HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126620",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=126580",
"results": [
{
"text": "\n182191\n[Outpatient treatment of acute injuries of upper extremities with axillary plexus anesthesia in the emergency department-Is that possible without continuous anesthesia attendance?]\n\nRand, A\n\nAvila González, CA\n\nFeigl, GC\n\nMäcken, T\n\nWeiß, T\n\nZahn, PK\n\nLitz, RJ\n\nBeiträge in Fachzeitschriften\nISI:000529485200002\n32346777.0\n10.1007/s00101-020-00772-z\nNone\nThe incorporation into the routine operating procedure of patients with small but acute hand and forearm injuries requiring surgery who present in the emergency admission department, represents a challenge due to limited resources. The prompt treatment in the emergency admission department represents an alternative. This article retrospectively reports the authors' experiences with a treatment algorithm in which emergency patients were treated by ultrasound-guided axillary brachial plexus blocks (ABPB) and surgery carried out in the emergency department without further anesthesia attendance.\n Patients were preselected by the surgeon if they were suitable for a standardized treatment without anesthesia attendance during surgery. If there were no anesthesiological or surgical contraindications patients received an ABPB in the holding area of the operating room (OR) under standard monitoring. Blocks were performed as a multi-injection, ultrasound-guided technique which is anatomically described in detail. Patients >60 kg received a total volume of 30 ml of a mixture of 10 ml 1% ropivacaine (100 mg) and 20 ml 2% prilocaine (400 mg). Patients <60 kg received the same mixture with a reduced volume of 25 ml corresponding to 82.5 mg ropivacaine and 332.5 mg prilocaine. After controlling for block success patients were admitted to the emergency department and the surgical procedure was carried out under supervision by the surgeon without further anesthesia attendance. At discharge patients were explicitly instructed that in the case of any complications or a continuation of the block for more than 24 h they should contact the emergency department.\n Between January 2013 and November 2017 a total of 566 patients (46.4 years, range 11-88 years, 174.9 cm, range 140-211cm, 80.8 kg, range 42-178kg, ASA 1/2/3, 190/338/38, respectively) were treated according to a standardized protocol. The ABPBs were performed by 74 anesthetists. In 5% of the patients the initial block was incomplete and rescue blocks were performed with a maximum of 2‑3ml 1% prilocaine per corresponding nerve. After completion the block was ensured and all patients underwent surgery without further analgesics or local anesthetic infiltration by the surgeon. Complications related to the ABPB and readmissions were not observed.\n It could be demonstrated that minor surgery could be carried out safely and effectively with a defined algorithm using ABPB in selected patients outside the OR without permanent anesthesia attendance: however, indispensable prerequisites for such procedures are careful patient selection, patient compliance, the safe and effective performance of the ABPB and reliable agreement with the surgeon.\n\n\n"
},
{
"text": "\n656\nDaily oral magnesium supplementation suppresses bone turnover in young adult males.\n\nDimai, HP\n\nPorta, S\n\nWirnsberger, G\n\nLindschinger, M\n\nPamperl, I\n\nDobnig, H\n\nWilders-Truschnig, M\n\nLau, KH\n\nBeiträge in Fachzeitschriften\nISI:000075265300022\n9709941.0\n10.1210/jcem.83.8.5015\nNone\nThis study examined the effects of daily oral magnesium (Mg) supplementation on bone turnover in 12 young (27-36 yr old) healthy men. Twelve healthy men of matching age, height, and weight were recruited as the control group. The study group received orally 15 mmol Mg (Magnosolv powder, Asta Medica) daily in the early afternoon with 2-h fasting before and after Mg intake. Fasting blood and second void urine samples were collected in the early morning on days 0, 1, 5, 10, 20, and 30, respectively. Total and ionized Mg2+ and calcium (Ca2+), and intact PTH (iPTH) levels were determined in blood samples. Serum biochemical markers of bone formation (i.e. C-terminus of type I procollagen peptide and osteocalcin) and resorption (i.e. type I collagen telopeptide) and urinary Mg level adjusted for creatinine were measured. In these young males, 30 consecutive days of oral Mg supplementation had no significant effect on total circulating Mg level, but caused a significant reduction in the serum ionized Mg+ level after 5 days of intake. The Mg supplementation also significantly reduced the serum iPTH level, which did not appear to be related to changes in serum Ca2+ because the Mg intake had no significant effect on serum levels of either total or ionized Ca2+. There was a strong positive correlation between serum iPTH and ionized Mg2+ (r = 0.699; P < 0.001), supporting the contention that decreased serum iPTH may be associated with the reduction in serum ionized Mg2+. Mg supplementation also reduced levels of both serum bone formation and resorption biochemical markers after 1-5 days, consistent with the premise that Mg supplementation may have a suppressive effect on bone turnover rate. Covariance analyses revealed that serum bone formation markers correlated negatively with ionized Mg2+ (r = -0.274 for type I procollagen peptide and -0.315 for osteocalcin), but not with iPTH or ionized Ca2+. Thus, the suppressive effect on bone formation may be mediated by the reduction in serum ionized Mg2+ level (and not iPTH or ionized Ca2+). In summary, this study has demonstrated for the first time that oral Mg supplementation in normal young adults caused reductions in serum levels of iPTH, ionized Mg2+, and biochemical markers of bone turnover. In conclusion, oral Mg supplementation may suppress bone turnover in young adults. Because increased bone turnover has been implicated as a significant etiological factor for bone loss, these findings raise the interesting possibility that oral Mg supplementation may have beneficial effects in reducing bone loss associated with high bone turnover, such as age-related osteoporosis.\n\nDimai, Hans\n\nWirnsberger, Gerhard\n\n\n"
