Prospective Randomized Trial of Maintenance Immunosuppression With Rapid Discontinuation of Prednisone in Adult Kidney Transplantation

Rapid discontinuation of prednisone (RDP) has minimized steroid‐related complications following kidney transplant (KT). This trial compares long‐term (10‐year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high‐level tacrolimus (TAC, 8–12 μg/L) and low‐level sirolimus (SIR, 3–7 μg/L) (TAC^H/SIR^L, n = 149) or low‐level TAC (3–7 μg/L) and high‐level SIR (8–12 μg/L) (TAC^L/SIR^H, n = 140). Median follow‐up was ～7 years. There were no differences between arms in 10‐year actuarial patient, graft and death‐censored graft survival or in allograft function. There were no differences in the 10‐year actuarial rates of biopsy‐proven acute rejection (30%, 26% and 20% in CSA/MMF, TAC^H/SIR^L and TAC^L/SIR^H) and chronic rejection (38%, 35% and 31% in CSA/MMF, TAC^H/SIR^L and TAC^L/SIR^H). Rates of new‐onset diabetes mellitus were higher with TAC^H/SIR^L (p = 0.04), and rates of anemia were higher with TAC^H/SIR^L and TAC^L/SIR^H (p = 0.04). No differences were found in the overall rates of 16 other post‐KT complications. These data indicate that RDP‐based protocol yield acceptable 10‐year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.     

A Composite Risk Model for Predicting Technical Failure in Pancreas Transplantation

Technical failure (TF) continues to have a significant impact on the success of pancreas transplantation. We assessed risk factors for TF in 1115 pancreas transplants performed at a single center between 1998 and 2011. The overall TF rate was 10.2%. In a multivariable model, donor BMI ≥30 (HR 1.87, p = 0.005), donor Cr ≥2.5 (HR 3.16, p = 0.007), donor age >50 (HR 1.73, p = 0.082) and preservation time >20 h (HR 2.17, p < 0.001) were associated with TF. Bladder drainage of exocrine secretions was protective (HR 0.54, p = 0.002). We incorporated these factors in a Composite Risk Model. In this model the presence of one risk factor did not significantly increase risk of TF (HR 1.35, p = 0.346). Two risk factors in combination increased risk greater than threefold (HR 3.65, p < 0.001) and three risk factors increased risk greater than sevenfold (HR 7.66, p = <0.001). The analysis also identified many factors that were not predictive of TF, including previous transplants, immunosuppressive agent selection, and almost all recipient demographic parameters. While the model suggests that two or more risk factors predict TF, strategies to reduce preservation time may mitigate some of this risk.     

Patient and Provider-Identified Factors Contributing to Surgical Readmission After Colorectal Surgery

Purpose: Nearly one in seven surgical patients is readmitted to the hospital within 30 days of discharge. Few studies have identified patient-centric factors that raise the risk of both preventable and nonpreventable postoperative readmissions. Materials and Methods: Over 6 months in 2012, 48 colorectal surgical patients were identified on re-admission within 30 days of discharge. We prospectively obtained information on the patient's and primary surgeon's views on factors that contributed to readmission, and compiled data to produce an external list of contributing factors. A standard cost analysis was performed. Results: 48 colorectal surgery patients participated, and 47 were included in this patient-centric evaluation of factors leading to readmission. The three primary readmission diagnoses included dehydration, fever, and ileus or small bowel obstruction. Of all readmissions, 23% were considered to be preventable. 38% of patients had scheduled follow-up appointments that were documented in the medical record at the time of discharge. Providers identified several factors contributing to readmission including difficulty understanding discharge plan, medication management and premature discharge. Per patient, the cost of preventable readmission was $15,366 (±20%; $12,293–$18,439). Total preventable cost was $169,025 (±20%; $135,220–$202,829). Conclusions: The ability to obtain an outpatient postoperative appointment and the understanding of their own postoperative care were the most commonly identified barriers. Interventions to help reduce unnecessary readmissions include a standard discharge process and coordinator, and routine (<7 days) postdischarge outpatient appointments. Successful reduction of preventable readmissions would result in approximately $3.6 million in cost savings per 1,000 colorectal readmissions.     

