Risk factors for renal dysfunction after isolated intestinal transplantation.

INTRODUCTION: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. METHODS: This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p < .1 in univariate analysis were considered for multivariable modeling. RESULTS: Thirty-three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (ß = -.77, p < .01) and stoma days (ß = -.06, p < .01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. CONCLUSIONS: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.

Tacrolimus time-in-therapeutic range is associated with freedom from acute rejection and graft failure following intestinal transplantation.

BACKGROUND: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes. METHODS: This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile. RESULTS: 47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33). CONCLUSION: The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.

Surveillance of high-risk individuals for pancreatic cancer with EUS and MRI: A meta-analysis.

BACKGROUND/OBJECTIVES: Consensus guidelines recommend surveillance of high-risk individuals (HRIs) for pancreatic cancer (PC) using endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). This study aims to assess the yield of PC surveillance programs of HRIs and compare the detection of high-grade dysplasia or T1N0M0 adenocarcinoma by EUS and MRI. METHODS: The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRIs for PC. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-grade dysplasia or T1N0M0 adenocarcinoma, and all pancreatic adenocarcinoma were recorded. Weighted pooled proportions of outcomes detected were compared between EUS and MRI using random effects modeling. RESULTS: A total of 1097 studies were reviewed and 24 were included, representing 2112 HRIs who underwent imaging. The weighted pooled proportion of focal pancreatic abnormalities detected by baseline EUS (0.34, 95% CI 0.30-0.37) was significantly higher (p = 0.006) than by MRI (0.31, 95% CI 0.28-0.33). There were no significant differences between EUS and MRI in detection of other outcomes. The overall weighted pooled proportion of patients with high-grade dysplasia or T1N0M0 adenocarcinoma detected at baseline (regardless of imaging modality) was 0.0090 (95% CI 0.0022-0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-grade dysplasia or T1N0M0 adenocarcinoma. CONCLUSIONS: Surveillance programs are successful in detecting high-risk precursor lesions. No differences between EUS and MRI were noted in the detection of high-grade dysplasia or T1N0M0 adenocarcinoma, supporting the use of either imaging modality.

Safety of direct-acting oral anticoagulants relative to warfarin in a matched cohort of liver transplant recipients.

Despite increasingly widespread utilization of direct-acting oral anticoagulants (DOACs), there remains limited experience with the use of these agents following liver transplantation. We performed a single-center, retrospective review of liver transplant recipients prescribed DOACs or warfarin between January 2014 and January 2018. Patients receiving DOACs were matched with warfarin-treated controls based on discrete clinical parameters and followed from the time of anticoagulant prescription, until treatment discontinuation or study conclusion. The primary endpoint for this review was the incidence of clinically relevant major or non-major bleeding among the treatment groups. Twenty-seven patients prescribed DOACs were identified for inclusion in the review, of which 20 could be matched with suitable warfarin controls. At the conclusion of the study, warfarin-treated patients had a significantly higher incidence of clinically relevant bleeding (45% vs 15%; P = .01). No statistically significant differences were found in the rate of new or recurrent thrombotic events. Multivariable logistic regression demonstrated that warfarin treatment was associated with a significantly higher odds of a bleeding event compared to treatment with a DOAC (OR = 6.9; 95% CI, 1.1-44.6). DOAC use appears relatively safe compared with warfarin in select liver transplant recipients. Patient-specific factors still bear consideration when selecting between the various anticoagulant options.

Utilization of peritoneal dialysis in the United States: Reasons for underutilization, specifically in New York State and the boroughs of New York City.