},
{
"text": "\n2882\nImaging of static brain lesions in vascular dementia: Implications for clinical trials\n\nErkinjuntti, T\n\nBowler, JV\n\nDeCarli, CS\n\nFazekas, F\n\nInzitari, D\n\nO'Brien, JT\n\nPantoni, L\n\nRockwood, K\n\nScheltens, P\n\nWahlund, LO\n\nDesmond, DW\n\nBeiträge in Fachzeitschriften\nISI:000084471900013\nNone\n10.1097/00002093-199912003-00013\nNone\nVascular dementia (VaD) relates to different vascular mechanisms and changes in the brain and has different causes and clinical manifestations, reflecting complex interactions between vascular etiologies, changes in the brain, host factors, and cognition. Critical elements to the concept and diagnosis of VaD are defining the vascular causes, the vascular etiologies, and changes in the brain. Verifying the relation between brain lesions and cognition (i.e., the extent to which brain changes cause, compound or coexist with cognitive impairment) and establishing the types, extent, side, site, and tempo of brain lesions that relate to incident cognitive impairment are major diagnostic challenges. Previous work on interactions between brain lesion and cognition in to cerebrovascular disease (CVD) have shown variation in the definitions and measures of cognitive impairment, in the techniques and methods used to reveal different brain changes, and in the selection of patient populations. Furthermore, small sample sizes and the absence of multivariate statistics have been design limitations. Accordingly, the different sets of criteria used and methods applied identify different numbers and clusters of subjects and different distribution of brain changes. Furthermore, this heterogeneity is reflected in variation in natural history such as the rate of progression of decline in different cognitive domains over time. All these factors have hampered optimal designs of clinical drug trials. A summary of generalizations regarding lesion and cognition interaction in VaD can be made. (1) Not a single feature, but a combination of infarct features-extent and type of white matter lesions (WMLs), degree and site of atrophy, and host factor characteristics-constitues correlates of VaD. (2) Infarct features favoring VaD include bilaterality, multiplicity (>1), location in the dominant hemisphere, and location in the limbic structures (fronto- and mediolimbic). (3) WML features favoring VaD are extensive Whits (extensive periventricular WMLs and confluent to extensive WMLs in the deep WM). (4) It is doubtful that only a single small lesion could provide imaging evidence for a diagnosis of VaD. (5) Absence of CVD lesions on computed tomography or magnetic resonance imaging is strong evidence against a diagnosis of VaD. In forthcoming protocols on CVD-associated cognitive impairment, the following brain imaging features should be specified: detailed characterization of brain changes; use of possible predefined subtypes based on brain imaging; use of rating of vascular burden; defining the type and extent of WMLs favoring a diagnosis of VaD; defining the extent of medial temporal lobe atrophy disfavoring a diagnosis of VaD; and technical harmonization of methods of scanning and analysis.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n68291\nImpact of heart rhythm status on registration accuracy of the left atrium for catheter ablation of atrial fibrillation.\n\nDong, J\n\nDalal, D\n\nScherr, D\n\nCheema, A\n\nNazarian, S\n\nBilchick, K\n\nAlmasry, I\n\nCheng, A\n\nHenrikson, CA\n\nSpragg, D\n\nMarine, JE\n\nBerger, RD\n\nCalkins, H\n\nBeiträge in Fachzeitschriften\nISI:000250985800009\n17850289.0\n10.1111/j.1540-8167.2007.00956.x\nNone\nRegistration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patient's heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied.\n This study included 10 patients who underwent AF ablation. Prior to the ablation procedure, the patients had contrast-enhanced cardiac CT scan obtained during SR (n = 7) or AF (n = 3). Using an image integration system (CartoMerge, Biosense Webster Inc.), LA CT surface reconstruction was registered to the real-time mapping space represented by the LA electroanatomic map. To determine the effect of rhythm change on registration accuracy, LA registration was performed during both SR and AF in each study subject. The distance between the surface of the registered LA CT reconstruction and multiple real-time LA electroanatomic map points (surface-to-point distance) was used as an index for LA registration error. The position error after rhythm change was defined as the surface-to-point distance between the surface of the LA CT reconstruction registered in the initial rhythm and the LA electroanatomic map points sampled during the second rhythm.\n A total of 90 +/- 12 and 92 +/- 9.5 LA electroanatomic map points were sampled for registration during SR and AF, respectively. No significant difference was found in surface-to-point distance when comparing SR with AF as the underlying rhythm during registration (1.91 +/- 0.24 vs 1.84 +/- 0.38 mm, P = 0.60). The position error after rhythm change was not different from the surface-to-point distance of LA registration conducted during the initial rhythm (2.05 +/- 0.39 vs 1.96 +/- 0.29 mm, P = 0.4). The surface-to-point distance did not differ when comparing LA registration conducted during the same versus different rhythm from that during CT imaging (1.96 +/- 0.29 vs 1.79 +/- 0.32 mm, P = 0.13).\n Registration error did not differ between LA registrations conducted during the same versus different rhythm as was present during CT imaging. Rhythm changes between SR and AF did not introduce significant error to the LA registration process for catheter ablation of AF. These findings are reassuring and suggest that reregistration is not needed if a patient's rhythm changes from SR to AF or vice versa during an ablation procedure.\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n131759\nPerinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE).