Development of a Microsphere-Based Immunoassay Authenticating A2 Milk and Species Purity in the Milk Production Chain.

Processed milk and milk products produced from bovine milk, commonly contain ß-casein A1 (ßCA1) and ß-casein A2 (ßCA2). Since the presence of ßCA1 is linked to milk intolerance and digestion problems, A2A2 milk, which only contains ßCA2, is proposed as a healthier alternative. To support this health claim, the purity of A2A2-milk has to be guaranteed. In the presented study, a multiplex immunoassay, able to distinguish between ßCA2 and ßCA1, was developed and real-life applicability was shown on raw milk samples from genotyped A1A1, A1A2 and A2A2 cows. Because of its ability to discriminate between ßCA2 and ßCA1, this newly developed method was able to detect the addition of common bovine A1A2 milk to A2A2 milk, as low as 1%. Besides the detection of A2A2 milk purity, the developed assay can also be implemented as a rapid phenotyping method at dairy farms to replace the more invasive DNA-based screening. Additionally, the developed method was capable of detecting the addition of common bovine milk up to 1% in sheep, goat, buffalo, horse and donkey milk, which conforms to EU recommendations. In conclusion, a newly developed multiplex method capable of reliably detecting the dilution of A2A2 milk of multiple species, with common bovine milk up to 1%, is presented.

Addressing morbid obesity as a barrier to renal transplantation with laparoscopic sleeve gastrectomy.

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25-month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m(2) (range 35.8-67.7 kg/m(2)). Follow-up after LSG was 220 ± 152 days (range 26-733 days) with last BMI of 36.3 ± 5.3 kg/m(2) (range 29.2-49.8 kg/m(2)) with 29 (55.8%) patients achieving goal BMI of <35 kg/m(2) at 92 ± 92 days (range 13-420 days). The mean percentage of excess weight loss (%EWL) was 32.1 ± 17.6% (range 6.7-93.8%). A segmented regression model was used to compare medical therapy versus LSG. This revealed a statistically significant increase in the BMI reduction rate (0.3 kg/m(2)/month versus 1.1 kg/m(2)/month, p < 0.0001). Patients also experienced a 40.9% decrease in anti-hypertensive medications (p < 0.001) and a 49.7% decrease in total daily insulin dose (p < 0.001). LSG is a safe and effective means for addressing obesity in kidney transplant candidates in the context of a multidisciplinary approach.

Estimating Surgical Urethral Length on Intraoperative Robot-Assisted Prostatectomy Images Using Artificial Intelligence Anatomy Recognition.

Objective: To construct a convolutional neural network (CNN) model that can recognize and delineate anatomic structures on intraoperative video frames of robot-assisted radical prostatectomy (RARP) and to use these annotations to predict the surgical urethral length (SUL). Background: Urethral dissection during RARP impacts patient urinary incontinence (UI) outcomes, and requires extensive training. Large differences exist between incontinence outcomes of different urologists and hospitals. Also, surgeon experience and education are critical toward optimal outcomes. Therefore, new approaches are warranted. SUL is associated with UI. Artificial intelligence (AI) surgical image segmentation using a CNN could automate SUL estimation and contribute toward future AI-assisted RARP and surgeon guidance. Methods: Eighty-eight intraoperative RARP videos between June 2009 and September 2014 were collected from a single center. Two hundred sixty-four frames were annotated according to prostate, urethra, ligated plexus, and catheter. Thirty annotated images from different RARP videos were used as a test data set. The dice (similarity) coefficient (DSC) and 95th percentile Hausdorff distance (Hd95) were used to determine model performance. SUL was calculated using the catheter as a reference. Results: The DSC of the best performing model were 0.735 and 0.755 for the catheter and urethra classes, respectively, with a Hd95 of 29.27 and 72.62, respectively. The model performed moderately on the ligated plexus and prostate. The predicted SUL showed a mean difference of 0.64 to 1.86 mm difference vs human annotators, but with significant deviation (standard deviation = 3.28-3.56). Conclusion: This study shows that an AI image segmentation model can predict vital structures during RARP urethral dissection with moderate to fair accuracy. SUL estimation derived from it showed large deviations and outliers when compared with human annotators, but with a small mean difference (<2 mm). This is a promising development for further research on AI-assisted RARP.