Peritoneal dialysis (PD) is currently underutilized in the United States (US), even within resource-rich neighborhoods. We analyzed data from US Renal Data Service to determine PD utilization within the US, New York State (NYS), selected boroughs within New York City (NYC), and Boston, Massachusetts. We then compared the odds of selecting PD with hemodialysis (HD) and analyzed how diabetes mellitus status, age >65 years, gender, and race influenced PD utilization between 2010 and 2016. We then compared a high-volume PD center (HVC) with a low-volume PD center (LVC). The odds of starting PD vs HD were as follows: Brooklyn 0.30 (0.25-0.36; <0.0001), Bronx 0.56 (0.47-0.67; <0.0001), Queens 0.66 (0.54-0.80; <0.0001), and Manhattan 0.61 (0.52-0.71; <0.0001). In 2016, the odds of starting PD compared with the rest of the US were as follows: Brooklyn 0.14 (0.08-0.22; <0.0001), Bronx 0.39 (0.27-0.56; <0.0001), Queens 0.32 (0.23-0.45; <0.0001), Manhattan 0.54 (0.36-0.79; 0.002), and Boston 0.89 (0.58-1.4; 0.624). Analysis of influencing factors showed that only age >65 significantly (<0.0001) influenced PD modality selection in Brooklyn and Boston. Differences between HVC and LVC in terms of modality transition, peritonitis rate, or provider:patient ratio were not statistically significant. Factors that influence PD utilization in urban neighborhoods are discussed and remediation measures are proposed.

Blood Pool Segmentation Results in Superior Virtual Cardiac Models than Myocardial Segmentation for 3D Printing.

The method of cardiac magnetic resonance (CMR) three-dimensional (3D) image acquisition and post-processing which should be used to create optimal virtual models for 3D printing has not been studied systematically. Patients (n = 19) who had undergone CMR including both 3D balanced steady-state free precession (bSSFP) imaging and contrast-enhanced magnetic resonance angiography (MRA) were retrospectively identified. Post-processing for the creation of virtual 3D models involved using both myocardial (MS) and blood pool (BP) segmentation, resulting in four groups: Group 1-bSSFP/MS, Group 2-bSSFP/BP, Group 3-MRA/MS and Group 4-MRA/BP. The models created were assessed by two raters for overall quality (1-poor; 2-good; 3-excellent) and ability to identify predefined vessels (1-5: superior vena cava, inferior vena cava, main pulmonary artery, ascending aorta and at least one pulmonary vein). A total of 76 virtual models were created from 19 patient CMR datasets. The mean overall quality scores for Raters 1/2 were 1.63 ± 0.50/1.26 ± 0.45 for Group 1, 2.12 ± 0.50/2.26 ± 0.73 for Group 2, 1.74 ± 0.56/1.53 ± 0.61 for Group 3 and 2.26 ± 0.65/2.68 ± 0.48 for Group 4. The numbers of identified vessels for Raters 1/2 were 4.11 ± 1.32/4.05 ± 1.31 for Group 1, 4.90 ± 0.46/4.95 ± 0.23 for Group 2, 4.32 ± 1.00/4.47 ± 0.84 for Group 3 and 4.74 ± 0.56/4.63 ± 0.49 for Group 4. Models created using BP segmentation (Groups 2 and 4) received significantly higher ratings than those created using MS for both overall quality and number of vessels visualized (p < 0.05), regardless of the acquisition technique. There were no significant differences between Groups 1 and 3. The ratings for Raters 1 and 2 had good correlation for overall quality (ICC = 0.63) and excellent correlation for the total number of vessels visualized (ICC = 0.77). The intra-rater reliability was good for Rater A (ICC = 0.65). Three models were successfully printed on desktop 3D printers with good quality and accurate representation of the virtual 3D models. We recommend using BP segmentation with either MRA or bSSFP source datasets to create virtual 3D models for 3D printing. Desktop 3D printers can offer good quality printed models with accurate representation of anatomic detail.

Prospective, multicenter study of ventricular assist device infections.

BACKGROUND: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. METHODS AND RESULTS: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). CONCLUSIONS: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Occurrence of steam pops during irrigated RF ablation: novel insights from microwave radiometry.