\n\nLees, C\n\nMarlow, N\n\nArabin, B\n\nBilardo, CM\n\nBrezinka, C\n\nDerks, JB\n\nDuvekot, J\n\nFrusca, T\n\nDiemert, A\n\nFerrazzi, E\n\nGanzevoort, W\n\nHecher, K\n\nMartinelli, P\n\nOstermayer, E\n\nPapageorghiou, AT\n\nSchlembach, D\n\nSchneider, KT\n\nThilaganathan, B\n\nTodros, T\n\nvan Wassenaer-Leemhuis, A\n\nValcamonico, A\n\nVisser, GH\n\nWolf, H\n\nTRUFFLE Group\n\nBeiträge in Fachzeitschriften\nISI:000325082200007\n24078432.0\n10.1002/uog.13190\nNone\nObjectivesFew data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery. MethodsWe report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26-32 weeks of gestation, with abdominal circumference < 10(th) percentile and umbilical artery Doppler pulsatility index > 95(th) percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis. ResultsFive-hundred and three of 542 eligible women formed the study group. Mean SD gestational age at diagnosis was 29 +/- 1.6 weeks and mean +/- SD estimated fetal weight was 881 +/- 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 +/- 2.3 weeks, and birth weight was 1013 +/- 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 +/- 251 g) and born earlier (29.6 +/- 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome. ConclusionsFetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions. Copyright (c) 2013 ISUOG. Published by John Wiley & Sons Ltd.\n\n\n"
},
{
"text": "\n177341\nNewly Diagnosed Metastatic Intracranial Ependymoma in Children: Frequency, Molecular Characteristics, Treatment, and Outcome in the Prospective HIT Series.\n\nBenesch, M\n\nMynarek, M\n\nWitt, H\n\nWarmuth-Metz, M\n\nPietsch, T\n\nBison, B\n\nPfister, SM\n\nPajtler, KW\n\nKool, M\n\nSchüller, U\n\nPietschmann, K\n\nJuhnke, BO\n\nTippelt, S\n\nFleischhack, G\n\nSchmid, I\n\nKramm, CM\n\nVorwerk, P\n\nBeilken, A\n\nClassen, CF\n\nHernáiz Driever, P\n\nKropshofer, G\n\nImschweiler, T\n\nLemmer, A\n\nKortmann, RD\n\nRutkowski, S\n\nvon Hoff, K\n\nBeiträge in Fachzeitschriften\nISI:000485972100013\n30850560.0\n10.1634/theoncologist.2018-0489\nPMC6738295\nData on frequency, clinical presentation, and outcome of primary metastatic intracranial ependymoma in children are scarce.\n Prospective data on patients younger than 21 years with metastatic intracranial ependymoma at first diagnosis, registered from 2001 to 2014 in the HIT-2000 trial and the HIT-2000 Interim Registry, were analyzed.\n Of 453 registered patients with intracranial ependymoma and central neuropathology review, initial staging included spinal magnetic resonance imaging in all patients and lumbar cerebrospinal fluid (CSF) analysis in 402 patients. Ten patients (2.2%) had metastatic disease, including three with microscopic CSF positivity only (M1 metastasis stage, 0.7% of patients with CSF staging). Location of the primary tumor was supratentorial in four patients (all supratentorial RELA-fused ependymoma [ST-EPN-RELA]) and within the posterior fossa in five patients (posterior fossa ependymoma type A [PF-EPN-A], n = 4; posterior fossa ependymoma not further classifiable, n = 1), and multifocal in one patient.All four patients with ST-EPN-RELA were alive in first or second complete remission (CR) 7.5-12.3 years after diagnosis. All four patients with macroscopic metastases of posterior fossa or multifocal ependymoma died. Three patients with initial M1 stage (ST-EPN-RELA, n = 1; PF-EPN-A, n = 2) received chemotherapy and local irradiation and were alive in second or third CR 3.0-9.7 years after diagnosis. Progression-free and overall survival of the entire cohort at 5 years was 13% (±6%), and 58% (±16%), respectively.\n Primary metastatic disease is rare in children with intracranial ependymoma. Prognosis may depend on molecular subgroup and extent of dissemination, and relevance of CSF analysis for initial staging remains to be clarified.\n Childhood ependymoma presenting with metastasis at first diagnosis is very rare with a frequency of 2.4% in this population-based, well-characterized cohort. Detection of microscopic metastases in the cerebrospinal fluid was extremely rare, and impact on prognosis and respective treatment decision on irradiation field remains unclear. Initial metastatic presentation occurs in both supratentorial RELA-fused ependymoma and posterior fossa ependymoma. Prognosis may differ according to extent of metastasis and biological subgroup, with poor prognosis in diffusely spread metastatic posterior fossa ependymoma even after combination therapy with both intensive chemotherapy and craniospinal irradiation, which may help to guide individual therapeutic decisions for future patients.\n © AlphaMed Press 2019.\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n107758\nPituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus\n\nFeigl, GC\n\nPistracher, K\n\nBerghold, A\n\nMokry, M\n\nBeiträge in Fachzeitschriften\nISI:000284565300024\n21222294.0\n10.3171/2010.8.GKS10959\nNone\nObject. Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. Methods. A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. Results. Compete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1-81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus (p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5 Gy to the pituitary g land (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients (77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time in patients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). Conclusions. Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy. Very low radiation (loses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose. (DOI: 10.3171/2010.8.GKS10959)\n\nBerghold, Andrea\n\nMokry, Michael\n\nPistracher, Karin Felicitas\n\n\n"
},
{
