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Utilization of hepatitis C (HCV) viremic kidneys is increasing in the United States. We examined racial disparity in this utilization using UNOS/OPTN data (2014-2020) and mixed effects models adjusting for donor/recipient/center factors. Included in the study were 58,786 adults receiving a deceased donor kidney transplant from 191 centers. Two thousand six hundred thirteen (4%) received kidneys from HCV-viremic donors. Of these, 1598 (61%) were HCV seronegative and 1015 (49%) were HCV seropositive. Among seronegative recipients, before adjusting for waiting time and education, Blacks (OR 0.69, 95%CI (0.60, 0.80)), Hispanics (OR 0.63, 95%CI (0.51, 0.79)), and Asians (OR 0.69, 95%CI (0.53, 0.90)) were less likely than Whites to receive HCV-viremic kidneys. In final models, effect of race was attenuated. Notably, shorter waiting time (OR 0.65, 95%CI (0.63, 0.67)) and increasing educational level (grade school less likely compared to high school OR 0.67, 95% CI (0.49, 0.92) and college more likely than high school (OR 1.16 95% CI (1.02, 1.31)) were associated with receipt of HCV-viremic kidneys. Among HCV-seropositive recipients, recipient race was not independently associated with receipt of HCV-viremic kidneys; however, centers with larger populations of Black waitlisted patients were more likely to utilize HCV-viremic kidneys (OR 1.71, 95%CI (1.20, 2.45)) compared to other centers. Our results suggest recipient race does not independently determine who receives HCV-viremic kidneys; however, other underlying factors including waiting time, education (among seronegative), and center racial mix (among seropositive) contribute to the current differential distribution of HCV-viremic kidneys among races., (© 2022. W. Montague Cobb-NMA Health Institute.)

Introduction: Kidney transplant candidates are occasionally found during the pre-transplant evaluation to have a suspicious mass in a native kidney. Further work-up and management of such a mass may delay transplantation for several months, which may create logistic barriers to transplant, particularly if there are timing constraints of the donor. In this study, we report our experience with simultaneous living donor kidney transplant and laparoscopic native nephrectomy, where the indication for nephrectomy was a suspicious lesion. Methods: We performed a retrospective review of patients who underwent simultaneous kidney transplant and native nephrectomy using prospectively collected data. We analyzed relevant patient characteristics, surgical details, pathologic results, and long-term follow-up. Results: We identified 16 patients who underwent simultaneous living donor kidney transplantation and laparoscopic native nephrectomy at our institution between 2013 and 2018. Ten (62.5%) patients were found to have renal-cell carcinoma (RCC) on the final pathology. No patients had recurrent RCC, at a median follow-up of 4 years. Conclusion: For patients who are planning to undergo a living donor kidney transplant and are found to have a small mass that is suspicious for RCC, a simultaneous living donor kidney transplant and laparoscopic native nephrectomy is a possible approach in selected patients.

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Peripheral nerve injuries can be devastating complications of surgery, potentially resulting in severe functional disability and decreased quality of life. Long surgeries with considerable tissue manipulation, for example, liver transplantation, may present increased risk; however, neuropraxia in transplantation has not been well investigated., Materials and Methods: This is a retrospective study of all adult patients undergoing liver transplantation at a large academic center between January 2013 and December 2015. Descriptive analyses, logistic regressions, and forward selection procedures were used to determine the odds of developing neuropraxia and associated factors., Results: Of the 283 liver recipients, the mean age was 55.8 y, 35.1% were female, 65.6% were Caucasian, 8.9% were African American, 16.7% were Hispanic, and mean model for end-stage liver disease sodium score at transplant was 24.2 ± 10.9. The underlying etiology was alcohol (26.2%), hepatitis C (34.8%), nonalcoholic steatohepatitis (13.1%), and other (14.2%). The incidence of neuropraxia after liver transplantation was 8.3% (n = 25), with 60% (n = 16) upper extremities, 82% left sided, and 84% male. There was no difference in age, race, body mass index, hypertension, diabetes, hyperlipidemia, or smoking in those with neuropraxia versus those without. In multivariate analysis, neuropraxia was significantly associated with male gender, lower model for end-stage liver disease score, and longer duration of surgery (P < 0.05). Symptoms lasted median 5 d, with a wide range up to 187 d. Neuropraxia-specific treatment (physical therapy or medications) was required in 32% (n = 9)., Conclusions: Peripheral nerve injuries are an unexplored complication of liver transplantation. Although transient, a high number (8.2%) of patients developed neuropraxia, negatively affecting their ability for recovery. Exploration of mechanisms for minimizing risk and intraoperative detection and prevention