BACKGROUND: The disparity between catheter and tissue temperatures during irrigated RF ablation frustrates one's ability to predict steam pops. Microwave radiometry allows for "volumetric" temperature assessment-i.e., within a circumscribed volume around the catheter tip-permitting, direct assessment of temperature during ablation. The aim of this study was to examine (i) the ability of microwave radiometry to predict steam pops, and (ii) compare this to traditional parameters such as power, catheter temperature, and impedance. METHODS AND RESULTS: Irrigated RF ablation was performed in 8 sheep using the Tempasure ablation catheter in all chambers. Power, impedance, catheter tip, and volumetric temperature were continually monitored. Ablation was terminated after a pop or at 60 seconds. A pop was defined as an audible or visualized pop (intracardiac echocardiography). Predictors of pops were determined by univariate and multivariate GEE logistic regression modeling. A total of 48 pops occurred during 143 lesions applied at 20-50 W. There was no association between the chamber of the heart and the occurrence of pops. The rate of rise of volumetric temperature (greater than 1.5 °C/s) was the single best predictor of pops (OR: 88.8 [95% CI: 12-604], P < 0.0007). Pops only occurred above a maximum volumetric temperature threshold of 89 °C. CONCLUSIONS: During irrigated RF ablation, steam pop occurrence can be predicted by both, the rate of rise and the maximum volumetric temperature measured by microwave radiometry.

Staphylococcus epidermidis colonization is highly clonal across US cardiac centers.

BACKGROUND: Little is known about the clonality of Staphylococcus epidermidis in the United States, although it is the predominant pathogen in infections involving prosthetic materials, including ventricular assist devices (VADs). METHODS: Seventy-five VAD recipients at 4 geographically diverse US cardiac centers were prospectively followed up to 1 year of VAD support. The anterior nares, sternum, and (future) driveline exit site were cultured for S. epidermidis before VAD insertion and at 7 times after surgery. Infection isolates were also collected. Isolates were typed by pulsed-field gel electrophoresis. A subset underwent susceptibility testing and staphylococcal chromosomal cassette mec and multilocus sequence typing. RESULTS: A total of 1559 cultures yielded 565 S. epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal types as defined by pulsed-field gel electrophoresis. These clones were identified in up to 27 people distributed across all 4 cardiac centers. They caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic resistant than were less prevalent isolates (eg, 79% vs 54% methicillin resistant; P = .0021). CONCLUSIONS: This study revealed that healthcare-associated S. epidermidis infection is remarkably clonal. We describe S. epidermidis clones that are highly resistant to antibiotics distributed across US cardiac centers. These clones may have determinants that enhance transmissibility, persistence, or invasiveness. Clinical Trials Registration. NCT01471795.

Direction of preoperative ventricular shunting affects ventricular mechanics after Tetralogy of Fallot repair.

BACKGROUND: Tetralogy of Fallot (TOF) typically results in clinical cyanosis or volume overload of the left ventricle (LV), depending on the direction and magnitude of shunting across the ventricular septal defect (VSD). The present study examines the effects of surgical TOF repair on LV mechanics and compares these changes between patients with VSD shunts that are predominantly right-to-left (R-L; "blue TOF") and those with VSD shunts that are predominantly left-to-right (L-R; "pink TOF"). METHODS AND RESULTS: Eleven patients (6 R-L and 5 L-R) 4.3 to 18.4 months old (median 7.1 months old) were studied. LV end-diastolic area (EDA) was calculated from transesophageal echocardiograms obtained during initiation and weaning of cardiopulmonary bypass. LV end-diastolic pressure was measured by micromanometer. Compliance was assessed by end-diastolic pressure-area curves. Contractility was assessed from preload recruitable stroke work by the stroke work-versus-LV EDA relation. VSD shunt direction was determined by preoperative Doppler echocardiography. Changes in LV function at the conclusion of cardiopulmonary bypass included decreased stroke area (from 6.6 +/- 0.9 to 4.1 +/- 0.4 cm(2)/m(2), P=0.012) and ejection fraction (from 55 +/- 2% to 41 +/- 3%, P<0.001). LV EDA at a common pressure in 8 patients decreased (from 10.4 +/- 1.4 to 7.6 +/- 1.2 cm(2)/m(2), P=0.003), which suggests a decrease in ventricular compliance. Additionally, the end-diastolic pressure-area curves shifted to the left in all patients. Preload recruitable stroke work decreased (from 34.8 +/- 2.4 to 21.8 +/- 2.6 mm Hg, P=0.007), which demonstrates a decrease in ventricular contractility. When separated by preoperative shunt direction, LV EDA increased in R-L patients by 0.9+/-0.5 cm(2)/m(2) postoperatively but decreased in L-R patients by 4.3 +/- 0.8 cm(2)/m(2) (P<0.001). Area ejection fraction decreased in all patients independent of shunting or change in LV EDA. CONCLUSIONS: LV diastolic and systolic function are depressed after TOF repair. Mechanical effects of the VSD patch and myocardial depressant effects of ischemia and reperfusion during surgery probably contribute to the observed changes in LV mechanics. Different effects of surgical repair on LV preload in pink and blue TOF also contribute to the spectrum of clinical results observed after surgery.