"text": "\n142562\nValidation of the human activity profile questionnaire in patients after allogeneic hematopoietic stem cell transplantation.\n\nHerzberg, PY\n\nHeussner, P\n\nMumm, FH\n\nHorak, M\n\nHilgendorf, I\n\nvon Harsdorf, S\n\nHemmati, P\n\nRieger, K\n\nGreinix, H\n\nFreund, M\n\nLee, SJ\n\nHoller, E\n\nWolff, D\n\nBeiträge in Fachzeitschriften\nISI:000284566900010\n20541028.0\n10.1016/j.bbmt.2010.05.018\nNone\nChronic graft-versus-host disease (cGVHD) associated morbidity and mortality remain major barriers for successful allogeneic hematopoietic stem cell transplantation (alloHSCT). Currently, no reliable measures are established to monitor cGVHD activity changes for use in clinical trials. The Human Activity Profile (HAP) patient self-report was proposed by the National Institutes of Health (NIH) cGVHD consensus project as an independent measure of patients' functional status that could also indirectly reflect improvement of cGVHD, but that has not been validated in an alloHSCT patient population. One hundred seventy-six patients (median age 44 years [range: 18-72 years] after alloHSCT were evaluated with a German translation of the HAP, the NIH criteria-based cGVHD activity assessment, the Lee cGVHD Symptom-Scale, FACT-BMT, SF36, Berlin Social Support Scale, 24-Item Adjective Measure (24-AM), Hospital Anxiety and Depression Scale, and the NCCN-Distress-Thermometer. Enrollment occurred a median of 286 (range: 85-4003) days after alloHSCT. Follow-up surveys were conducted at 1, 2, 3, 5, 8, and 12 months after the baseline survey. Although 117 patient had cGVHD at time of enrollment (mild n = 33, moderate n = 50, or severe n = 34), 59 patients were included into the study in the absence of cGVHD between days 85 and 395 after transplantation. The maximum activity score (MAS) and adjusted activity score (AAS) of the HAP correlated inversely with grading of cGVHD severity (mild, moderate, or severe) (r = -0.25 for MAS and -0.24 for AAS). Lung manifestations of cGVHD correlated with AAS (r = 0.17), but not with MAS. HAP scores correlated with subscales from other instruments measuring physical domains, especially the physical functioning scale of the SF36. Performance was improved by use of an HSCT-modified HAP scoring system that excluded activities prohibited within the first year after alloHSCT. No significant correlation of the HAP was found with personality, age, sex, symptom burden, or social functioning or social well-being. Moreover, the HAP displayed a higher sensitivity to change of cGVHD activity compared to the SF36 and the FACT-BMT. In addition, steroid myopathy correlated with both HAP scores, but not the SF36. The HAP is a simple and valid questionnaire for the evaluation of the physical activity in patients after alloHSCT, with the advantage of detecting changes in cGVHD status independently of other quality-of-life measures and with a superior sensitivity compared to the SF36.\n Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n159183\nIncreased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder.\n\nBirner, A\n\nPlatzer, M\n\nBengesser, SA\n\nDalkner, N\n\nFellendorf, FT\n\nQueissner, R\n\nPilz, R\n\nRauch, P\n\nMaget, A\n\nHamm, C\n\nHerzog-Eberhard, S\n\nMangge, H\n\nFuchs, D\n\nMoll, N\n\nZelzer, S\n\nSchütze, G\n\nSchwarz, M\n\nReininghaus, B\n\nKapfhammer, HP\n\nReininghaus, EZ\n\nBeiträge in Fachzeitschriften\nISI:000395934400030\n28241062.0\n10.1371/journal.pone.0172699\nPMC5328271\nBipolar disorder (BD) is a chronic psychiatric disease which can take most different and unpredictable courses. It is accompanied by unspecific brainstructural changes and cognitive decline. The neurobiological underpinnings of these processes are still unclear. Emerging evidence suggests that tryptophan catabolites (TRYCATs), which involve all metabolites of tryptophan towards the kynurenine (KYN) branch, are involved in the etiology as well as in the course of BD. They are proposed to be mediators of immune-inflammation and neurodegeneration. In this study we measured the levels of KYN and its main catabolites consisting of the neurotoxic hydroxykynurenine (3-HK), the more neuroprotective kynurenic acid (KYNA) and anthranilic acid (AA) and evaluated the ratios between end-products and substrates as proxies for the specific enzymatic activity (3-HK/KYN, KYNA/KYN, AA/KYN) as well as 3-HK/KYNA as a proxy for neurotoxic vs. neuroprotective end-product relation in individuals with BD compared to healthy controls (HC).\n We took peripheral TRYCAT blood levels of 143 euthymic to mild depressive BD patients and 101 HC. For statistical analyses MANCOVA's controlled for age, sex, body mass index, cardiovascular disease and smoking were performed.\n The levels of KYNA (F = 5, 79; p <.05) were reduced in BD compared to HC. The enzymatic activity of the kynurenine-3-monooxygenase (KMO) reflected by the 3-HK/KYN ratio was increased in BD individuals compared to HC (F = 5, 94; p <.05). Additionally the ratio of 3-HK/KYNA was increased in individuals with BD compared to healthy controls (F = 11, 57; p <.01).\n In conclusion our findings subserve the concept of KYN -pathway alterations in the pathophysiology of BD. We present evidence of increased breakdown towards the neurotoxic branch in KYN metabolism even in a euthymic to mild depressive state in BD. From literature we know that depression and mania are accompanied by inflammatory states which should be capable to produce an even greater imbalance due to activation of key enzymes in the neurotoxic direction of KYN -conversion. These processes could finally be involved in the development of unspecific brain structural changes and cognitive deficits which are prevalent in BD. Further research should focus on state dependent changes in TRYCATs and its relation to cognition, brain structure and staging parameters.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nHamm, Carlo\n\nKapfhammer, Hans-Peter\n\nMaget, Alexander\n\nMangge, Harald\n\nPilz, Rene\n\nPlatzer, Martina\n\nQueissner, Robert\n\nReininghaus, Eva\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n179277\nCerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial.\n\nHansen, ML\n\nPellicer, A\n\nGluud, C\n\nDempsey, E\n\nMintzer, J\n\nHyttel-Sørensen, S\n\nHeuchan, AM\n\nHagmann, C\n\nErgenekon, E\n\nDimitriou, G\n\nPichler, G\n\nNaulaers, G\n\nCheng, G\n\nGuimarães, H\n\nTkaczyk, J\n\nKreutzer, KB\n\nFumagalli, M\n\nClaris, O\n\nLemmers, P\n\nFredly, S\n\nSzczapa, T\n\nAustin, T\n\nJakobsen, JC\n\nGreisen, G\n\nBeiträge in Fachzeitschriften\nISI:000506892200023\n31888764.0\n10.1186/s13063-019-3955-6\nPMC6937938\nCerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants.\n SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using 'opt-out' or deferred consent). Exclusion criteria will be no parental informed consent (or if 'opt-out' is used, lack of a record that clinical staff have explained the trial and the 'opt-out' consent process to parents and/or a record of the parents' decision to opt-out in the infant's clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants.\n Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates.\n ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.\n\nPichler, Gerhard\n\n\n"
