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=125840",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=125800",
"results": [
{
"text": "\n181400\nEfficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial.\n\nAdlbrecht, C\n\nWurm, R\n\nDepuydt, P\n\nSpapen, H\n\nLorente, JA\n\nStaudinger, T\n\nCreteur, J\n\nZauner, C\n\nMeier-Hellmann, A\n\nEller, P\n\nLaenen, MV\n\nMolnár, Z\n\nVárkonyi, I\n\nSchaaf, B\n\nHéjja, M\n\nŠrámek, V\n\nSchneider, H\n\nKanesa-Thasan, N\n\nEder-Lingelbach, S\n\nKlingler, A\n\nDubischar, K\n\nWressnigg, N\n\nRello, J\n\nBeiträge in Fachzeitschriften\nISI:000521070200002\n32131866.0\n10.1186/s13054-020-2792-z\nPMC7057595\nPseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients.\n Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated.\n All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group.\n The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality.\n https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.\n\nEller, Philipp\n\n\n"
},
{
"text": "\n182383\nRivaroxaban in Peripheral Artery Disease after Revascularization.\n\nBonaca, MP\n\nBauersachs, RM\n\nAnand, SS\n\nDebus, ES\n\nNehler, MR\n\nPatel, MR\n\nFanelli, F\n\nCapell, WH\n\nDiao, L\n\nJaeger, N\n\nHess, CN\n\nPap, AF\n\nKittelson, JM\n\nGudz, I\n\nMátyás, L\n\nKrievins, DK\n\nDiaz, R\n\nBrodmann, M\n\nMuehlhofer, E\n\nHaskell, LP\n\nBerkowitz, SD\n\nHiatt, WR\n\nBeiträge in Fachzeitschriften\nISI:000536856000014\n32222135.0\n10.1056/NEJMoa2000052\nNone\nPatients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.\n In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome.\n A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007).\n In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).\n Copyright © 2020 Massachusetts Medical Society.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n185039\nEffectiveness of reverse total shoulder arthroplasty for primary and secondary fracture care: mid-term outcomes in a single-centre experience.\n\nSchwarz, AM\n\nHohenberger, GM\n\nSauerschnig, M\n\nNiks, M\n\nLipnik, G\n\nMattiassich, G\n\nZacherl, M\n\nSeibert, FJ\n\nPlecko, M\n\nBeiträge in Fachzeitschriften\nISI:000608282900005\n33419418.0\n10.1186/s12891-020-03903-0\nPMC7792308\nThe introduction of reverse total shoulder arthroplasty (RSA) as a treatment option in complex proximal humeral fractures, has significantly extended the surgical armamentarium. The aim of this study was to investigate the mid-term outcome following fracture RSA in acute or sequelae, as well as salvage procedures. It was hypothesized that revision RSA (SRSA) leads to similar mid-term results as primary fracture treatment by RSA (PRSA).\n This retrospective study describes the radiological and clinical mid-term outcomes in a standardized single-centre and Inlay design. Patients who underwent RSA in fracture care between 2008 and 2017 were included (minimum follow-up: 2 years, minimum age: 60 years). The assessment tools used for functional findings were range of motion (ROM), Visual Analogue Scale, absolute (CS) plus normative Constant Score, QuickDASH, and Subjective Shoulder Value. All adverse events as well as the radiological results and their clinical correlations were statistically analysed (using p < .05and 95% confidence intervals).\n Following fracture RSA, 68 patients were included (mean age: 72.5 years, mean follow-up: 46 months). Forty-two underwent primary RSA (PRSA), and 26 underwent revision RSA (SRSA). Adverse advents were observed in 13% (n = 9/68). No statistically significant results were found for the scores of the PRSA and SRSA groups, while the failed osteosynthesis SRSA subgroup obtained statistically significantly negative values for ROM subzones (flexion: p = .020, abduction: p = .020). Decreased instances of tubercle healing were observed for the in PRSA group relative to the SRSA group (p = .006). The absence of bony healing of the tubercles was related to significant negative clinical and subjective outcomes (all scores: p < .05, external rotation: p= .019). Significant postoperative improvements were evaluated in the SRSA group (CS: 23 to 56 at mean, p = .001), the time from index surgery to operative revision revealed no associations in functional findings.\n RSA is an effective option in severe shoulder fracture management with predictable results for salvage as well as first-line treatment. Promising mid-term functional results, reasonable implant survival rates, and high patient satisfaction can be achieved.\n Level III.\n\nHohenberger, Gloria\n\nPlecko, Michael\n\nSchwarz, Angelika\n\nSeibert, Franz\n\nZacherl, Maximilian\n\n\n"
},
{
