The effect of mannitol on oxidation-reduction potential in patients undergoing deceased donor renal transplantation-A randomized controlled trial.

BACKGROUND: Mannitol, an osmotic diuretic, is proposed to be an oxygen radical scavenger. Mannitol is often used in renal transplantation to attenuate oxidative stress and thus to protect renal graft function. We tested the hypothesis that mannitol reduces overall oxidative stress during deceased donor renal transplantation. METHODS: We randomly assigned 34 patients undergoing deceased donor renal transplantation to receive a solution of mannitol or placebo shortly before graft reperfusion until the end of surgery. We evaluated oxidative stress by measuring the static oxidative-reduction potential (sORP) and the capacity of the oxidative-reduction potential (cORP). sORP and cORP were measured pre-operatively, before and within 10 minutes after graft reperfusion, and post-operatively. RESULTS: Seventeen patients were enrolled in the mannitol group and 17 patients were enrolled in the placebo group. Mannitol had no significant effect on sORP (148.5 mV [136.2; 160.2]) as compared to placebo (143.6 mV [135.8; 163.2], P = .99). There was also no significant difference in cORP between the mannitol (0.22 µC [0.16; 0.36]) and the placebo group (0.22 µC [0.17; 0.38], P = .76). CONCLUSION: Mannitol showed no systemic redox scavenging effects during deceased donor renal transplantation. To evaluate the direct effect of mannitol on the renal graft further studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02705573.

Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation - a randomized controlled clinical trial.

BACKGROUND: Ischaemia/reperfusion (I/R) injury is associated with renal tissue damage during deceased donor renal transplantation. The effect of mannitol to reduce I/R injury during graft reperfusion in renal transplant recipients is based on weak evidence. We evaluated the effect of mannitol to reduce renal graft injury represented by 16 serum biomarkers, which are indicators for different important pathophysiological pathways. Our primary outcome were differences in biomarker concentrations between the mannitol and the placebo group 24 h after graft reperfusion. Additionally, we performed a linear mixed linear model to account biomarker concentrations before renal transplantation. METHODS: Thirty-four patients undergoing deceased donor renal transplantation were randomly assigned to receive either 20% mannitol or 0.9% NaCl placebo solution before, during, and after graft reperfusion. Sixteen serum biomarkers (MMP1, CHI3L1, CCL2, MMP8, HGF, GH, FGF23, Tie2, VCAM1, TNFR1, IGFBP7, IL18, NGAL, Endostatin, CystC, KIM1) were measured preoperatively and 24 h after graft reperfusion using Luminex assays and ELISA. RESULTS: Sixteen patients in each group were analysed. Tie2 differed 24 h after graft reperfusion between both groups (p = 0.011). Change of log2 transformed concentration levels over time differed significantly in four biomarkers (VCAM1,Endostatin, KIM1, GH; p = 0.007; p = 0.013; p = 0.004; p = 0.033; respectively) out of 16 between both groups. CONCLUSION: This study showed no effect of mannitol on I/R injury in patients undergoing deceased renal transplantation. Thus, we do not support the routinely use of mannitol to attenuate I/R injury. TRIAL REGISTRATION: NCT02705573 . Registered on 10th March 2016.

Endogenous arterial blood pressure increase after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Spontaneous blood pressure rise is a frequently observed phenomenon following aneurysmal subarachnoid hemorrhage (SAH). Facing the risk of aneurysmal rebleeding and the occurrence of delayed cerebral ischemia it is unclear how to react to these endogenous-driven blood pressure changes, as their predictive value for clinical course and functional outcome is still unknown. PATIENTS AND METHODS: Endogenous blood pressure characteristics within 21 days after SAH were retrospectively analyzed in 93 patients. Any use of vasopressors for active induction of hypertension marked the end of data collection. Mean arterial blood pressure (MAP) was related to the onset of cerebral vasospasm and patient characteristics (Hunt&Hess, age, pre-existing hypertension, antihypertensive therapy, sedation). Predictors for cerebral infarction and functional outcome were calculated using a logistic regression model. RESULTS: A significant MAP increase was observed in all patients from day 3 to day 7. Patients developing cerebral vasospasm had an overall steeper increase of MAP during this period (11.1 ± 11.4 mmHg vs. 6.5 ± 8.9 mmHg, p = 0.04). MAP rise started already 3 days before detection of vasospasm. Lower MAP values were recorded in patients with poor Hunt&Hess grade, under sedation and thus in patients with poor outcome. MAP had no impact on the development of cerebral infarction. In univariate analysis MAP on day 5 (OR 0.95, 95 %-CI: 0.89-0.99), MAP on day 6 (OR 0.95, 95 %-CI: 0.91-1.00), Hunt&Hess grade (OR 1.72, 95 %-CI: 1.14-2.60), sedation (OR 17.04, 95 %-CI: 2.08-139.51) and stroke (OR 5.82, 95 %-CI: 1.63-20.82) were predictors for poor outcome. In multivariable analysis, only sedation (OR 13.72, 95 %-CI: 1.62-115.94) and ischemic stroke (OR 4.48, 95 %-CI: 1.16-17.31) remained significant. CONCLUSION: Spontaneous MAP increase occured in all patients following SAH. It was highly influenced by clinical parameters, thereby limiting its prognostic value for functional outcome. However, a steep increase of MAP might be an early clinical marker to identify patients at risk for developing cerebral vasospasm.