},
{
"text": "\n107708\nPost-Translational Derepression of Invertase Activity in Source Leaves via Down-Regulation of Invertase Inhibitor Expression Is Part of the Plant Defense Response.\n\nBonfig, KB\n\nGabler, A\n\nSimon, UK\n\nLuschin-Ebengreuth, N\n\nHatz, M\n\nBerger, S\n\nMuhammad, N\n\nZeier, J\n\nSinha, AK\n\nRoitsch, T\n\nBeiträge in Fachzeitschriften\nISI:000284951200008\n20833735.0\n10.1093/mp/ssq053\nNone\nThere is increasing evidence that pathogens do not only elicit direct defense responses, but also cause pronounced changes in primary carbohydrate metabolism. Cell-wall-bound invertases belong to the key regulators of carbohydrate partitioning and source-sink relations. Whereas studies have focused so far only on the transcriptional induction of invertase genes in response to pathogen infection, the role of post-translational regulation of invertase activity has been neglected and was the focus of the present study. Expression analyses revealed that the high mRNA level of one out of three proteinaceous invertase inhibitors in source leaves of Arabidopsis thaliana is strongly repressed upon infection by a virulent strain of Pseudomonas syringae pv. tomato DC3000. This repression is paralleled by a decrease in invertase inhibitor activity. The physiological role of this regulatory mechanism is revealed by the finding that in situ invertase activity was detectable only upon infection by P. syringae. In contrast, a high invertase activity could be measured in vitro in crude and cell wall extracts prepared from both infected and non-infected leaves. The discrepancy between the in situ and in vitro invertase activity of control leaves and the high in situ invertase activity in infected leaves can be explained by the pathogen-dependent repression of invertase inhibitor expression and a concomitant reduction in invertase inhibitor activity. The functional importance of the release of invertase from post-translational inhibition for the defense response was substantiated by the application of the competitive chemical invertase inhibitor acarbose. Post-translational inhibition of extracellular invertase activity by infiltration of acarbose in leaves was shown to increase the susceptibility to P. syringae. The impact of invertase inhibition on spatial and temporal dynamics of the repression of photosynthesis and promotion of bacterial growth during pathogen infection supports a role for extracellular invertase in plant defense. The acarbose-mediated increase in susceptibility was also detectable in sid2 and cpr6 mutants and resulted in slightly elevated levels of salicylic acid, demonstrating that the effect is independent of the salicylic acid-regulated defense pathway. These findings provide an explanation for high extractable invertase activity found in source leaves that is kept inhibited in situ by post-translational interaction between invertase and the invertase inhibitor proteins. Upon pathogen infection, the invertase activity is released by repression of invertase inhibitor expression, thus linking the local induction of sink strength to the plant defense response.\n\nHofstadler, Martina\n\n\n"
},
{
"text": "\n135922\nGerman Registry for Acute Aortic Dissection Type A (GERAADA): initial results].\n\nConzelmann, LO\n\nKrüger, T\n\nHoffmann, I\n\nRylski, B\n\nEaso, J\n\nOezkur, M\n\nKallenbach, K\n\nDapunt, O\n\nKarck, M\n\nWeigang, E\n\nTeilnehmenden GERAADA-Zentren\n\nBeiträge in Fachzeitschriften\nISI:000295129200007\n21887529.0\n10.1007/s00059-011-3512-x\nNone\nThe working group "Aortic Surgery and Interventional Vascular Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) set up the German registry for acute aortic dissection type A (GERAADA) in July 2006. This web-based database was developed to record data of patients who had undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to learn from analyzing the data of AADA patients how to improve the perioperative management and surgical treatment of patients with AADA and to identify possible parameters affecting patient risk and outcome.\n Between July 2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the multi-center, prospective GERAADA database by 50 cardiac surgery centers in German-speaking countries in Europe. Data on patients' preoperative and intraoperative status, postoperative complications, midterm results and circumstances of death were recorded. Data were analyzed to identify risk factors influencing the outcome of these patients. The Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the statistical analyses.\n Analyses from GERAADA reveal a thirty-day mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch surgery are safe during hypothermic circulatory arrest even without selective cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated, antegrade cerebral perfusion is strongly recommended during the entire arch intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated ascending aortic replacement versus ascending aortic replacement combined with aortic arch repair had no statistical relevant influence on 30-day mortality. AADA surgical results in elderly patients are more encouraging than those treated without surgery. Surgery is even feasible in octogenarians with a 35% mortality rate.\n The aim of this registry is to optimize AADA patients' medical care, thereby reducing their morbidity and mortality. AADA treatment should always involve open surgery. Initial analyses from GERAADA provide clinically relevant insights concerning patients with AADA, and may enable therapeutic recommendations for improving perioperative and surgical management. Our latest study detected significant influencing risk factors for the outcome of AADA patients and may contribute to a consensus in setting guidelines for standard medical treatment.\n A European Registry of Aortic Diseases ("EuRADa") is being established this year under the leadership of the "Vascular Domain" of the European Association for Cardio-Thoracic Surgery (EACTS). This database will collect parameters on all aortic diseases, dissection types A and B, aneurysms, perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic ruptures, and all potential treatment strategies (medical treatment, open surgical and endovascular).\n\n\n"
