Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets

BackgroundKidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury.MethodsA novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation.ResultsIn both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P < .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants.ConclusionProtection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.     

Psychometric validation of the Stoma-QOL questionnaire in a Canadian cross-sectional sample of colostomy and ileostomy patients

Objectives: The Stoma-QOL questionnaire is a patient-reported outcome (PRO) used to measure quality of life in patients with ileostomy or colostomy. This study assesses the Stoma-QOL’s overall and item-level psychometric characteristics in patients with temporary stomas, and whether stoma-related quality of life differs by demographic characteristics.

Materials and methods: Analysis of cross-sectional observational PRO data from hospitals in Vancouver, Canada. Patients registered for elective ileostomy or colostomy closure, over the age of 18, and able to read English were eligible for participation. Emergent and cancer-related cases were excluded. One-way analysis of variance was used to test for demographic differences in Stoma-QOL scores. Cronbach’s alpha was used for reliability, and Rasch item-response theory was used to assess overall and item characteristics.

Results: 120 patients were included. No statistically significant difference in Stoma-QOL scores was found by age, sex, or socioeconomic status. Reliability was 0.93. Mean item responses ranged from 1.77 to 3.55 and item-total correlation ranged from 0.51 to 0.77. The Rasch item-response theory model demonstrated significant misfit, likely due to the misfit of item 9, which asks about sexuality, and high residual correlations between item pairs 6 and 8 about fatigue, and items 16 and 17 about social relationships.

Conclusions: The Stoma-QOL questionnaire is a well-designed PRO for measuring stoma-related quality of life. Demographic variables do not appear to have a strong influence on Stoma-QOL scores. Item 9 demonstrated misfit but removal likely does not improve the instrument. Future research should focus on revising items 6, 8, 16, and 17.     

Liberal vs. conservative vasopressor use to maintain mean arterial blood pressure during resuscitation of septic shock: an observational study

OBJECTIVE: The optimal role of vasopressor therapy in septic shock is not known. We hypothesized that the variability in the use of vasopressors to treat hypotension is associated with subsequent organ failures. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care hospital. PATIENTS AND PARTICIPANTS: Consecutive patients with septic shock. MEASUREMENT AND RESULTS: Ninety-five patients were enrolled. Serial blood pressure recordings and vasopressor use were collected during the first 12h of septic shock. Median duration of hypotension that was not treated with vasopressors was 1.37h (interquartile range [IQR] 0.62-2.66). Based on the observed variability, we evaluated liberal (duration of untreated hypotension < median) vs. conservative (duration of untreated hypotensionn > median) vasopressor therapy. Compared with patients who received conservative vasopressor therapy, patients treated liberally had similar baseline organ impairment [median Sequential Organ Failure Assessment (SOFA) score 8 vs. 8, p = 0.438] were more likely to be younger (median age 70 vs. 77 years, p = 0.049), to require ventilator support (78 vs. 49%, p < 0.001), and to have progression of organ failures after 24h (59 vs. 37%, p = 0.032). When adjusted for age and mechanical ventilation, early therapy aimed at achieving global tissue perfusion [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.11-0.88), and early adequate antibiotic therapy (OR 0.27, 95% CI 0.09-0.76), but not liberal vasopressor use (OR 2.13, 95% CI 0.80-5.84), prevented progression of organ failures. CONCLUSIONS: In our retrospective study, early adequate antibiotics and achieving adequate global perfusion, but not liberal vasopressor therapy, were associated with improved organ failures after septic shock. Clinical trials which compare conservative vs. liberal vasopressor therapy are warranted.     

A decision-analysis model to diagnose feigned hand weakness

Malingering is a condition in which patients exaggerate incapacity. Feigned hand weakness is one form of malingering, and it is often seen after work-related hand injuries. Malingering is prevalent in the workers' compensation system, which devotes a large proportion of valuable resources to unwarranted claims. Feigned hand weakness must be detected early because it is relatively prevalent and expensive to society. Clinical evaluation is the first step in detecting feigned hand weakness, but it is not very specific. Therefore, every suspected positive clinical result must be followed up with a more advanced test that has better specificity. Three advanced tests are (1) five-rung grip test, (2) rapid grip tests (rapid exchange grip and rapid simultaneous grip), and (3) computerized measure of grip. Among these, computerized measure of grip is the most specific; therefore, it is the best second-line test.     

Significant elevations of serum lipase not caused by pancreatitis: a systematic review

Background

Many authors advocate lipase as the preferred serological test for the diagnosis of pancreatitis and a cut-off level of three or more times the upper limit of normal (ULN) is often quoted. The literature contains no systematic review that explores alternative causes of a lipase level over three times as high as the ULN. Such a review was therefore the objective of this study.

Methods

The EMBASE and MEDLINE databases (1985 to August 2013) were searched for all eligible articles. Predetermined data were extracted and independently analysed by two reviewers.

Results

In total, data from 58 studies were included in the final analysis. The following causes other than pancreatitis of lipase levels exceeding three times the ULN were found: reduced clearance of lipase caused by renal impairment or macrolipase formation; other hepatobiliary, gastroduodenal, intestinal and neoplastic causes; critical illness, including neurosurgical pathology; alternative pancreatic diagnoses, such as non-pathological pancreatic hyperenzymaemia, and miscellaneous causes such as diabetes, drugs and infections.

Conclusions

A series of differential diagnoses for significant serum lipase elevations (i.e. exceeding three times the ULN) has been provided by this study. Clinicians should utilize this knowledge in the interpretation and management of patients who have lipase levels over three times as high as the ULN, remaining vigilant for an alternative diagnosis to pancreatitis. The medical officer should be aware of the possibility of incorrect diagnosis in the asymptomatic patient.     

STAT-1-mediated repression of monocyte interleukin-10 gene expression in vivo

There have been substantial advances in understanding the events that regulate gene expression at the cellular and molecular level; however, there has been limited progress integrating this information to understand how biological systems function in vivo. For example, the anti-inflammatory cytokine IL-10 is thought to down-regulate the effects of the pro-inflammatory cytokine IFN-gamma on monocyte activation following LPS stimulation. However, the often-postulated reciprocal regulation of IL-10 gene expression by IFN-gamma has not been studied in vivo. Here we demonstrate that the regulation of IL-10 gene expression has at least two phases following challenge with LPS or a gram-negative organism. In C57BL/6 mice, early IL-10 induction occurs independently of STAT-1, while a delayed active repression of IL-10 gene expression is critically dependent on STAT-1, but only partially dependent upon IFN-alpha/beta and IFN-gamma. This in vivo IL-10 production comes from blood monocytes, but not tissue macrophages, and cannot be reproduced in vitro. This study provides new insights into the regulation of IL-10 following challenge with a gram-negative organism, and highlights the importance of studying these cytokine regulatory pathways in vivo.