"text": "\n4543\nDifferential peristaltic motor effects of prostanoid (DP, EP, IP, TP) and leukotriene receptor agonists in the guinea-pig isolated small intestine.\n\nShahbazian, A\n\nHeinemann, A\n\nPeskar, BA\n\nHolzer, P\n\nBeiträge in Fachzeitschriften\nISI:000179383900015\n12429577.0\n10.1038/sj.bjp.0704958\nPMC1573581\n1. Since the role of prostanoid receptors in intestinal peristalsis is largely unknown, the peristaltic motor effects of some prostaglandin (DP, EP, IP), thromboxane (TP) and leukotriene (LT) receptor agonists and antagonists were investigated. 2. Propulsive peristalsis in fluid-perfused segments from the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension sensitivity were deduced from alterations of the peristaltic pressure threshold and modifications of peristaltic performance were reflected by modifications of the amplitude, maximal acceleration and residual baseline pressure of the peristaltic waves. 3. Four categories of peristaltic motor effects became apparent: a decrease in distension sensitivity and peristaltic performance as induced by the EP1/EP3 receptor agonist sulprostone and the TP receptor agonist U-46619 (1-1000 nM); a decrease in distension sensitivity without a major change in peristaltic performance as induced by PGD(2) (3-300 nM) and LTD(4) (10-100 nM); a decrease in peristaltic performance without a major change in distension sensitivity as induced by PGE(1), PGE(2) (1-1000 nM) and the EP1/IP receptor agonist iloprost (1-100 nM); and a decrease in peristaltic performance associated with an increase in distension sensitivity as induced by the EP2 receptor agonist butaprost (1-1000 nM). The DP receptor agonist BW-245 C (1-1000 nM) was without effect. 4. The peristaltic motor action of sulprostone remained unchanged by the EP1 receptor antagonist SC-51089 (1 micro M) and the DP/EP1/EP2 receptor antagonist AH-6809 (30 micro M), whereas that of U-46619 and LTD(4) was prevented by the TP receptor antagonist SQ-29548 (10 micro M) and the cysteinyl-leukotriene(1) (cysLT(1)) receptor antagonist tomelukast (10 micro M), respectively. 5. These observations and their pharmacological analysis indicate that activation of EP2, EP3, IP, TP and cysLT(1) receptors, but not DP receptors, modulate intestinal peristalsis in a receptor-selective manner, whereas activation of EP1 seems to be without influence on propulsive peristalsis. In a wider perspective it appears as if the effect of prostanoid receptor agonists to induce diarrhoea is due to their prosecretory but not peristaltic motor action.\n\nHeinemann, Akos\n\nHolzer, Peter\n\nPeskar, Bernhard\n\n\n"
},
{
"text": "\n65836\nDetection of amplified DNA sequences by reverse chromosome painting using genomic tumor DNA as probe.\n\nJoos, S\n\nScherthan, H\n\nSpeicher, MR\n\nSchlegel, J\n\nCremer, T\n\nLichter, P\n\nBeiträge in Fachzeitschriften\nISI:A1993KN27800002\n8383093.0\nNone\nNone\nA modification of "reverse chromosome painting" was carried out using genomic DNA from tumor cells as a complex probe for chromosomal in situ suppression hybridization to normal metaphase chromosome spreads. Amplified DNA sequences contained in such probes showed specific signals, revealing the normal chromosome positions from which these sequences were derived. As a model system, genomic DNAs were analyzed from three tumor cell lines with amplification units including the proto-oncogene c-myc. The smallest amplification unit was about 90 kb and was present in 16-24 copies; the largest unit was bigger than 600 kb and was present in 16-32 copies. Specific signals that co-localized with a differently labeled c-myc probe on chromosome band 8q24 were obtained with genomic DNA from each cell line. In further experiments, genomic DNA derived from primary tumor material was used in the case of a male patient with glioblastoma multiforme (GBM). Southern blot analysis using an epidermal growth factor receptor gene (EGFR) probe that maps to 7p13 indicated the amplification of sequences from this gene. Using reverse chromosome painting, signals were found both on band 7p13 and bands 12q13-q15. Notably, the signal on 12q13-q15 was consistently stronger. The weaker 7p13 signal showed co-localization with the major signal of the differently labeled EGFR probe. A minor signal of this probe was seen on 12q13, suggesting cross-hybridization to ERB3 sequences homologous to EGFR. The results indicate co-amplification of sequences from bands 12q13-q15, in addition to sequences from band 7p13. Several oncogenes map to 12q13-q15 providing candidate genes for a tumor-associated proto-oncogene amplification. Although the nature of the amplified sequences needs to be clarified, this experiment demonstrates the potential of reverse chromosome painting with genomic tumor DNA for rapidly mapping the normal chromosomal localization of the DNA from which the amplified sequences were derived. In addition, a weaker staining of chromosomes 10 and X was consistently observed indicating that these chromosomes were present in only one copy in the GBM genome. This rapid approach can be used to analyze cases where no metaphase spreads from the tumor material are available. It does not require any preknowledge of amplified sequences and can be applied to screen large numbers of tumors.\n\nSpeicher, Michael\n\n\n"
