Manfred Berres

Time course of cerebrovascular autoregulation during extreme Trendelenburg position for robotic-assisted prostatic surgery.

Trendelenburg positioning in combination with pneumoperitoneum during robotic‐assisted prostatic surgery possibly impairs cerebrovascular autoregulation. If cerebrovascular autoregulation is disturbed, arterial hypertension might induce cerebral hyperaemia and brain oedema, while low arterial blood pressure can induce cerebral ischaemia. The time course of cerebrovascular autoregulation was investigated during use of the Trendelenburg position and a pneumoperitoneum for robotic‐assisted prostatic surgery using transcranial Doppler ultrasound. Cerebral blood flow velocity was correlated with arterial blood pressure and the autoregulation index (Mx) was calculated. In 23 male patients, Mx was assessed at baseline, after induction of general anaesthesia, during the Trendelenburg position (40–45°), and after repositioning. During the Trendelenburg position, Mx increased over time, indicating an impairment of cerebrovascular autoregulation. After repositioning, Mx recovered to baseline levels. It can be concluded that with longer durations of Trendelenburg position and pneumoperitoneum, cerebrovascular autoregulation deteriorates, and, therefore, blood pressure management should be adapted to avoid cerebral oedema and the duration of Trendelenburg position should be as short as possible.

Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium

IntroductionSepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis.MethodsCerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured daily during the first 4 days of sepsis. Diagnosis of a SAD was performed using the confusion assessment method for ICU (CAM-ICU) and, furthermore the predominant brain electrical activity in electroencephalogram (EEG) both at day 4 after reduction of sedation to RASS >-2.Results30 critically ill adult patients with severe sepsis or septic shock (APACHE II 32 ± 6) were included. AR was impaired at day 1 in 60%, day 2 in 59%, day 3 in 41% and day 4 in 46% of patients; SAD detected by CAM-ICU was present in 76 % of patients. Impaired AR at day 1 was associated with the incidence of SAD at day 4 (p = 0.035).ConclusionsAR is impaired in the great majority of patients with severe sepsis during the first two days. Impaired AR is associated with SAD, suggesting that dysfunction of AR is one of the trigger mechanisms contributing to the development of SAD.Trial registrationclinicalTrials.gov ID NCT01029080

GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma

Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.

Robotic assisted prostatic surgery in the Trendelenburg position does not impair cerebral oxygenation measured using two different monitors: A clinical observational study.

BACKGROUND Robotic assisted prostatic surgery is frequently used because of its reduced side-effects compared with conventional surgery. During surgery, an extreme Trendelenburg position and CO2 pneumoperitoneum are necessary, which may lead to cerebral oedema, can potentially reduce brain perfusion and therefore could impair cerebral oxygenation. Cerebral oxygen saturation can be measured non-invasively using near-infrared spectroscopy (NIRS). OBJECTIVE The hypothesis of the present study was that steep Trendelenburg positioning during robotic assisted prostatic surgery impairs cerebral oxygen saturation measured using two different NIRS monitors. DESIGN Clinical observational study. SETTING Primary care university hospital, study period from March 2012 to February 2013. PATIENTS A total of 29 patients scheduled for robotic assisted prostatic surgery in a steep Trendelenburg position. INTERVENTIONS Cerebral oxygen saturation was measured throughout anaesthesia using the INVOS sensor (a trend monitor using two infrared wavelengths) for one hemisphere and the FORE-SIGHT sensor (a monitor using four wavelengths of laser light to calculate absolute oxygen saturation) for the other hemisphere in an alternate randomisation. MAIN OUTCOME MEASURE Changes in cerebral oxygenation of more than 5% during surgery in the Trendelenburg position. RESULTS The median duration of Trendelenburg positioning was 190 (interquartile range 130 to 230) min. Cerebral oxygen saturation decreased with INVOS from 74 ± 5% at baseline to a lowest value of 70 ± 4% with a slope of −0.0129 min−1 (P <0.01) and with FORE-SIGHT from 72 ± 5% at baseline to a nadir of 70 ± 3% with a slope of −0.008 min−1 (P <0.01). Comparing INVOS with FORE-SIGHT, there was a good association, with a slope of 0.86 ± 0.04 (P <0.01). CONCLUSION Both monitors showed a clinically irrelevant decrease in cerebral oxygen saturation of less than 5% over 4 h in a steep Trendelenburg position combined with CO2 pneumoperitoneum in patients undergoing robotic assisted prostatic surgery. This extreme positioning seems to be acceptable with regard to cerebral oxygenation. TRIAL REGISTRATION clinicaltrials.gov Identifier: ID NCT01275898.