Fast and Accurate Ophthalmic Medication Bottle Identification Using Deep Learning on a Smartphone Device.

PURPOSE: To assess the accuracy and efficacy of deep learning models, specifically convolutional neural networks (CNNs), to identify glaucoma medication bottles. DESIGN: Algorithm development for predicting ophthalmic medication bottles using a large mobile image-based dataset. PARTICIPANTS: A total of 3750 mobile images of 5 ophthalmic medication bottles were included: brimonidine tartrate, dorzolamide-timolol, latanoprost, prednisolone acetate, and moxifloxacin. METHODS: Seven CNN models were initially pretrained on a large-scale image database and subsequently retrained to classify 5 commonly prescribed topical ophthalmic medications using a training dataset of 2250 mobile-phone captured images. The retrained CNN models' accuracies were compared using k-fold cross-validation (k = 10). The top 2 performing CNN models were then embedded into separate iOS apps and evaluated using 1500 mobile images not included in the training dataset. MAIN OUTCOME MEASURES: Prediction accuracy, image processing time. RESULTS: Of the 7 CNN architectures, MobileNet v2 yielded the highest k-fold cross-validation accuracy of 0.974 (95% confidence interval [CI], 0.966-0.980) and the shortest average image processing time at 3.45 (95% CI, 3.13-3.77) sec/image. ResNet V2 had the second highest accuracy of 0.961 (95% CI, 0.952-0.969). When the 2 app-embedded CNNs were compared, in terms of accuracy, MobileNet V2, with an image prediction accuracy of 0.86 (95% CI, 0.84-0.88), was significantly greater than ResNet V2, 0.68 (95% CI, 0.66-0.71) (Table 1). Sensitivities and specificities varied between medications (Table 1). There was no significant difference in average imaging processing time, 0.32 (95% CI, 0.28-0.36) sec/image and 0.31 (95% CI, 0.29-0.33) sec/image for MobileNet V2 and ResNet V2, respectively. Information on beta-testing of the iOS app can be found here: https://lin.hs.uci.edu/research/. CONCLUSIONS: We have retrained MobileNet V2 to accurately identify ophthalmic medication bottles and demonstrated that this neural network can operate in a smartphone environment. This work serves as a proof-of-concept for the production of a CNN-based smartphone application to empower patients by decreasing risk for error.

The Relationship Between the Functional Gait Assessment and Quality-of-Life Data in Patients Undergoing Vestibular Schwannoma Resection.

OBJECTIVE: To examine the relationship between the Functional Gait Assessment (FGA) and quality of life (QOL) measurements relating to balance before and after vestibular schwannoma (VS) resection and to assess the role of preoperative FGA in predicting postoperative QOL. STUDY DESIGN: A prospective clinical study of adult patients undergoing VS resection between September 2018 and December 2019. FGA was administered 1 week before and after surgery. Dizziness Handicap Inventory (DHI) and Penn Acoustic Neuroma Quality of Life (PANQOL) were administered preoperatively and at 3 months postoperatively. SETTING: Single tertiary center. PATIENTS: Patients (age ≥ 18 years old) with VS undergoing microsurgical resection. Excluded were patient with previous surgery or radiation. INTERVENTION: VS resection. MAIN OUTCOMES AND MEASURES: Primary outcome: correlation between FGA and QOL surveys. Secondary outcome: correlation between preoperative measurements of balance and postoperative PANQOL. RESULTS: One hundred thirty-eight patients were analyzed (mean age: 48 years old, 65.9% female). The translabyrinthine approach was most commonly performed. Under multivariate analysis, preoperative FGA significantly correlated with preoperative PANQOL balance score (p < 0.0001), preoperative PANQOL total score (p = 0.0002), and preoperative DHI (p < 0.0001). However, postoperative FGA did not significantly correlate with postoperative PANQOL balance or total scores (p = 0.446 and p = 0.4, respectively), or postoperative DHI (p = 0.3). Univariate analysis demonstrated that preoperative DHI and preoperative FGA were predictive of changes in postoperative PANQOL balance and total scores. However under multivariate analysis, preoperative FGA did not predict changes in postoperative PANQOL balance or total score (p = 0.24; p = 0.28, respectively). Preoperative DHI remained predictive of changes in postoperative PANQOL balance (p = 0.03) score but not of postoperative PANQOL total score (p = 0.37). CONCLUSIONS: Although FGA and QOL data significantly correlated in the preoperative setting, our results did not suggest that preoperative FGA can be used to determine postoperative QOL. Additionally, the lack of correlation between FGA and QOL measurements in the acute postoperative setting suggests that further research is needed to determine contributors to postoperative QOL.