},
{
"text": "\n187951\nPretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.\n\nWagner, NB\n\nLenders, MM\n\nKühl, K\n\nReinhardt, L\n\nAndré, F\n\nDudda, M\n\nRing, N\n\nEbel, C\n\nStäger, R\n\nZellweger, C\n\nLang, R\n\nPaar, M\n\nGussek, P\n\nRichtig, G\n\nStürmer, SH\n\nKimeswenger, S\n\nOellinger, A\n\nForschner, A\n\nLeiter, U\n\nWeide, B\n\nGassenmaier, M\n\nSchraag, A\n\nKlumpp, B\n\nHoetzenecker, W\n\nBerking, C\n\nRichtig, E\n\nZiemer, M\n\nMangana, J\n\nTerheyden, P\n\nLoquai, C\n\nNguyen, VA\n\nGebhardt, C\n\nMeier, F\n\nDiem, S\n\nCozzio, A\n\nFlatz, L\n\nRöcken, M\n\nGarbe, C\n\nEigentler, TK\n\nBeiträge in Fachzeitschriften\nNone\n33986126.0\n10.1136/jitc-2021-002350\nPMC8126291\nCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.\n MGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB-IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.\n Pretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036).\n High pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.\n © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nRichtig, Erika\n\nRichtig, Georg\n\n\n"
},
{
"text": "\n152054\nValidity and Reliability of Dermoscopic Criteria Used to Differentiate Nevi From Melanoma: A Web-Based International Dermoscopy Society Study.\n\nCarrera, C\n\nMarchetti, MA\n\nDusza, SW\n\nArgenziano, G\n\nBraun, RP\n\nHalpern, AC\n\nJaimes, N\n\nKittler, HJ\n\nMalvehy, J\n\nMenzies, SW\n\nPellacani, G\n\nPuig, S\n\nRabinovitz, HS\n\nScope, A\n\nSoyer, HP\n\nStolz, W\n\nHofmann-Wellenhof, R\n\nZalaudek, I\n\nMarghoob, AA\n\nBeiträge in Fachzeitschriften\nISI:000379590100012\n27074267.0\n10.1001/jamadermatol.2016.0624\nPMC5451089\nThe comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied.\n To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms.\n This was a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets.\n Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: the ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity).\n A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95% CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95% CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95% CI, 2.9-3.7), border score of 6 (OR, 3.3; 95% CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95% CI, 2.7-3.7) (P < .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95% CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95% CI, 0.42-0.51), dark brown color (ICC, 0.40; 95% CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95% CI, 0.39-0.48). The Menzies method had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P < .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves.\n Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor.\n\nHofmann-Wellenhof, Rainer\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n179667\n[The recurrence of hepatitis C virus after liver transplantation].\n\nNemes, B\n\nSárváry, E\n\nGerlei, Z\n\nFazakas, J\n\nDoros, A\n\nNémeth, A\n\nGörög, D\n\nFehérvári, I\n\nMáthé, Z\n\nGálffy, Z\n\nPár, A\n\nSchuller, J\n\nTelegdy, L\n\nFehér, J\n\nLotz, G\n\nSchaff, Z\n\nNagy, P\n\nJáray, J\n\nLengyel, G\n\nBeiträge in Fachzeitschriften\nNone\n17932003.0\n10.1556/OH.2007.28176\nNone\nThe main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C.\n Authors present the results of liver transplantations performed due to HCV infection.\n The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report.\n Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence.\n An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.\n\n\n"
},
{
"text": "\n21941\nOrbital scintigraphy with the somatostatin receptor tracer 99mTc-P829 in patients with Graves' disease.\n\nBurggasser, G\n\nHurtl, I\n\nHauff, W\n\nLukas, J\n\nGreifeneder, M\n\nHeydari, B\n\nThaler, A\n\nWedrich, A\n\nVirgolini, I\n\nBeiträge in Fachzeitschriften\nISI:000185837400007\n14530465.0\nNone\nNone\nReceptors for somatostatin (SST) (SSTR) are expressed on various tumor cells as well as on activated lymphocytes. Previous data have shown that Tc-99m-P829 binds with high affinity to many different types of tumor cells as well as to leukocytes via the human hSSTR2, hSSTR3, and hSSTR5 target receptors. Consequently, Tc-99m-P829 was successfully introduced as a peptide tracer for tumor imaging. In this study, we evaluated the orbital uptake of Tc-99m-P829 in patients with active and inactive thyroid-associated orbitopathy (TAO), accompanied by lymphocyte infiltration in the acute stage and by muscle fibrosis in the chronic stage of the disease. Methods: To evaluate its clinical usefulness in Graves' disease, Tc-99m-P829 scintigraphy (approximate to740 MBq) was performed in 44 patients with TAO (median duration, 19 mo; range, 1-360 mo). The clinical activity of the orbital disease was graded by the NOSPECS (no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) classification of the American Thyroid Association, the clinical activity score (CAS), and the superonasal index (SNI). SPECT (360degrees) and planar studies were completed within 3 In after injection. Orbital (O) regions of interest (ROIs) were compared with temporoparietal and occipital (OCC) ROIs. Orbital uptake ratios in Graves' disease were compared with data obtained from lung cancer patients with no eye disease (n = 22). Results: Overall, Tc-99m-P829 biokinetics were the same in Graves' disease patients as in lung cancer patients, showing a rapid blood clearance and visualization of the facial bones within minutes of injection. In all control patients, the orbit appeared as a "cold area, whereas visual orbital accumulation of Tc-99m-P829 was found in patients with active TAO (O/OCC ratios: 1.26 +/- 0.04 vs. 1.69 +/- 0.04; P < 0.01, respectively). Patients with active eye disease (n = 25) presented with an increased orbital uptake of Tc-99m-P829 compared with patients with inactive disease (n = 19; O/OCC ratio: 1.12 +/- 0.05; P < 0.01). A statistically significant correlation was found between CAS and the orbital uptake (O/OCC ratio) values (r = 0.90), whereas no correlation could be documented regarding the NOSPECS classification as well as the SNI. Conclusion: In TAO, Tc-99m-P829 yields high orbital binding with good clinical correlation. The better image quality due to the high energy of technetium, the lower radiation dose for patients and personnel, and the short acquisition protocol favor SSTR scintigraphy with Tc-99m-P829 over In-111-labeled compounds. The in-house availability of the radiotracer and cost-effectiveness are further advantages.\n\nWedrich, Andreas\n\n\n"
