A ‘Weight‐Listing’ Paradox for Candidates of Renal Transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.     

ES05ROUTINE PARAFIBROMIN IMMUNOHISTOCHEMISTRY OF LARGE PARATHYROID ADENOMAS IS NOT AN EFFECTIVE SCREENING STRATEGY FOR CARCINOMA

Purpose Parathyroid carcinoma (PC) is rare and accounts for less than 1% of all cases of primary hyperparathyroidism (PHPT). The definitive histopathologic diagnosis of PC requires unequivocal invasion or metastasis which may be absent at first presentation. As a result, many cases of PC can only be diagnosed retrospectively. Parafibromin is the protein encoded by HRPT2 which is mutated and not expressed in many parathyroid carcinomas. Given that PCs generally weigh more than parathyroid adenomas (PA)s, we hypothesized that amongst large PAs there may be a high incidence of occult PC which could be identified by negative staining for parafibromin. Methodology 57 parathyroid glands weighing greater than 2 grams excised from 1998–2006 were identified from the University of Sydney Endocrine Surgical Database. Two specimens with a histopathologic diagnosis of PC were excluded. Immunohistochemical staining for parafibromin was performed on the remaining 55 PAs. Results Of the 55 specimens stained for parafibromin only one definite negative stain was detected. This case was originally classified as an “atypical adenoma” because it showed nuclear and architectural atypia without unequivocal evidence of invasive growth. In view of the negative staining for parafibromin it therefore probably represents occult carcinoma. There has been no evidence of recurrence or metastasis after 6.5 years. Conclusions Complete loss of staining for parafibromin is very rare in giant parathyroid adenomas suggesting that occult carcinoma is equally rare. As a result routine immunohistochemical staining for parafibromin does not appear to be an effective screening test for carcinoma in large PA without histopathologic features of PC.     

Immunoadsorption in Severe C4d-Positive Acute Kidney Allograft Rejection: A Randomized Controlled Trial

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.     

Long-term outcomes evaluation after pars defect repair in adult low-grade isthmic spondylolithesis

Adult low-grade isthmic spondylolisthesis is often treated by posterolateral lumbar fusion (PLF), with a certain rate of complications and non-return to work. Alternatives to fusion, like pars defect repair (PDR), were used with encouraging results in young populations and athletes but their outcomes were rarely evaluated for adult patients. This retrospective study quantitatively analysed the long-term outcomes in adult isthmic spondylolisthesis patients treated by PLF or PDR. At a mean follow-up of 9 years, clinical, socio-professional, radiological data and Stauffer-Coventry score were available for 59 patients (39 cases treated by PLF and 20 treated by PDR). The overall clinical outcomes were comparable in both populations (88% in the PDR and 80% in PLF group 1), with a larger proportion of excellent results (56% vs. 10%) and of return to work in the PDR group. Radiological quantitative analysis highlighted stationary evolution and comparable outcomes for the two groups, except for vertebral slip evolution and adjacent level degeneration rate. Abnormal kinematic patterns outlined for PLF patients 20% of pseudarthrosis and 42% of adjacent levels hypermobility and for PDR ones low mobility for the levels adjacent to instrumented vertebra in 40% of cases. Quantified analysis of biomechanical parameters interpreted altogether with clinical outcome, complications and economic burden of the patient, provided accurate objective data for a better appreciation of global outcome, allowing for a preliminary view on long-term outcomes after PDR in adult low-grade isthmic spondylolisthesis, which were not presented in literature until now.     

Fluoridated elastomers: effect on the microbiology of plaque.

The objective of this study was to investigate the effect of fluoridated elastomeric ligatures on the microbiology of local dental plaque in vivo. This randomized, prospective, longitudinal, clinical trial had a split-mouth crossover design. The subjects were 30 patients at the beginning of their treatment with fixed orthodontic appliances in the orthodontic departments of the Liverpool and the Sheffield dental hospitals in the United Kingdom. The study consisted of 2 experimental periods of 6 weeks with a washout period between. Fluoridated elastomers were randomly allocated at the first visit to be placed around brackets on tooth numbers 12, 11, 33 or 22, 21, 43. Nonfluoridated elastomers were placed on the contralateral teeth. Standard nonantibacterial fluoridated toothpaste and mouthwash were supplied. After 6 weeks (visit 2), the elastomers were removed, placed in transport media, and plated on agar within 2 hours. Nonfluoridated elastomers were placed on all brackets for 1 visit to allow for a washout period. At visit 3, fluoridated elastomers were placed on the teeth contralateral to those that received them at visit 1. At visit 4, the procedures at visit 2 were repeated. Samples were collected on visits 2 and 4. A logistic regression was performed, with the presence or absence of streptococcal or anaerobic growth as the dependent variable. A mixed-effects analysis of variance was carried out with the percentage of streptococcal or anaerobic bacterial count as the dependent variable. The only significant independent variables were the subject variable (P =<.001) for the percentage of streptococcal and anaerobic bacterial count and the visit variable for the percentage of streptococcal count (P =<.001). The use of fluoridated or nonfluoridated elastomers was not significant for percentage of either streptococcal (P =.288) or anaerobic count (P =.230). Fluoridated elastomers are not effective at reducing local streptococcal or anaerobic bacterial growth after a clinically relevant time in the mouth.     

Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS.

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.     

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma.

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.