Identifying the relationship between postoperative urinary continence and residual urethra stump measurements in robot assisted radical prostatectomy patients.

OBJECTIVE: To investigate the feasibility of urethral stump length and width measurements in recorded videos of robot assisted radical prostatectomy procedures using the Kinovea software and to assess if these measurements could be used as predictors of postoperative urinary continence. METHODS: Fifty-three patients were selected from an institutional database of 1400 cases and included in the study. All videos were analysed using the computer software 'Kinovea'. All measurements were performed using the inserted bladder catheter as a reference point. RESULTS: The reference point (bladder catheter) was available in 33 out of 53 patients. The median surgical urethral length (SUL) was significantly higher in the continent group (1050 vs. 1294 mm, p = 0.018). The urethral width measurements did not show a difference between the groups. In order to validate the Kinovea software as an accurate tool for the measurement of the urethral stump length and width results were correlated with the magnetic resonance imaging measurements of the urethra. CONCLUSIONS: The results of this study showed a significantly longer median SUL incontinent patients.

Taiwanese nurses' cognition and attitudes towards the Magnet Hospitals Recognition Programme.

AIMS: To explore the relevance and feasibility of using the Magnet Recognition Programme (MRP) at a Taiwanese hospital. BACKGROUND: Since no hospitals in Taiwan have applied for American Nurses Credentialing Center Magnet Recognition, and the American medical system and customs are different from those in Taiwan, this study explores whether or not the MRP is appropriate for Taiwanese hospitals. METHOD: This study used a cross-sectional design with data collected from 905 nurses at a 1200-bed Taiwanese military hospital. The authors created the structured questionnaire from a framework based on the 14 Forces of Magnetism. The study used descriptive and inferential statistical analyses to explain the nurses' cognitions and attitudes towards the MRP and to discover if variations in these concepts occurred across nurses' demographics and their job classification. FINDINGS: The mean nurses' cognitive score on each item varies from 3.3 to 4.1, and the mean nurses' attitude score on each item varies from 3.0 to 4.0 (both with the highest possible score related to the 14 Forces of Magnetism being 5.0). Using regression analysis, overall cognitive score, working in the operating room, or the sub-critical Neonatal Care Unit, and part-time hours of work explained 42% of the variance in the total attitude score towards the MRP. CONCLUSION: The findings indicate that when nurses have a higher cognition towards MRP, the more positive are their attitudes towards seeking the MRP. Using these findings and information about the nurses, the authors suggest strategies that hospital executives and nursing supervisors can use to improve nurses' cognition and attitudes when preparing to seek recognition through the MRP.

A Prospective, Observational, Multicentre Study Concerning Nontechnical Skills in Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy.