Simultaneous variation of ventricular pacing site and timing with biventricular pacing in acute ventricular failure improves function by interventricular assist.

The goal of this work was to investigate the hemodynamic effects of simultaneous left ventricular (LV) pacing site (LVPS) and interventricular pacing delay (VVD) variation with biventricular pacing (BiVP) during acute LV failure. Simultaneously varying LVPS and VVD with BiVP has been shown to improve hemodynamics during acute right ventricular (RV) failure. However, effects during acute LV failure have not been reported. In six open-chest pigs, acute LV volume overload was induced by regurgitant flow via an aortic-LV conduit. Epicardial BiVP was implemented with right atrial and ventricular leads and a custom LV pacing array. Fifty-four LVPS-VVD combinations were tested in random order. Cardiac output was evaluated by aortic flow probe, ventricular systolic function by maximum rate of ventricular pressure change, and mechanical interventricular synchrony by normalized RV-LV pressure diagram area. Simultaneous LVPS-VVD variation improved all measures of cardiac function. The observed effect was different for each functional index, with evidence of LVPS-VVD interaction. Compared with effects of LVPS-VVD variation in a model of acute RV failure, hemodynamic changes were markedly different. However, in both models, maximum rate of ventricular pressure change of the failing ventricle was improved with synchronous interventricular contraction, suggesting that, in acute ventricular failure, BiVP can recruit the unstressed ventricle to support systolic function of the failing one. Thus simultaneously varying LVPS and VVD with BiVP during acute ventricular failure can improve cardiac function by "interventricular assist", with hemodynamic effects dependent on the type of failure. This supports the potential utility of temporary BiVP for the treatment of acute ventricular failure commonly seen after cardiac surgery.

Outer Retinal Thickness and Fundus Autofluorescence in Geographic Atrophy.

PURPOSE: Most studies of fundus autofluorescence (FAF) in geographic atrophy (GA) have been nonquantitative, with inadequate registration of image modalities. Furthermore, as pointed out in the recent Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT, it is unclear whether decreased FAF would be correlated exclusively with a single category of OCT-defined atrophy. We sought to determine how FAF intensity in eyes with GA correlates with structural changes of the outer retina and choroid as seen on co-registered spectral domain OCT (SD-OCT) images. DESIGN: Retrospective cross-sectional. PARTICIPANTS: Twenty eyes of 11 patients with GA secondary to non-neovascular age-related macular degeneration (AMD). METHODS: Spectral domain OCT and FAF images for each eye were co-registered using MATLAB (MathWorks Inc, Natick, MA). On B-scans, the choroid, retinal pigment epithelium (RPE), photoreceptor (PR) layer, and outer nuclear layer (ONL) were segmented. Regions of interest (ROIs) including all atrophic and border regions were selected manually on the FAF scans. Regions of interest were subdivided into quartiles of FAF level to correlate with retinal thickness measurements taken along the B-scans. Mean choroid, RPE, PR, and ONL thicknesses were compared across quartiles using an analysis of variance factorial design testing for interaction effects, adjusted for repeated measures (on both eyes) with a within-subjects factor. RESULTS: Seventeen eyes of 10 patients were selected for analysis. The mean choroidal thicknesses were not significantly different across FAF quartiles, but the overall differences in mean RPE, PR layer, and ONL thicknesses across quartiles were statistically significant (analysis of variance, P < 0.001, P < 0.001, and P = 0.015, respectively). Post hoc analysis demonstrated significant differences in thickness among quartiles 1, 2, and 3 for the RPE and PR layers (Tukey, P < 0.01 in each case). The FAF quartiles within GA did not correlate exclusively with single categories of Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration-defined atrophy. CONCLUSIONS: Not only RPE but also PR layer thickness on SD-OCT varies significantly with FAF levels in GA. This suggests that although the RPE cells are losing thickness and function, evidenced by decreased FAF from fluorophores, delicate PR cells also succumb early in the disease process. These relationships should be pursued as a possibly better-detailed mechanism in GA.