Quantification of diphtheria toxin mediated ADP-ribosylation in a solid-phase assay

BACKGROUND: Because of reduced vaccination programs, the number of diphtheria infections has increased in the last decade. Diphtheria toxin (DT) is expressed by Corynebacterium diphtheriae and is responsible for the lethality of diphtheria. DT inhibits cellular protein synthesis by ADP-ribosylation of the eukaryotic elongation factor 2 (eEF2). No in vitro system for the quantification of DT enzymatic activity exists. We developed a solid-phase assay for the specific detection of ADP-ribosylation by DT. METHODS: Solid phase-bound his-tag eEF2 is ADP-ribosylated by toxins using biotinylated NAD(+) as substrate, and the transferred biotinylated ADP-ribose is detected by streptavidin-peroxidase. DT enzymatic activity correlated with absorbance. We measured the amount of ADP-ribosylated eEF2 after precipitation with streptavidin-Sepharose. Quantification was done after Western blotting and detection with anti-his-tag antibody using an LAS-1000 System. RESULTS: The assay detected enzymatically active DT at 30 ng/L, equivalent to 5 mU/L ADP-ribosylating activity. Pseudomonas exotoxin A (PE) activity was also detected at 100 ng/L. We verified the assay with chimeric toxins composed of the catalytic domain of DT or PE and a tumor-specific ligand. These chimeric toxins revealed increased signals at 1000 ng/L. Heat-inactivated DT and cholera toxin that ADP-ribosylates G-proteins did not show any signal increase. CONCLUSIONS: The assay may be the basis for the development of a routine diagnostic assay for the detection of DT activity and highly specific inhibitors of DT.     

Assessment of colour doppler tissue imaging using test-phantoms

An investigation has been carried out on the velocity resolution, spatial resolution and accuracy of Doppler images as part of a study into the Doppler display of cardiac tissue motion. Test-phantoms were designed to perform this work and images were captured on a computer. The characteristics of the phantom images and of the image capture process were studied. The smallest spatial detail that was observed in the Doppler image was 3 mm by 3 mm. Doppler receive gain and Doppler ensemble size both affected velocity resolution. Different target materials gave different measures for velocity resolution. This could be related to the different back-scatter intensities of the materials.     

Use of preoperative antidepressants is not associated with postoperative hospital length of stay

Purpose

Antidepressant medications are commonly prescribed for the treatment of depression, anxiety, and chronic pain. Their use may lead to a number of side effects with important implications in the perioperative period. Our aim was to examine the effect of preoperative antidepressant administration on post-surgical hospital length of stay (LOS) in elective non-cardiac surgery patients.

Design

Historical cohort study.

Methods

Demographic and preoperative data were collected by chart review for all non-cardiac surgery patients who were assessed in the preoperative consult clinic from April 2008 through February 2009. Patients were grouped according to whether or not they were taking antidepressant medications. Median length of stay was compared between patients who took antidepressants preoperatively and those who did not.

Results

Data were collected for 3,692 patients. Two hundred eighty-nine (7.8%) patients were taking antidepressants preoperatively. Use of antidepressants was not associated with an increased hospital LOS. The median LOS was four days both for patients who took antidepressants preoperatively (95% confidence interval [CI] 4 to 4) and for those who did not (95% CI 3 to 5) (P = 0.13).

Conclusions

The preoperative use of antidepressant medications was not associated with increased postoperative hospital LOS following elective non-cardiac surgery.     

A cross-sectional study of knife injuries at a London major trauma centre

INTRODUCTION

No national recording systems for knife injuries exist in the UK. Understanding the true size and nature of the problem of knife injuries is the first stage in reducing the burden of this injury. The aim of this study was to survey every knife injury seen in a single inner city emergency department (ED) over a one-year period.

METHODS

A cross-sectional observational study was performed of all patients attending with a knife injury to the ED of a London major trauma centre in 2011. Demographic characteristics, patterns of injury, morbidity and mortality data were collected.

RESULTS

A total of 938 knife injuries were identified from 127,191 attendances (0.77% of all visits) with a case fatality rate of 0.53%. A quarter (24%) of the major trauma team’s caseload was for knife injuries. Overall, 44% of injuries were selfreported as assaults, 49% as accidents and 8% as deliberate self-harm. The highest age specific incident rate occurred in the 16–24 year age category (263/100,000). Multiple injuries were seen in 19% of cases, of which only 81% were recorded as assaults. The mean length of stay for those admitted to hospital was 3.04 days. Intrathoracic injury was seen in 26% of cases of chest trauma and 24% of abdominal injuries had a second additional chest injury.

CONCLUSIONS

Violent intentional injuries are a significant contributory factor to the workload of the major trauma team at this centre. This paper contributes to a more comprehensive understanding of the nature of these injuries seen in the ED.