INTRODUCTION AND HYPOTHESES: valuation of surgical skills, both technical and nontechnical, is possible through observations and video analysis. Besides technical failures, adverse outcomes in surgery can also be related to hampered communication, moderate teamwork, lack of leadership, and loss of situational awareness. Even though some surgeons are convinced about nontechnical skills being an important part of their professionalisation, there is paucity of data about a possible relationship between nontechnical skills and surgical outcome. In robot-assisted surgery, the surgeon sits behind the console and is at a remote position from the surgical field and team, making communication more important than in open surgery and conventional laparoscopy. A lack of structured research makes it difficult to assess the value of the different analysis methods for nontechnical skills, particularly in robot-assisted surgery. Our hypothesis includes the following: (1) introduction of robot-assisted surgery leads to an initial decay in nontechnical skills behaviour during the learning curve of the team, (2) nontechnical skills behaviour is more explicitly expressed in experienced robot-assisted surgery teams than in experienced open surgery teams, and (3) introduction of robot-assisted surgery leads to the development of different forms of nontechnical skills behaviour compared with open surgery. DESIGN: This study is a prospective, observational, multicentre, nonrandomised, case-control study including bladder cancer patients undergoing either an open radical cystectomy or a robot-assisted radical cystectomy at the Catharina Hospital Eindhoven, the Netherlands, or at the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam. All patients are eligible for inclusion; there are no exclusion criteria. The Catharina Hospital Eindhoven, the Netherlands, performs on average 35 radical cystectomies a year. The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital Amsterdam, performs on average 100 radical cystectomies a year. PROTOCOL OVERVIEW: The choice of treatment is at the discretion of the patient and the surgeon. Patient results will be obtained prospectively. Pathology results as well as complications occurring within 90 d following surgery will be registered. Surgical complications will be registered according to the Clavien-Dindo system. MEASUREMENTS: Nontechnical skills will be observed using five different methods: (1) NOTSS: Nontechnical Skills for Surgeons; (2) Oxford NOTECHS II: a modified theatre team nontechnical skills scoring system; (3) OTAS: Observational Teamwork Assessment for Surgery; (4) Interpersonal and Cognitive Assessment for Robotic Surgery (ICARS): evaluation of nontechnical skills in robotic surgery; and (5) analysis of human factors. Technical skills in robot-assisted radical cystectomy will be analysed using two different methods: (1) GEARS: Global Evaluative Assessment of Robotic Skill and (2) GERT: Generic Error Rating Tool. SAFETY CRITERIA AND REPORTING: Formal ethical approval has been provided by Medical research Ethics Committees United (MEC-U), The Netherlands (reference number W19.048). We hope to present the results of this study to the scientific community at conferences and in peer-reviewed journals. STATISTICAL ANALYSIS: Frequency statistics will be calculated for patient demographical data, and a Shapiro-Wilk test with p > 0.05 will be used to define normal distribution. Univariate analysis will be conducted to test for statistically significant differences in observation scores between open radical cystectomy and robot-assisted radical cystectomy cohorts across all variables, using independent sample t tests and Mann-Whitney U testing, as appropriate. A variable-selection strategy will be used to create multivariate models. Binary logistic regression will be conducted to calculate odds ratios and 95% confidence intervals for significant predictors on univariate analysis and clinically relevant covariates. Statistical significance is set at p < 0.05 based on a two-tailed comparison. SUMMARY: This study uses a structured approach to the analysis of nontechnical skills using extracorporeal videos of both open radical cystectomy and robot-assisted radical cystectomy surgeries, in order to obtain detailed data on nontechnical skills during open and minimally invasive surgeries. The results of this study could possibly be used to develop team-training programmes, specifically for the introduction of the surgical robot in relation to changes in nontechnical skills. Additional analysis of technical skills using the intracorporeal footage of the surgical robot will be used to elucidate the role of surgical skills and surgical events in nontechnical skills.

Analysis of the video motion tracking system "Kinovea" to assess surgical movements during robot-assisted radical prostatectomy.

BACKGROUNDS: Robot-assisted surgery facilitated the possibility to evaluate the surgeon's skills by recording and evaluating the robot surgical images. The aim of this study was to investigate the possibility of using a computer programme (Kinovea) for objective assessment of surgical movements in previously recorded in existing robot-assisted radical prostatectomy (RARP) videos. METHODS: Twelve entire RARP procedures were analysed by a trained researcher using the computer programme "Kinovea" to perform semi-automated assessment of surgical movements. RESULTS: Data analysis showed Kinovea was on average able to automatically assess only 22% of the total surgical duration per video of the robot-assisted surgery. On average, it lasted 4 hours of continued monitoring by the researcher to assess one RARP using Kinovea. CONCLUSION: Although we proved it is technically possible to use the Kinovea system in retrospective analysis of surgical movement in robot-assisted surgery, the acquired data do not give a comprehensive enough analysis of the video to be used in skills assessment.