Ventricular diastolic stiffness predicts perioperative morbidity and duration of pleural effusions after the Fontan operation.

BACKGROUND: We validated the clinical relevance of ventricular stiffness by examining surgical morbidity in children with univentricular hearts undergoing Fontan operation. We hypothesized that ventricular stiffness affects Fontan morbidity, particularly duration of pleural effusions. METHODS AND RESULTS: Sixteen children with right ventricular (RV) (n =11) or left ventricular (LV) (n =5) dominance were studied intraoperatively at a median age of 3.3 years (1.8 to 5.1). Transesophageal long-axis echocardiograms and ventricular pressure by micromanometer provided end-diastolic pressure (P) area (A) relations during initiation and conclusion of cardiopulmonary bypass. Curve fitting to the equation P=alphae(betaA) defined the ventricular stiffness constant, beta. Changes in beta and clinical correlations were examined. Ventricular stiffness increased after bypass in patients with complete pre-bypass and post-bypass data (n =11, P=0.023, mixed models methodology). Pre-bypass beta correlated well with duration of chest tube (CT) drainage (r=0.90, n =16), net perioperative fluid balance (r=0.71, n=14), and length of stay (LOS) (r=0.81, n =16). CT duration and LOS also correlated significantly with post-bypass beta (r=0.77 for both, n=11), but insignificantly with preoperative catheterization pressures. CONCLUSIONS: Intraoperative beta predicts duration of CT drainage, net perioperative fluid balance, and LOS after the Fontan operation. These observations could improve risk stratification and clinical management of children at high-risk undergoing the Fontan operation.

Induction of inflammatory bowel disease accelerates adenoma formation in Min +/- mice.

BACKGROUND: The accelerated incidence of colorectal carcinoma in individuals with inflammatory bowel disease suggests that cellular perturbation triggered by chronic inflammation is linked to the development of dysplasia and neoplastic transformation. To test the mechanistic links between these processes, we employed the following murine strains: (1) multiple intestinal neoplasia (Min) +/- mice, bearing a mutation in the adenomatous polyposis coli (APC) gene; (2) mice deficient in interleukin 10 (IL-10), which normally develop enterocolitis; and (3) Min +/-/IL-10 null mice, first developed in our laboratory. METHODS: Mice with either parental strain or the cross were sacrificed at time points ranging from 10 to 30 weeks of age. The small bowel and colon of 170 IL-10 null mice, 31 Min +/- mice, and 120 Min +/-/IL-10 null mice were examined microscopically. RESULTS: The number of flat adenomas was increased in the colons of the Min +/-/IL-10-/- mice, compared with the Min +/- mice (P = .0005). Neither colitis-type dysplasia nor carcinoma was increased in the Min +/-/IL-10 -/-, compared with the IL-10 null mice (P = .18). Mice deficient in IL-10 developed colitic-type dysplasia (P = .0001) or carcinoma (P = .0001) correlated with increasing inflammation. CONCLUSIONS: Breeding the Min +/- genotype into the IL-10 -/- background increased the incidence of colonic adenomas. Our studies demonstrate that acceleration of dysplasia and progression to invasion were associated with the degree of the inflammatory response in mice deficient in IL-10. These findings provide a novel system to dissect the pathways by which inflammatory mechanisms accelerate adenoma formation.

Prostate-specific antigen screening and prostate cancer treatment in renal transplantation candidates: A survey of U.S. transplantation centers.

INTRODUCTION: Renal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. MATERIALS AND METHODS: A 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent's institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. RESULTS: A total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. CONCLUSIONS: Although most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population.

The RAGE axis in early diabetic retinopathy.

