The Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplant

Background and objectives

There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted.

Design, setting, participants, & measurements

In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%).

Results

The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R²) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients.

Conclusions

Routine use of biopsies could lead to unnecessary kidney discards.     

The impact of elevated serum IgG4 levels in patients with primary sclerosing cholangitis

Background

Elevated IgG4 levels have been reported among patients with primary sclerosing cholangitis. Epidemiological data has only been provided from tertiary centres.

Aims

To investigate the prevalence of elevated IgG4 levels and to compare prognosis between patients with and without elevated IgG4 levels in serum in two European cohorts of patients with primary sclerosing cholangitis.

Methods

Serum IgG4-levels were measured in a consecutive series of patients from Berlin, and retrospectively collected in a population-based cohort from Sweden (total N = 345). Cox's proportional hazard analysis was used to calculate relative risks for liver-related death or liver transplantation and cholangiocarcinoma.

Results

Elevated IgG4 values were demonstrated in 10% of patients. A previous history of pancreatitis, combined intra- and extrahepatic biliary involvement and jaundice were independently associated with elevated IgG4 in multivariate analysis. IgG4 status was not associated with an increased risk for the combined endpoint liver-related death or liver transplantation or cholangiocarcinoma.

Conclusion

The prevalence of elevated IgG4 values among European patients with primary sclerosing cholangitis is similar to what previously has been reported from the United States. Elevated IgG4 was not associated with an increased risk of liver transplantation or liver-related death or cholangiocarcinoma.     

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.     

First Clinical Experience with Intranasal Cooling for Hyperthermia in Brain-Injured Patients

Introduction

Hyperthermia is common in brain-injured patients and associated with a worse outcome. As brain rather than body temperature reduction, theoretically, is the most important in cerebral protection, there is logic in targeting cooling at the brain. Selective brain cooling can, in theory, be obtained by cooling the skull or by heat loss from the upper airways. In this preliminary safety and efficacy study, we report clinical data from brain-injured patients who because of hyperthermia were treated with intranasal cooling.

Methods

Nine intubated brain-injured patients with hyperthermia were treated using a prototype intranasal balloon system perfused with cold saline. Temperature in the cerebrum, esophagus, and bladder was monitored together with intracranial pressure.

Results

In only two of nine patients, normothermia was reached in the esophagus and in only four of nine patients it was reached in the bladder. When normothermia was reached, the time to normothermia was delayed. In the brain, normothermia was reached in two of five patients after approximately 72 h. Median temperature curves from the first 72 h of cooling showed that normothermia was not reached in any of the three compartments. The temperature in the brain and bladder were on average 0.6 and 0.5 °C higher than in the esophagus. ICP increased with increasing brain temperature. We found no signs of clinical important injury to the nasal mucosa from the cold saline or pressure in the balloons.

Conclusion

In brain-injured patients with hyperthermia, cooling with a prototype intranasal balloon system was clinically inadequate as the effect was delayed and not brain selective.     

Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events

Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS⁺) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S′ allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S′ allele with a history of SLEs demonstrated elevated reactivity to the CS⁺ in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.     

Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS

BackgroundHyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction.Methods and ResultsA total of 6,496 patients from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5–5.5 mmol/L (normoglycemia), 5.5–8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06–1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27–1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes.ConclusionsIn heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.     

MicroRNA expression profiling of carcinoma in situ cells of the testis

Testicular germ cell tumours, seminoma (SE) and non-seminoma (NS), of young adult men develop from a precursor cell, carcinoma in situ (CIS), which resembles foetal gonocytes and retains embryonic pluripotency. We used microarrays to analyse microRNA (miRNA) expression in 12 human testis samples with CIS cells and compared it with miRNA expression profiles of normal adult testis, testis with Sertoli-cell-only that lacks germ cells, testis tumours (SE and embryonal carcinoma (EC), an undifferentiated component of NS) and foetal male and female gonads. Principal components analysis revealed distinct miRNA expression profiles characteristic for each of the different tissue types. We identified several miRNAs that were unique to testis with CIS cells, foetal gonads and testis tumours. These included miRNAs from the hsa-miR-371-373 and -302-367 clusters that have previously been reported in germ cell tumours and three miRNAs (hsa-miR-96, -141 and -200c) that were also expressed in human epididymis. We found several miRNAs that were upregulated in testis tumours: hsa-miR-9, -105 and -182-183-96 clusters were highly expressed in SE, while the hsa-miR-515-526 cluster was high in EC. We conclude that the miRNA expression profile changes during testis development and that the miRNA profile of adult testis with CIS cells shares characteristic similarities with the expression in foetal gonocytes.     

Influence of peritoneal dialysis solution on measurements of fluid status by bioimpedance spectroscopy

Purpose and methods

The accurate estimation of volume status is a central problem in dialysis patients. Recently, a bioimpedance spectroscopy (BIS) device (BCM Body Composition Monitor FMC, Germany) has attained growing interest in this regard. By processing the raw data for extracellular water (ECW) and intracellular water (ICW) by means of a validated body composition model, this device allows a quantification of the individual fluid overload (FO) compared to a representative healthy population. In this study, we addressed the issue whether the presence of peritoneal dialysate has an impact on measurements of FO by BIS in PD patients.

Results

Forty-two BIS measurements using the BCM device were performed both in the absence (D?) and presence (D+) of peritoneal dialysate in 17 stable PD patients. Data for ECW, ICW and FO (D+; D?) were analyzed by paired t test and linear regression. Mean FO was 0.99 ± 1.17 L in D? and 0.94 ± 1.27 in D+ (p = n.s. paired t test). Linear regression demonstrated an excellent degree of conformity between FO (D?) and FO (D+) (r ² = 0.93).

Conclusion

The presence of peritoneal fluid in PD patients has a negligible influence on measurements of FO by BIS. The BIS measurements can be therefore conveniently and reliably done without emptying the peritoneal cavity; this may facilitate the use of BIS in this particular group of patients.