High-precision Bladder Cancer Irradiation in the Elderly: Clinical Results for a Plan-of-the-day Integrated Boost Technique with Image Guidance Using Lipiodol Markers.

BACKGROUND: For most elderly patients with muscle-invasive bladder cancer (MIBC), surgery is not an option because of patient frailty. Conventional radiotherapy, with its high-dose irradiation of surrounding healthy tissues, remains the only curative treatment for this patient population. OBJECTIVE: To determine whether targeted radiotherapy with Lipiodol demarcation and plan-of-the-day integrated boost technique (LPOD) is a viable curative treatment for elderly patients with MIBC. DESIGN, SETTING, AND PARTICIPANTS: Between September 2008 and September 2016 all MIBC patients in our hospital were screened for eligibility. We included patients with localised, unifocal T2-T4N0M0 grade 2-3 MIBC. Patients with a tumour volume >50% of the bladder wall surface, previous pelvic radiotherapy, and unilateral or bilateral hip prostheses were excluded. INTERVENTION: Targeted radiotherapy using LPOD. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival, urothelial cell cancer-specific survival (UCCSS), disease recurrence, and Radiation Therapy Oncology Group (RTOG) toxicity were measured. Statistical analyses included independent-sample t tests, χ2 tests, and Mann-Whitney U tests. RESULTS AND LIMITATIONS: A total of 44 patients (median age 80 yr) were included. Over median follow-up of 38 mo, one patient ceased treatment and 23 patients died. LPOD resulted in a 11.4% chance of local recurrence, high 3-yr UCCSS of 77%, RTOG grade >3 toxicity of 2.3-12.9%, and 3-yr overall survival of 49%. CONCLUSIONS: LPOD is a feasible first-line treatment option for older patients with limited-volume T2-T4N0M0 grade 2-3 MIBC. PATIENT SUMMARY: We looked at outcomes after targeted radiotherapy in elderly patients with muscle-invasive bladder cancer. We found that this treatment results in a low chance of disease recurrence with few toxicity complaints. We conclude that this treatment is a viable first-line treatment option for elderly patients.

The value of a 1-day multidisciplinary robot surgery training for novice robot surgeons.

INTRODUCTION: To fulfil the need for a basic level of competence in robotic surgery (Brinkman et al., Surg Endosc Other Interv Tech 31(1):281-287, 2017; Dutch Health inspectorate (Inspectie voor de gezondheidszorg), Insufficient carefulness at the introduction of surgical robots (in Dutch: Onvoldoende zorgvuldigheid bij introductie van operatierobots), Igz, Utrecht, 2010), the NIVEL (Netherlands Institute for Healthcare Research) developed the 'Basic proficiency requirements for the safe use of robotic surgery' (BPR). Based on the BPR a 1-day robotic surgery training was organised to answer the following research questions: (1) Are novice robot surgeons able to accurately self-assess their knowledge and dexterity skills? (2) Is it possible to include the teaching of all BPRs in a 1-day training? MATERIALS AND METHODS: Based on the BPR, a robot surgery course was developed for residents and specialists (surgery, gynaecology and urology). In preparation, the participants completed an online e-module. The 1-day training consisted of a practical part on robot set-up, a theoretical section, and hands-on exercises on virtual reality robot simulators. Multiple online questionnaire was filled out by the participants at the end of the training to evaluate the perceived educational value of the course and to self-assess the degree to which BPRs were reached. RESULTS: 20 participants completed the training during the conference of the Dutch Association for Endoscopic Surgery (NVEC) in 2017. Participants indicated nearly all competency requirements were mastered at the end of the training. The competency requirements not mastered were, however, critical requirements for the safe use of the surgical robot. Skill simulation results show a majority of participants are unable to reach a proficient simulation score in basic skill simulation exercises. CONCLUSION: Results show novice robot surgeons are too positive in the self-assessment of their own dexterity skills after a 1-day training. Self-assessment revealed uncertainty of the obtained knowledge level on requirements for the safe use of the surgical robot. Basic courses on robotic training should inform trainees about their results to enhance learning and inform them of their competence levels.