Serial Measurement of Static and Dynamic Cerebrovascular Autoregulation After Brain Injury

Background In patients with neuronal injury, the knowledge of the status of cerebrovascular autoregulation can help to optimize the management of the cerebral perfusion pressure. This study characterizes dynamic and static cerebrovascular autoregulation during the first 7 days after severe traumatic brain injury or intracranial hemorrhage. Methods After approval from the IRB, 16 patients were studied. Cerebral blood flow velocity (CBFV) was measured daily for the assessment of dynamic (10 patients) and static (16 patients) cerebrovascular autoregulation in both the middle cerebral arteries using the transcranial Doppler sonography. Dynamic cerebrovascular autoregulation (dAR) was measured using the cuff-deflation method and was expressed by the index of the dAR. The index of the static cerebrovascular autoregulation (sAR) was calculated from changes in the CBFV in relation to drug-induced alterations of the arterial blood pressure. For statistical analyses, t test and mixed effect model were used. Results Both dAR and sAR after brain injury were impaired in most of the patients. The chronologic sequence of the dAR at the ipsilateral injured hemisphere showed a significant decrease until day 4 followed by an incomplete recovery (P<0.002). Changes in sAR were similar, however, they did not gain statistical significance. CBFV was lower at day 1-2 after injury in comparison with day 4 to 7 (P<0.02). Conclusion Daily measured dAR and sAR were impaired after brain injury with a nadir on day 4 and consecutive incomplete recovery over time.

The Effects of Alveolar Ridge Preservation: A Meta-Analysis

PURPOSE The aim of this article was to analyze the horizontal, vertical, and histological effects of alveolar ridge preservation (ARP) versus the ones of unassisted socket healing, in the format of an up-to-date review and meta-analysis. MATERIALS AND METHODS An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published up to June 2014 to identify literature presenting data on the topic of ARP. Only randomized controlled trials, controlled clinical trials, and prospective trials were included for meta-analysis. RESULTS After screening 903 abstracts from the electronic database, we included 64 studies in qualitative and 18 in quantitative synthesis. Quality assessment characterized a medium risk of bias for the included literature. The meta-analysis showed a mean difference between test and control groups of approximately 1.31 to 1.54 mm in bucco-oral bone width and 0.91 to 1.12 mm in bone height. Additionally, the intergroup difference in percentage of vital bone was assessed to be inconclusive across the included studies. Implants could be inserted into the determined position without further augmentation in 90.1% of the experimental sites, while this was the case in only 79.2% of the control sockets. CONCLUSIONS Resorption of the alveolar ridge cannot be totally stopped by ARP, while it still can be prevented compared with unassisted healing. No reliable predictions on the histological effects could be made due to limited data. Further on, no recommendation for a specific technique of ARP could be made. In conclusion, there is still need for ongoing research on the topic, even though the lower percentage of implant sites that needed additional augmentation in test sockets seemed to bring a patient benefit.

