV infection and disease (HR, 3.775; 95% CI: 1.729–8.240; p = 0.001) were significant risk factors for mortality. Overall, no significant difference was observed in rates of CMV infection or disease among LT recipients who received shorter vs. extended CMV prophylaxis.ConclusionsDespite extended prophylaxis, LT patients remain at risk of CMV infection and disease. CMV remains associated with increased mortality after transplantation.

Abstract Background Frailty in non‐transplant populations increases morbidity and mortality. Muscle wasting is an important frailty characteristic. Low body mass index is used to measure wasting, but can over‐ or underestimate muscle mass. Computed tomography ( CT ) software can directly measure muscle mass. It is unknown if muscle wasting is important in lung transplantation. Aim and Methods The aim of this single‐center, retrospective cohort study was to determine whether pre‐transplant low muscle mass (as measured by CT using Slice‐O‐matic software at L2–L3 interspace) was associated with post‐transplantation mortality, hospital and intensive care unit length of stay ( LOS ), duration of mechanical ventilation, or primary graft dysfunction. Lung transplant recipients from 2000 to 2012 with a CT scan less than six months prior to transplant were included. Univariate, multivariate, and Kaplan–Meier analyses were conducted. Results Thirty‐six patients were included. Those with low muscle index (lower 25th percentile) had a worse survival (hazard ratio = 3.83; 95% confidence interval 1.42–10.3; p = 0.007) and longer hospital LOS by an estimated 7.2 d (p = 0.01) when adjusted for age and sex as compared to those with higher muscle index. Conclusion Low muscle index at lung transplantation is associated with worse survival and increased hospital LOS .

AbstractIntroductionFew studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.MethodsWe included 464 cognitively normal, test‐naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51–71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow‐up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline.ResultsElevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test.DiscussionElevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.

Objectives To determine the association between multiple chronic conditions and risk of incident mild cognitive impairment ( MCI ) and dementia. Design Prospective cohort study. Setting Olmsted County, Minnesota. Participants Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of Aging ( MCSA ). Measurements Participants were randomly selected from the community, evaluated by a physician, and underwent neuropsychometric testing at baseline and at 15‐month intervals to assess diagnoses of MCI and dementia. Information on International Classification of Diseases, Ninth Revision codes for chronic conditions in the 5 years before enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions, and the association between multimorbidity and MCI and dementia was examined using Cox proportional hazards models. Results Of 2,176 cognitively normal participants (mean age ± standard deviation 78.5 ± 5.2; 50.6% male), 1,884 (86.6%) had multimorbidity. The risk of MCI or dementia was higher in persons with multimorbidity (hazard ratio ( HR ) = 1.38, 95% confidence interval ( CI ) = 1.05–1.82) than in those with one or no chronic condition. The HR was of greater magnitude in persons with four or more conditions ( HR = 1.61, 95% CI = 1.21–2.13) than in those with two or three conditions ( HR = 1.03, 95% CI = 0.76–1.39) and for men with multimorbidity( HR = 1.53, 95% CI = 1.01–2.31) than for women with multimorbidity ( HR = 1.20, 95% CI = 0.83–1.74), compared to those with one or no chronic condition. Conclusion In older adults, having multiple chronic conditions is associated with greater risk of MCI and dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late‐life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI and dementia.