},
{
"text": "\n68708\nStretch-dependent modulation of Na+i, Ca2+i, and pHi in rabbit myocardium--a mechanism for the slow force response.\n\nLuers, C\n\nFialka, F\n\nElgner, A\n\nZhu, D\n\nKockskämper, J\n\nvon Lewinski, D\n\nPieske, B\n\nBeiträge in Fachzeitschriften\nISI:000233469400016\n16099446.0\n10.1016/j.cardiores.2005.07.001\nNone\nObjective: Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca2+ sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na+/H+ exchange (NHEI) and consecutive changes in pH(i) and/or [Na+](i) may underlie the SFR. Methods: Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca2+ indicator aequorin, the pH indicator BCECF, or the Na+ indicator SBFI and rapidly stretched from 88% (L-88) to 98% (L-98) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca2+](i), [Na+](i), or pH(i) were quantified before and after inhibition of NHE I by HOE 642 (3 mu M) or reverse-mode Na+/Ca2+ exchange (NCX) by KB-R 7943 (5 mu M). Results: In both Tyrode (n=21) and HEPES (n=22), developed force increased to similar to 160% during the 1st phase followed by a further increase to similar to 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n =4; normalized to the 1st phase) and a similar to 3 mM increase in [Na+](i) (n =4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pHi increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by similar to 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na+](i) by 72% and the delayed alkalinization. Conclusions: The data are consistent with the hypothesis that SFR results from increases in [Ca2+](i) secondary to altered flux via NCX in part resulting from increases in [Na+]i mediated by NHE1 (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n155367\nMulti-port versus single-port cholecystectomy: results of a multi-centre, randomised controlled trial (MUSIC trial).\n\nArezzo, A\n\nPassera, R\n\nBullano, A\n\nMintz, Y\n\nKedar, A\n\nBoni, L\n\nCassinotti, E\n\nRosati, R\n\nFumagalli Romario, U\n\nSorrentino, M\n\nBrizzolari, M\n\nDi Lorenzo, N\n\nGaspari, AL\n\nAndreone, D\n\nDe Stefani, E\n\nNavarra, G\n\nLazzara, S\n\nDegiuli, M\n\nShishin, K\n\nKhatkov, I\n\nKazakov, I\n\nSchrittwieser, R\n\nCarus, T\n\nCorradi, A\n\nSitzman, G\n\nLacy, A\n\nUranues, S\n\nSzold, A\n\nMorino, M\n\nBeiträge in Fachzeitschriften\nISI:000405207100021\n27778171.0\n10.1007/s00464-016-5298-7\nNone\nSingle-port laparoscopic surgery as an alternative to conventional laparoscopic cholecystectomy for benign disease has not yet been accepted as a standard procedure. The aim of the multi-port versus single-port cholecystectomy trial was to compare morbidity rates after single-access (SPC) and standard laparoscopy (MPC).\n This non-inferiority phase 3 trial was conducted at 20 hospital surgical departments in six countries. At each centre, patients were randomly assigned to undergo either SPC or MPC. The primary outcome was overall morbidity within 60 days after surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov (NCT01104727).\n The study was conducted between April 2011 and May 2015. A total of 600 patients were randomly assigned to receive either SPC (n = 297) or MPC (n = 303) and were eligible for data analysis. Postsurgical complications within 60 days were recorded in 13 patients (4.7 %) in the SPC group and in 16 (6.1 %) in the MPC group (P = 0.468); however, single-access procedures took longer [70 min (range 25-265) vs. 55 min (range 22-185); P < 0.001]. There were no significant differences in hospital length of stay or pain VAS scores between the two groups. An incisional hernia developed within 1 year in six patients in the SPC group and in three in the MPC group (P = 0.331). Patients were more satisfied with aesthetic results after SPC, whereas surgeons rated the aesthetic results higher after MPC. No difference in quality of life scores, as measured by the gastrointestinal quality of life index at 60 days after surgery, was observed between the two groups.\n In selected patients undergoing cholecystectomy for benign gallbladder disease, SPC is non-inferior to MPC in terms of safety but it entails a longer operative time. Possible concerns about a higher risk of incisional hernia following SPC do not appear to be justified. Patient satisfaction with aesthetic results was greater after SPC than after MPC.\n\nUranüs, Selman\n\n\n"