Learning Curve and Fatigue Effect of Flicker Defined Form Perimetry

PURPOSE To evaluate the learning curve and fatigue effect of flicker defined form (FDF) perimetry. DESIGN Prospective cross-sectional study. MATERIAL AND METHODS One hundred forty-one eyes of 75 healthy subjects were included in the study. Every subject was measured 3 times on 3 different days within 3 months. Differences among the tests were analyzed for mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), reliability indices, test duration, and test points <5% and <0.5% in 75 right eyes on the basis of linear mixed models for repeated measurements. To assess the effect of fatigue, differences of MS, MD, and PSD values between 66 left and right eyes were evaluated regarding alterations between these 3 examinations. RESULTS After 3 test sessions, significant improvements were found in MS and MD among all 3 tests (P ≤ .01), and in PSD between test 1 and test 3 (P = .02). Test duration decreased significantly between tests 1 and 3 (P = .01); fixation-loss errors decreased significantly between tests 2 and 3 and between tests 1 and 3 (P = .02, respectively). Test points with p < 0.5% decreased significantly between tests 1 and 2 (P = .04) and 1 and 3 (P = .01) When comparing both eyes, MS, MD, and PSD were significantly better in first than in second eyes examined. CONCLUSIONS There exist significant learning and fatigue effects for repeated flicker defined form perimetry. For good and reliable results on FDF perimetry, at least 3 tests should be performed in an individual. Between the tests of both eyes, a rest should be offered.

Influence of beach chair position on cerebral oxygen saturation: a comparison of INVOS and FORE-SIGHT cerebral oximeter.

Background: Although beach chair position (BCP) is frequently used for shoulder surgery, a potentially detrimental influence on cerebral oxygenation is discussed. Therefore, the present study investigated changes in regional cerebral oxygen saturation (rSO2/StO2) during BCP comparing 2 different devices for near-infrared spectroscopy measurement. Methods: Data were collected in 35 patients undergoing shoulder surgery in BCP and compared with a control group of 35 awake volunteers. The rSO2/StO2 was assessed using INVOS and FORE-SIGHT monitors. Mean arterial blood pressure (MAP), peripheral oxygen saturation (SpO2), PeCO2, FiO2, end-tidal sevoflurane concentration, and rSO2/StO2 were measured before positioning, during BCP, and in supine position after surgery. Results: A decrease in rSO2/StO2 could be observed after BCP (INVOS: 76.1% supine vs. 66.7% BCP, P<0.001; FORE-SIGHT: 78.6% supine, 66.1% BCP, P<0.001), which was reversible in supine position. This decrease correlated with MAP during BCP, while in supine position no correlation was detected. In control group BCP did not influence rSO2/StO2. Changes detected with INVOS or FORE-SIGHT cerebral oximeter did not differ. Conclusion: BCP is associated with a decrease in rSO2/StO2 of 10% in anesthetized patients, which is reversible after repositioning. No changes occurred in supine position under general anesthesia as well as in awake subjects in BCP. This underlines the assumption that vasodilation by anesthetics in combination with BCP evoke a drop in rSO2/StO2. A strict hemodynamic management may be necessary to prevent desaturation events. Despite different technology used by the devices, the results of INVOS and FORE-SIGHT cerebral oximeters are comparable.

Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma.

INTRODUCTION Functional polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF-SNPs were determined. MATERIALS AND METHODS In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF-SNPs (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A, and -460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined. RESULTS After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF -2578 A/C and -460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs (T > 2 or N > 0) together with the -1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs (T > 2) could be confirmed (P = 0.002). DISCUSSION Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed.

l-additive measures on measure spaces

Abstract In his thesis, Sugeno has introduced a class of non-additive set functions gλ which have been called λ-additive measures. He has printed out that gλ can be represented by a density function, if it is defined on the power set of a finite set. In this article this concept is generalized for arbitrary measure spaces. Moreover, it is shown that any density function on a measure space determines a unique parameter λ ϵ (−1, ∞). As in the finite case, λ-additive measures are belief functions iff λ ⩾ 0 and plausibility functions iff λ ⩽ 0. The proof of this statement is achieved by a generally applicable reduction of the problem to finite σ-algebras.