should be considered to mitigate this complication., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies., Methods: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate., Results: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients., Conclusions: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objective: Outcomes of infrainguinal bypass surgery (IBS) in patients with renal transplants are largely undescribed. This study evaluated perioperative and long-term outcomes of IBS using autogenous and prosthetic conduits in a large population-based cohort of renal transplantation patients., Methods: A retrospective review of all renal transplantation patients who underwent IBS between January 2007 and December 2011 in the United States Renal Data System was performed. Univariable, Kaplan-Meier, multivariable logistic, and Cox regression analyses were employed to evaluate 30-day postoperative (graft failure, limb loss, conduit infection, and death) and long-term (primary patency, primary assisted patency, secondary patency, limb salvage, and mortality) outcomes., Results: There were 1048 IBSs performed (autogenous, 68%; prosthetic, 32%), predominantly for critical limb ischemia (70%). Of these, 480 (46%) were femoral-popliteal, 330 (31%) were femoral-tibial, and 238 (23%) were popliteal-tibial bypasses. Comparing autogenous vs prosthetic conduits, primary patency was 33% vs 28% (P = .22), primary assisted patency was 38% vs 31% (P = .13), secondary patency was 48% vs 53% (P = .67), limb salvage was 53% vs 63% (P = .73), and patient survival was 47% vs 51% (P = .88), all at 5 years. Risk-adjusted analyses demonstrated higher primary assisted patency (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.06-1.66; P = .012), secondary patency (aHR, 1.33; 95% CI, 1.02-1.74; P = .034), and limb salvage (aHR, 1.35; 95% CI, 1.02-1.80; P = .037) for autogenous compared with prosthetic bypasses. There was no difference in mortality of patients who received autogenous vs prosthetic conduits., Conclusions: We have presented postoperative and long-term outcomes of IBS in renal transplantation patients. Autogenous bypasses outperform prosthetics with regard to primary assisted patency, secondary patency, and limb salvage. Given the modest survival advantage conferred by renal transplantation, maximum efforts should be made to create bypasses with autogenous conduits when it is feasible. These results should inform the patient's and surgeon's expectations in planning of IBS for these patients., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients often have an incomplete understanding of the levels of training and roles of the various surgical providers in teaching hospitals, leading to patient confusion and dissatisfaction., Methods: Pre-intervention discharge surveys were administered to gastrointestinal surgery inpatients (10/2016-02/2017) to evaluate sentiments regarding their surgical team. During the intervention period (02/2017-05/2017), patients at admission received "facesheets" containing team member profiles, photos, training level, and roles. These patients were evaluated using the survey, and pre- and post-intervention scores compared., Results: 153 pre- and 100 post-intervention surveys were collected. There was a significant increase in patients reporting it was important to know the surgical team members and that they knew team member roles (p ≤ 0.05). Scores in every domain of the satisfaction survey improved in the post-intervention period, although not reaching statistical significance., Conclusions: Improving how patients perceive their interactions with their surgical team has implications on patient satisfaction and hospital quality metrics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the United States, the Centers for Medicare and Medicaid Services (CMS) use Systems Improvement Agreements (SIAs) to require transplant programs repeatedly flagged for poor-performance to improve performance or lose CMS funding for transplants. We identified 14 kidney transplant (KT) programs with SIAs and 28 KT programs without SIAs matched on waitlist volume and characterized kidney acceptance using SRTR data from 12/2006-3/2015. We used difference-in-differences linear regression models to identify changes in acceptance associated with an SIA independent of program variation and trends prior to the SIA. SIA programs accepted 26.9% and 22.1% of offers pre- and post-SIA, while non-SIA programs accepted 33.9% and 44.4% of offers in matched time periods. After adjustment for donor characteristics, time-varying waitlist volume, and secular trends, SIAs were associated with a 5.9 percentage-point (22%) decrease in kidney acceptance (95% CI: -10.9 to -0.8, P = .03). The decrease in acceptance post-SIA was more pronounced for KDPI 0-40 kidneys (12.3 percentage-point decrease, P = .007); reductions in acceptance of higher KDPI kidneys occurred pre-SIA. Programs undergoing SIAs substantially reduced acceptance of kidney offers for waitlisted candidates. Attempts to improve posttransplant outcomes might have the unintended consequence of reducing access to transplantation as programs adopt more restrictive organ selection practices., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