PURPOSE: The receptor for advanced glycation end products (AGEs) has been implicated in the pathogenesis of diabetic complications. This study was conducted to characterize the role of the RAGE axis in a murine model of nonproliferative diabetic retinopathy (NPDR). METHODS: The retinas of hyperglycemic, hyperlipidemic (HGHL, apolipoprotein E(-/-) db/db) mice were examined for the development of early retinal vascular lesions of NPDR and compared to littermates at 6 months of age. Neural function was assessed with electroretinography. Immunohistochemistry, real-time RT-PCR, autofluorescence, and ELISA studies were used to localize and quantify the AGE/RAGE axis. Soluble RAGE, a competitor of cellular RAGE for its ligands, was administered to assess the impact of RAGE blockade. RESULTS: Early inner retinal neuronal dysfunction, manifested by prolonged latencies of the oscillatory potentials and b-wave, was detected in hyperglycemic mice. HGHL mice exhibited accelerated development of acellular capillaries and pericyte ghosts compared with littermate control animals. AGEs were localized primarily to the vitreous cavity and internal limiting membrane (ILM) of the retina, where they were intimately associated with the footplates of RAGE-expressing Müller cells. AGE accumulation measured by ELISA was increased within the retinal extracellular matrix of hyperglycemic mice. AGE fluorescence and upregulation of RAGE transcripts was highest in the retinas of HGHL mice, and attenuation of the RAGE axis with soluble RAGE ameliorated neuronal dysfunction and reduced the development of capillary lesions in these mice. CONCLUSIONS: In early diabetic retinopathy, the RAGE axis, comprising the cellular receptor and its AGE ligands, is amplified within the retina and is accentuated along the vitreoretinal interface. Antagonism of the RAGE axis in NPDR reduces neurovascular perturbations, providing an important therapeutic target for intervention.

Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.

BACKGROUND: The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion. METHODS: Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured. RESULTS: Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives. CONCLUSIONS: Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.

Validation of mean arterial pressure as an indicator of acute changes in cardiac output.

Changes in mean arterial pressure (MAP) are often assumed to reflect changes in cardiac output (CO). A linear relationship is postulated to exist between these two quantities based upon the circuit model for systemic circulation. Previous studies have correlated changes in CO and MAP. However, to our knowledge, no studies have tested the relationship between CO and MAP in vivo without changes in systemic vascular resistance. Research on baroreceptor stimulation and vasomotor response has shown that vasomotor tone changes 15 to 60 seconds after an acute change in CO. Maximal activation of vasomotor response occurs after approximately 30 seconds. Thus MAP should correlate directly with CO during acute changes (< 15 seconds). To test this, we examined the relationship between CO and MAP during 10 second occlusions of the inferior vena cava in anesthetized pigs. A linear relationship existed between CO and MAP in seven pigs (%MAP = 0.60[%CO] - 0.41, p = 0.0001). This study validates the use of MAP as an indicator of acute changes in CO. Fluctuations in MAP correlate well with acute changes in CO in the absence of changes in vascular tone.

Positive perceptions on safety and satisfaction during a patient-centered timeout before peripheral nerve blockade.

OBJECTIVES: To determine the psychometric outcomes of patients participating in an extensive patient-centered verification process before receiving sedation for regional anesthesia. DESIGN: Survey. SETTING: Perioperative areas of university-affiliated hospital. PATIENTS: Two hundred eligible patients scheduled for elective orthopedic surgery undergoing peripheral nerve blockade. INTERVENTIONS: Postoperative survey evaluating patient perception, experience, and satisfaction with the anesthetic timeout before regional anesthesia. MEASUREMENTS: Measures using numeric rating scales were obtained on patient perceptions of safety, confidence in anesthesia provider, anxiety, and positive sentiments during participation in block timeout. These variables were analyzed using logistic regression models to correlate with reported pain and satisfaction perioperatively. MAIN RESULTS: One hundred seventy-five patients (93% enrollment) completed the study. More than 90% of patients reported agreeing strongly to feeling safe, confident, relaxed, and positive about their participation in the block timeout. These sentiments are associated with less reported perioperative pain and higher overall satisfaction. CONCLUSIONS: Patient perceptions of confidence and safety in regional anesthesia providers were enhanced by a preprocedural timeout process. These positive attitudes are associated with a superior perioperative experience and patient satisfaction.