Late gastrointestinal and urogenital side-effects after radiotherapy--incidence and prevalence. Subgroup-analysis within the prospective Austrian-German phase II multicenter trial for localized prostate cancer.

PURPOSE: In general late side-effects after prostate cancer radiotherapy are presented by the use of actuarial incidence rates. The aim of this analysis was to describe additional relevant aspects of late side effects after prostate cancer radiotherapy. MATERIALS AND METHODS: All 178 primary prostate-cancer patients were treated within the Austrian-German multicenter trial by three-dimensional radiotherapy up to a local dose of 70 Gy (low/intermediate-risk) or 74 Gy (high-risk), respectively. Late gastrointestinal/urogenital (GI/GU) side-effects were prospectively assessed by the use of EORTC/RTOG score. Maximum side-effects, actuarial incidence rate and prevalence rates, initial appearance and duration of ≥grade 2 toxicity were evaluated. RESULTS: Median follow-up was 74 months. Late GI/GU side-effects ≥grade 2 were detected in 15% (27/178) and 22% (40/178). The corresponding 5-year actuarial incidence rates for GI/GU side-effects were 19% and 23%, whereas the prevalence was 1-2% and 2-7% after 5 years, respectively. Late side effects ≥grade 2 appeared within 5 years after radiotherapy in all patients with GI side-effects (27/27) and in 85% (34/40) of the patients with GU side-effects, respectively and lasted for less than 3 years in 90% (GI) and 98% (GU). CONCLUSIONS: This study demonstrates that the majority of late GI and GU side effects after primary external beam radiotherapy for prostate cancer are transient. Using only actuarial incidence rates for reporting side effects may lead to misinterpretation or overestimation. The combination of incidence and prevalence rates provides a more comprehensive view on the complex issue of late side effects.

Comparison between external beam radiotherapy (70 Gy/74 Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients.

PURPOSE: Aim of this analysis was to compare biochemical no evidence of disease (bNED) rates in intermediate-risk prostate-cancer patients treated at two centres of excellence using different approaches: permanent interstitial brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 890 intermediate-risk prostate-cancer patients, who were treated from 1998 to 2008, were identified in the two local databases. In Utrecht 601 patients received I-125 BT applying a dose of 144 Gy. In Vienna 289 patients were treated by EBRT, applying a local dose of 70 Gy in 105 patients and 74 Gy in 184 patients. bNED-rates (Phoenix-definition) were assessed. RESULTS: Median follow-up was 48 months (1-150). 5-Year actuarial bNED-rates were 81% for BT-patients and 75% for EBRT-patients (67% for 70 Gy and 82% for 74 Gy), respectively. In univariate analysis no difference between BT and EBRT could be detected. In multivariate analysis including tumour-stage, GleasonScore, initial PSA, hormonal therapy and treatment-centre (BT vs. EBRT) only T-stage, GleasonScore and PSA were found to be significant. Additional analysis including radiation dose showed the same outcome. CONCLUSIONS: Intermediate-risk prostate cancer patients treated by permanent interstitial brachytherapy show biochemical tumour-control-rates which are comparable to EBRT of 74 Gy.

Prostate cancer radiotherapy in Austria: overview on number of patients, intention to treat, and treatment techniques based on data from 2007.

PURPOSE: Aim of this analysis was to assess the current status of prostate cancer radiotherapy in Austria and compare these numbers to patients treated with surgery. MATERIAL AND METHODS: A questionnaire was sent to all 14 Austrian departments asking about numbers of prostate cancer patients treated and indication of treatment (primary, postoperative), as well as the treatment technique used (3D-CRT, IMRT, brachytherapy), treatment volumes (with/without pelvic irradiation), dose applied, and differences in treatment concepts. Data investigated were based on the year 2007. RESULTS: Of the 14 departments (65%), 9 departments decided to participate. A total of 1,191 prostate cancer patients were treated (847 primary, 344 postoperative). Primary patients were treated by external beam technique (91%) and permanent interstitial brachytherapy (9%). All postoperative patients were treated by 3D-CRT. Dose ranged from 70-78 Gy for primary patients and from 60-72 Gy for postoperative patients. A risk-adapted dose prescription was performed in 5 centers. Additional pelvic lymph node irradiation was based on signs of positive nodes in 4 departments and based on Roach formula/Partin table in 5 departments. CONCLUSION: About 25% of prostate cancer patients receive primary radiotherapy. This number reflects a high potential to conduct national studies. Treatment technique and dose applied was in all centers investigated in accordance with the German S3 guidelines.