Degradation of thymopentin by human lymphocytes: evidence for aminopeptidase activity.

Thymopentin (Arg-Lys-Asp-Val-Tyr) was shown to be degraded in vitro by human lymphocytes into two main fragments; the tetrapeptide Lys-Asp-Val-Tyr and the tripeptide Asp-Val-Tyr. Degradation products were identified by HPLC and amino-acid analysis. Analysis of the time-course of degradation revealed a 'stepwise' degradative event beginning at the N-terminal. The degradation of thymopentin after the first 10 min, as well as the formation of the tetrapeptide (5-30 min) were essentially curvilinear. Degradation of the tripeptide, was linear. Upon screening a panel of compounds that inhibit enzymatic activity, bestatin, amastatin and 1,10-phenanthroline were shown to be the most effective. Bestatin and amastatin caused an 85-90% inhibition of thymopentin degrading activity with IC50 values of 7.1 x 10(-6) M and 4.5 x 10(-9) M, respectively. 1,10-Phenanthroline completely inhibited the degradative process with an IC50 of 2 x 10(-4) M. When the tetrapeptide Lys-Asp-Val-Tyr was used as the starting substrate, similar IC50 values were seen for amastatin, bestatin and 1,10-phenanthroline. The importance of divalent metal ions in the degradative event was demonstrated not only by the effect of 1,10-phenanthroline, but also by the ability of Zn2+ and Co2+ to reverse the inhibition of 1,10-phenanthroline (at its IC50) to activities near control values (no inhibitor). These data strongly suggest that an aminopeptidase(s) is responsible for the degradative activity.

Neutral surface aminopeptidase activity of human tumor cell lines.

Seven human tumor cell lines were studied for their neutral surface aminopeptidase (AP) activity. The activity was shown to exist on all cell lines to varying degrees. The neutral AP activity of the cell lines had similar Km values and were affected by the same inhibitors as those reported for AP's of peripheral blood lymphocytes (PBL, Refs. 1 and 2). However, a difference was seen in the Vmax values of the various cell lines. These values were shown to correlate (r = 0.767, P less than 0.05) with cell surface area.

Neutrophils from burn patients are unable to increase the expression of CD11b/CD18 in response to inflammatory stimuli.

Neutrophils (PMNs) from patients with thermal injury are dysfunctional for the CD11b/CD18-dependent functions of diapedesis, chemotaxis, and phagocytosis. The expression of CD11b/CD18 on normal PMNs is increased after an inflammatory stimulus. We proposed that CD11b/CD18 expression on burn patient PMNs would respond abnormally to inflammatory stimuli. PMNs were obtained from nonseptic burn patients during the second week after thermal injury. PMNs from burn patients incubated with lipopolysaccharide (LPS), N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, or A23187 did not increase the expression of CD11b/CD18 to the same degree exhibited by normal PMNs. This inability to increase CD11b/CD18 was not due to differences in CD14 receptor expression, LPS binding, or factors present in the serum of burn patients. The upregulation of CD35 also was decreased on burn patient PMNs. Western blot analysis revealed decreased quantities of CD11b protein in burn patient PMNs compared with normal control PMNs. The deficiency in CD11b/CD18 expression after inflammatory stimuli may explain some of the abnormalities observed in burn PMN function.

Corticosteroid avoidance ameliorates lymphocele formation and wound healing complications associated with sirolimus therapy.