},
{
"text": "\n170416\nIxazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).\n\nRinnerthaler, G\n\nGampenrieder, SP\n\nPetzer, A\n\nBurgstaller, S\n\nFuchs, D\n\nRossmann, D\n\nBalic, M\n\nEgle, D\n\nRumpold, H\n\nSinger, CF\n\nBartsch, R\n\nPetru, E\n\nMelchardt, T\n\nUlmer, H\n\nMlineritsch, B\n\nGreil, R\n\nBeiträge in Fachzeitschriften\nISI:000449340800005\n30400780.0\n10.1186/s12885-018-4979-0\nPMC6220453\nTriple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated. Clinical data are available for carboplatin plus bortezomib in metastatic ovarian and lung cancers showing remarkable antitumor activity and good tolerability (Mol Cancer 11:26 2012, J Thorac Oncol 4:87-92 2009, J Thorac Oncol 7:1032-1040, 2012). Based on this evidence, the phase I/II MBC-10 trial will evaluate the toxicity profile and efficacy of the second-generation proteasome inhibitor ixazomib in combination with carboplatin in patients with advanced TNBC.\n Patients with metastatic TNBC pretreated with at least one prior line of chemotherapy for advanced disease with a confirmed disease progression and measurable disease according to RECIST criteria 1.1 are eligible for this study. Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle. The phase I part of this study utilizes an alternate dose escalation accelerated titration design. After establishing the maximum tolerated dose (MTD), the efficacy and safety of the combination will be further evaluated (phase II, including 41 evaluable patients). All patients will continue on study drugs until disease progression, unacceptable toxicity or discontinuation for any other reason. Primary endpoint of the phase II is overall response rate, secondary endpoints include progression-free survival, safety, and quality of life. This trial is open for patient enrollment since November 2016 in six Austrian cancer centers. Accrual is planned to be completed within 2 years.\n Based on preclinical and clinical findings an ixazomib and carboplatin combination is thought to be effective in metastatic TNBC patients. The MBC-10 trial is accompanied by a broad biomarker program investigating predictive biomarkers for treatment response and potential resistance mechanisms to the investigational drug combination.\n EudraCT Number: 2016-001421-13 received on March 31, 2016, ClinicalTrials.gov Identifier: NCT02993094 first posted on December 15, 2016. This trial was registered prospectively.\n\nBalic, Marija\n\nPetru, Edgar\n\n\n"
},
{
"text": "\n134350\nHybrid brain-computer interfaces and hybrid neuroprostheses for restoration of upper limb functions in individuals with high-level spinal cord injury.\n\nRohm, M\n\nSchneiders, M\n\nMüller, C\n\nKreilinger, A\n\nKaiser, V\n\nMüller-Putz, GR\n\nRupp, R\n\nBeiträge in Fachzeitschriften\nISI:000327290600009\n24064256.0\n10.1016/j.artmed.2013.07.004\nNone\nThe bilateral loss of the grasp function associated with a lesion of the cervical spinal cord severely limits the affected individuals' ability to live independently and return to gainful employment after sustaining a spinal cord injury (SCI). Any improvement in lost or limited grasp function is highly desirable. With current neuroprostheses, relevant improvements can be achieved in end users with preserved shoulder and elbow, but missing hand function.\n The aim of this single case study is to show that (1) with the support of hybrid neuroprostheses combining functional electrical stimulation (FES) with orthoses, restoration of hand, finger and elbow function is possible in users with high-level SCI and (2) shared control principles can be effectively used to allow for a brain-computer interface (BCI) control, even if only moderate BCI performance is achieved after extensive training.\n The individual in this study is a right-handed 41-year-old man who sustained a traumatic SCI in 2009 and has a complete motor and sensory lesion at the level of C4. He is unable to generate functionally relevant movements of the elbow, hand and fingers on either side. He underwent extensive FES training (30-45min, 2-3 times per week for 6 months) and motor imagery (MI) BCI training (415 runs in 43 sessions over 12 months). To meet individual needs, the system was designed in a modular fashion including an intelligent control approach encompassing two input modalities, namely an MI-BCI and shoulder movements.\n After one year of training, the end user's MI-BCI performance ranged from 50% to 93% (average: 70.5%). The performance of the hybrid system was evaluated with different functional assessments. The user was able to transfer objects of the grasp-and-release-test and he succeeded in eating a pretzel stick, signing a document and eating an ice cream cone, which he was unable to do without the system.\n This proof-of-concept study has demonstrated that with the support of hybrid FES systems consisting of FES and a semiactive orthosis, restoring hand, finger and elbow function is possible in a tetraplegic end-user. Remarkably, even after one year of training and 415 MI-BCI runs, the end user's average BCI performance remained at about 70%. This supports the view that in high-level tetraplegic subjects, an initially moderate BCI performance cannot be improved by extensive training. However, this aspect has to be validated in future studies with a larger population.\n Copyright © 2013 Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n135621\nDisturbed tryptophan metabolism in cardiovascular disease.