While studies demonstrate poor outcomes of lower extremity revascularization in patients with end-stage renal disease, little is known about results in renal transplant patients. We analyzed 2-year primary patency and limb salvage outcomes and associated risk factors of transplant (n = 202) and nontransplant patients (n = 25 274) in the Vascular Quality Initiative database undergoing infrainguinal bypass from 2003 to 2016. Multivariable Cox regression analysis and coarsened exact matching with many-to-one were used. Transplant patients were more likely to have critical limb ischemia and revascularization of more distal arteries and to receive vein conduits. Primary patency was similar between transplant and nontransplant patients at 1 year (80.8% vs 77.5%) and 2 years (67.9% vs 63.7%, P = .079). Amputation-free survival was higher for nontransplant patients (1 year: 82.4% vs 75.3%, 2 years: 68.8% vs 58.2%, P = .0060), although overall survival was equivalent (2 years: 84.6% vs 87.2%, 4 years: 75.9% vs 79.6%, P = .35). Risk factors for primary patency loss included being female, critical limb ischemia, prior bypass, and distal bypass. Age, diabetes, prior contralateral amputation, critical limb ischemia, prosthetic conduit, and more distal bypass were associated with limb loss. This is the largest series of infrainguinal revascularization in transplant patients. Outcomes for transplant patients are not inferior, and aggressive approaches at limb salvage are justifiable in appropriately selected patients., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In multiple studies, chronic renal insufficiency has been associated with increased risk of periprocedural stroke, cardiac complications, and death following carotid revascularization. Renal transplantation has been shown to reduce cardiovascular risk and improve survival; outcomes after carotid revascularization in renal transplant patients however are unknown. In this study, we evaluate periprocedural and long-term risks after carotid endarterectomy (CEA) and carotid artery stenting (CAS) in a cohort of renal transplant patients., Methods: We studied all renal transplant patients in the United States Renal Data System who underwent CEA or CAS between January 2006 and December 2011. Patient outcomes were determined by linking with the Medicare database. Propensity score matched logistic and cox regression analyses were employed to evaluate perioperative stroke, myocardial infarction (MI), and death and long-term stroke and death., Results: Of the 462 revascularizations for asymptomatic carotid artery stenosis between 2006 and 2011, 387 (84%) were CEA and 75 (16%) were CAS. The 2 groups did not differ in age, gender, sex, race, or baseline medical characteristics. There was no significant difference in perioperative stroke, MI, or death rates in the CEA cohort (4.7%, 4.4%, and 1.3%, respectively) compared with the CAS cohort (5.3%, 2.7%, and 4.0%, respectively). Stroke-free survival for CEA versus CAS was 93% vs. 92% at 1 year, 90% vs. 87% at 2 years, 88% vs. 87% at 3 years, and 84% vs. 82% at 4 years (P = 0.81). Overall patient survival for CEA versus CAS was 89% vs. 88% at 1 year, 77% vs. 75% at 2 years, 66% for both at 3 years, and 53% vs. 48% at 4 years (P = 0.68). In propensity score matched Cox regression analysis, there was no difference in risk of perioperative stroke or MI or in long-term stroke or death for CAS compared with CEA., Conclusions: This is the first study to evaluate outcomes following CEA and CAS in renal transplant patients. The incidence of perioperative complications in this group is higher than the maximum recommended by the Society of Vascular Surgery, and the benefits of revascularization may be outweighed by the excess periprocedural morbidity and reduced life expectancy of these patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to investigate the prognostic significance of early (30-day) hospital readmission (EHR) on mortality after pancreatectomy., Methods: Using a prospectively collected institutional database linked with a statewide dataset, we evaluated the association between EHR and overall mortality in all patients undergoing pancreatectomy at our tertiary institution (2005 to 2010)., Results: Of 595 pancreatectomy patients, EHR occurred in 21.5%. Overall mortality was 29.4% (median follow-up 22.7 months). Patients with EHR had decreased survival compared with those who were not readmitted (P = .011). On multivariate analysis adjusting for baseline group differences, EHR for gastrointestinal-related complications was a significant independent predictor of mortality (hazard ratio 2.30, P = .001)., Conclusions: In addition to known risk factors, 30-day readmission for gastrointestinal-related complications following pancreatectomy independently predicts increased mortality. Additional studies are necessary to identify surgical, medical, and social factors contributing to EHR, as well as interventions aimed at decreasing postpancreatectomy morbidity and mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181)., Methods and Findings: Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age., Conclusions/significance: Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential.