INTRODUCTION: Sirolimus (RAPA) and corticosteroids (CS) both inhibit wound healing. To evaluate the possibility that RAPA and CS have additive effects on wound healing, we evaluated the effects of corticosteroid avoidance (CSAV) on wound healing complications in patients treated with RAPA. METHODS: One hundred nine patients treated with a CSAV regimen (no pretransplantation or posttransplantation CS) were compared with a historical control group (n = 72) that received cyclosporine (CsA), mycophenolate mofetil (MMF), and CS. The CSAV group received low-dose CsA, MMF, RAPA, and thymoglobulin induction. Complications were classified as follows: wound healing complications (WHC) or infectious wound complications (IWC). WHC included lymphocele, hernia, dehiscence, diastasis, and skin edge separation. IWC included wound abscess and empiric antibiotic therapy for wound erythema. RESULTS: The CSAV group was largely CS-free: 11% of patients received CS for rejection, 12% of patients received CS for recurrent disease, and 85% of patients are currently off CS. The CSAV group had a significantly lower incidence of WHC (13.7% vs 28%; P = .03) and lymphoceles (5.5% vs 16%; P = .02) than the control group. There was no difference in the incidence of IWC between the 2 groups. Patients who received CSAV were 18% less likely (P = .57) to develop any type of complication, 41% less likely (P = .20) to develop a WHC, and 71% less likely (P = .018) to develop a lymphocele. CONCLUSIONS: CSAV in a RAPA-based regimen results in a marked reduction in WHC and lymphoceles. Therefore, CSAV provides a promising approach for addressing WHC associated with RAPA therapy.

Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.

UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.

Global cardiovascular risk under early corticosteroid cessation decreases progressively in the first year following renal transplantation.

UNLABELLED: A primary reason to eliminate corticosteroids from immunosuppressive regimens in solid organ transplant recipients is improved cardiovascular risk profiles. Although a number of studies have documented that corticosteroid withdrawal (CSWD) regimens reduce hypertension, hyperlipidemia, diabetes, and weight gain, global assessments of cardiovascular risk under CSWD have not been reported. The purpose of this study was to document cardiovascular risk under CSWD using a global risk assessment by Framingham risk assessment. METHODS: Framingham global cardiovascular risk assessments were performed at baseline and 3, 6, and 12 months posttransplant on patients enrolled in prospective, IRB-approved early (<7 days of corticosteroids) CSWD trials. Framingham score was based on age, sex, presence of diabetes, HDL and total cholesterol, and systolic blood pressure. All patients were nonsmokers. Left ventricular hypertrophy assessment by EKG criteria was not available at all time points and therefore were not included. RESULTS: One hundred eighty-three patients were included in the analysis. Fourteen percent of patients had evidence of coronary heart disease (prior MI, CABG, PTCA, or significant cardiovascular disease as evidenced by angiography) prior to transplant. Complete information was available for 160 patients at baseline, 132 at 1, 3, and 6 months, and 93 at 12 months posttransplant. Mean 10-year risk (expressed as percent) for developing coronary heart disease decreased over time: 8.03 at baseline, 8.31 at 3 months, 7.40 at 6 months, and 7.20 at 12 months, indicating that global cardiovascular risk fell at 1 year posttransplant by about 10% in renal transplant recipients undergoing early CSWD. CONCLUSIONS: Estimation of cardiovascular risk by Framingham risk factor assessment allows incorporation of several cardiovascular risk factors into a single estimate, thereby accounting for differential effects of each individual factor on global cardiovascular risk. This experience indicates that global cardiovascular risk decreases by approximately 10% at 1 year posttransplant in renal transplant recipients who undergo early corticosteroid withdrawal (CSWD).

A prospective, pilot study of early corticosteroid cessation in high-immunologic-risk patients: the Cincinnati experience.

BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein. METHODS: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1). CONCLUSIONS: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.

African American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African Americans have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. Modern immunosuppression has reduced rejections and improved graft survival in African Americans and may allow successful corticosteroid withdrawal. Outcomes in 56 African Americans were compared to 56 non-African Americans enrolled in early withdrawal protocols. Results are reported as African American versus non-African American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In conclusion, early withdrawal in African Americans is associated with acceptable rejection rates and excellent patient and graft survival, indicating that the risks and benefits of early withdrawal are similar between African Americans and non-African Americans. Additional followup is needed to determine long-term renal function, graft survival, and cardiovascular risk in African Americans with early steroid withdrawal.