\n\nMangge, H\n\nStelzer, I\n\nReininghaus, EZ\n\nWeghuber, D\n\nPostolache, TT\n\nFuchs, D\n\nBeiträge in Fachzeitschriften\nISI:000334590300002\n24606499.0\n10.2174/0929867321666140304105526\nPMC4922792\nAtherosclerosis (AS), a major pathologic consequence of obesity, is the main etiological factor of cardiovascular disease (CVD), which is the most common cause of death in the western world. A systemic chronic low grade immune- mediated inflammation (scLGI) is substantially implicated in AS and its consequences. In particular, proinflammatory cytokines play a major role, with Th1-type cytokine interferon-γ (IFN-γ) being a key mediator. Among various other molecular and cellular effects, IFN-γ activates the enzyme indoleamine 2, -dioxygenase (IDO) in monocyte-derived macrophages, dendritic, and other cells, which, in turn, decreases serum levels of the essential amino acid tryptophan (TRP). Thus, people with CVD often have increased serum kynurenine to tryptophan ratios (KYN/TRP), a result of an increased TRP breakdown. Importantly, increased KYN/TRP is associated with a higher likelihood of fatal cardiovascular events. A scLGI with increased production of the proinflammatory adipokine leptin, in combination with IFN-γ and interleukin-6 (IL-6), represents another central link between obesity, AS, and CVD. Leptin has also been shown to contribute to Th1-type immunity shifting, with abdominal fat being thus a direct contributor to KYN/TRP ratio. However, TRP is not only an important source for protein production but also for the generation of one of the most important neurotransmitters, 5-hydroxytryptamine (serotonin), by the tetrahydrobiopterin-dependent TRP 5-hydroxylase. In prolonged states of scLGI, availability of free serum TRP is strongly diminished, affecting serotonin synthesis, particularly in the brain. Additionally, accumulation of neurotoxic KYN metabolites such as quinolinic acid produced by microglia, can contribute to the development of depression via NMDA glutamatergic stimulation. Depression had been reported to be associated with CVD endpoints, but it most likely represents only a secondary loop connecting excess adipose tissue, scLGI and cardiovascular morbidity and mortality. Accelerated catabolism of TRP is further involved in the pathogenesis of the anemia of scLGI. The pro-inflammatory cytokine IFN-γ suppresses growth and differentiation of erythroid progenitor cells, and the depletion of TRP limits protein synthesis and thus hemoglobin production, and, through reduction in oxygen supply, may contribute to ischemic vascular disease. In this review we discuss the impact of TRP breakdown and the related complex mechanisms on the prognosis and individual course of CVD. Measurement of TRP, KYN concentrations, and calculation of the KYN/TRYP ratio will contribute to a better understanding of the interplay between inflammation, metabolic syndrome, mood disturbance, and anemia, all previously described as significant predictors of an unfavorable outcome in patients with CVD. The review leads to a novel framework for successful therapeutic modification of several cardinal pathophysiological processes leading to adverse cardiovascular outcome.\n\nMangge, Harald\n\nReininghaus, Eva\n\nStelzer, Ingeborg\n\n\n"
},
{
"text": "\n151249\nSPECT-CT for topographic mapping of sentinel lymph nodes prior to gamma probe-guided biopsy in head and neck squamous cell carcinoma.\n\nWagner, A\n\nSchicho, K\n\nGlaser, C\n\nZettinig, G\n\nYerit, K\n\nLang, S\n\nKlug, C\n\nLeitha, T\n\nBeiträge in Fachzeitschriften\nISI:000225871100001\n15555515.0\n10.1016/j.jcms.2004.05.008\nNone\nLymphoscintigraphic planar imaging is a common procedure for sentinel lymph node imaging prior to lymph node biopsy, but fails to elucidate the specific lymphatic drainage. Composite functional/anatomical imaging (SPECT-CT) has the potential to enhance topographic orientation and diagnostic sensitivity of sentinel lymph node imaging, but has not yet been applied in the head and neck region.\n A total of 30 patients were investigated. Planar imaging was 5 min, 265 x 265, right and left lateral; 500 kilocounts (Kcts) and SPECT (GE Millenium VG Hawk Eye 6 degrees/30s. step, 128 x 128, slice thickness 4.42 mm). Scans were performed 60 min after intra-mucodermal injection of 0.1 ml of 20 MBq 99mTc nanocolloid in patients with squamous cell cancer of the head and neck. SPECT studies were analysed by filtered back projection (FBP: Hann (0.7) prefiltering, Butterworth (0.5) postfiltering) and reconstruction (OSEM: Post Filter Hamming (0.85), 2 Iterations) and independently viewed with the co-registered CT image (eNTEGRA Functional Anatomical Fusion Vers 2.0216). The results were validated by comparing the results of each method employed in all 30 cases and intraoperative gamma probe-guided sentinel lymph node biopsy with histological examination in 13 of these patients.\n The majority of patients had more than one sentinel node (mean 1.63, min. 0, max. 4). Seven out of the 30 studies demonstrated lymphatic flow to the contralateral side of the neck. Forty-nine sentinel nodes were identified by iteratively reconstructed SPECT-CT. Thirty-eight out of these 49 could be located in lymphoscintigraphic planar imaging, whereas only 24/49 were detected in filtered back projection, respectively. In 11 of the 30 cases, a clinically unpredictable pattern of lymphatic drainage was observed. No correlation was found between T stage or tumour location and the number of sentinel nodes detected. In one out of the 13 cases, in whom imaging was followed by intraoperative gamma probe-guided biopsy, no sentinel node could be detected with the probe in the proximity of the primary tumour, although the node was clearly discernible in the reconstructed SPECT-CT.\n Composite functional/anatomical imaging (SPECT-CT) is feasible for sentinel lymph node detection. It enhances topographic orientation and diagnostic sensitivity with more sentinel nodes being detectable than by planar lymphoscintigraphy alone. Planar imaging should be accompanied by iterative reconstructed SPECT-CT to identify lymph nodes adjacent to the primary lesion. Such nodes are easily overlooked by planar lymphoscintigraphy and intraoperative gamma probes, as the high activity at the injection site can obscure their detection.\n\n\n"
}
]
}