Background: Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome., Methods and Findings: CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively., Conclusions: Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions.

Background: Disease-modifying therapies for Alzheimer's disease (AD) would be most effective during the preclinical stage (pathology present, cognition intact) before significant neuronal loss occurs. Therefore, biomarkers that detect AD pathology in its early stages and predict dementia onset and progression will be invaluable for patient care and efficient clinical trial design., Methods: AD-associated changes in cerebrospinal fluid (CSF) were measured using two-dimensional difference gel electrophoresis and liquid chromatography tandem mass spectrometry. Subsequently, CSF YKL-40 was measured by enzyme-linked immunosorbent assay in the discovery cohort (n = 47), validation cohort (n = 292) with paired plasma samples (n = 237), frontotemporal lobar degeneration (n=9) [corrected], and progressive supranuclear palsy (PSP; n = 6). Immunohistochemistry was performed to identify source(s) of YKL-40 in human AD brain., Results: Discovery and validation cohorts, showed higher mean CSF YKL-40 in very mild and mild AD-type dementia (Clinical Dementia Rating [CDR] 0.5 and 1) versus control subjects (CDR 0) and PSP subjects. Importantly, CSF YKL-40/Aβ42 ratio predicted risk of developing cognitive impairment (CDR 0 to CDR > 0 conversion), as well as the best CSF biomarkers identified to date, tau/Aβ42 and p-tau 181/Aβ42. Mean plasma YKL-40 was higher in CDR 0.5 and 1 versus CDR 0, and correlated with CSF levels. YKL-40 immunoreactivity labeled astrocytes near a subset of amyloid plaques, implicating YKL-40 in the neuroinflammatory response to Aβ deposition., Conclusions: These data demonstrate that YKL-40, a putative indicator of neuroinflammation, is elevated in AD and, together with Aβ42, has potential prognostic utility as a biomarker for preclinical AD., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Although a battery of neuropsychological tests is often used in making a clinical diagnosis of Alzheimer's disease (AD), definitive diagnosis still relies on pathological evaluation at autopsy. The identification of AD biomarkers may allow for a less invasive and more accurate diagnosis as well as serve as a predictor of future disease progression and treatment response. Importantly, biomarkers may also allow for the identification of individuals who are already developing the underlying pathology of AD such as plaques and tangles yet who are not yet demented, i.e. "preclinical" AD. Attempts to identify biomarkers have included fluid and imaging studies, with a number of candidate markers showing significant potential. More recently, better reagent availability and novel methods of assessment have further spurred the search for biomarkers of AD. This review will discuss promising fluid and imaging markers to date.

Stabilization of proteins is a long-sought objective. Targeting the unfolded state interactions of a protein is not a method used for this purpose, although many proteins are known to contain such interactions. The N-terminal domain of ribosomal protein L9 (NTL9) has a lysine residue at position 12, which makes strong non-native interactions in the unfolded state. Substitution of a d-alanine for G34 in NTL9 is known to stabilize the protein by reducing the entropy of the unfolded state. Here we combine these two mutations to design a hyperstable protein. The structure of the variant is the same as that of wild-type as judged by 2D NMR. The variant is hyperstable as judged by denaturation experiments, where complete thermal unfolding of the protein does not occur in native buffer.