},
{
"text": "\n159480\nMetabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet.\n\nOberbach, A\n\nHaange, SB\n\nSchlichting, N\n\nHeinrich, M\n\nLehmann, S\n\nTill, H\n\nHugenholtz, F\n\nKullnick, Y\n\nSmidt, H\n\nFrank, K\n\nSeifert, J\n\nJehmlich, N\n\nvon Bergen, M\n\nBeiträge in Fachzeitschriften\nISI:000398985700020\n28252966.0\n10.1021/acs.jproteome.6b00973\nNone\nThe gastrointestinal microbiota in the gut interacts metabolically and immunologically with the host tissue in the contact zone of the mucus layer. For understanding the details of these interactions and especially their dynamics it is crucial to identify the metabolically active subset of the microbiome. This became possible by the development of stable isotope probing techniques, which have only sparsely been applied to microbiome research. We applied the in vivo stable isotope approach using (15)N-labeled diet with subsequent identification of metabolically active bacterial species. Four-week old male Sprague-Dawley rats were randomly assigned to chow diet (CD, n =15) and high-fat diet (HFD, n =15). After 11 weeks, three animals from each group were sacrificed for baseline characterization of anthropometric and metabolic obesity. The remaining animals were exposed to either a (15)N-labeled (n =9) or a (14)N-unlabeled experimental diet (n =3). Three rats from each cohort (HFD and CD) were sacrificed at 12, 24, and 72 h. The remaining three animals from each cohort, which received the (14)N-unlabeled diet, were sacrificed after 72 h. The colon was harvested and divided into three equal sections (proximal, medial, and distal), and the mucus layer of each specimen was sampled by scraping. We identified the active subset in an HFD model of obesity in comparison with lean controls rats using metaproteomics. In addition, all samples were investigated by 16S rRNA amplicon gene sequencing. The active microbiome of the HFD group showed an increase in bacterial taxa for Verrucomicrobia and Desulfovibrionaceae. In contrast with no significant changes in alpha diversity, time- and localization-dependent effects in beta-diversity were clearly observed. In terms of enzymatic functions the HFD group showed strong affected metabolic pathways such as energy production and carbohydrate metabolism. In vivo isotope labeling combined with metaproteomics provides a valuable method to distinguish the active from the non-active bacterial phylogenetic groups that are relevant for microbiota-host interaction. For morbid obesity such analysis may provide potentially new strategies for targeted pre- or probiotic treatments.\n\nTill, Holger\n\n\n"
},
{
"text": "\n166039\nInterference and problem size effect in multiplication fact solving: Individual differences in brain activations and arithmetic performance.\n\nDe Visscher, A\n\nVogel, SE\n\nReishofer, G\n\nHassler, E\n\nKoschutnig, K\n\nDe Smedt, B\n\nGrabner, RH\n\nBeiträge in Fachzeitschriften\nISI:000430364100060\n29444466.0\n10.1016/j.neuroimage.2018.01.060\nNone\nIn the development of math ability, a large variability of performance in solving simple arithmetic problems is observed and has not found a compelling explanation yet. One robust effect in simple multiplication facts is the problem size effect, indicating better performance for small problems compared to large ones. Recently, behavioral studies brought to light another effect in multiplication facts, the interference effect. That is, high interfering problems (receiving more proactive interference from previously learned problems) are more difficult to retrieve than low interfering problems (in terms of physical feature overlap, namely the digits, De Visscher and Noël, 2014). At the behavioral level, the sensitivity to the interference effect is shown to explain individual differences in the performance of solving multiplications in children as well as in adults. The aim of the present study was to investigate the individual differences in multiplication ability in relation to the neural interference effect and the neural problem size effect. To that end, we used a paradigm developed by De Visscher, Berens, et al. (2015) that contrasts the interference effect and the problem size effect in a multiplication verification task, during functional magnetic resonance imaging (fMRI) acquisition. Forty-two healthy adults, who showed high variability in an arithmetic fluency test, participated in our fMRI study. In order to control for the general reasoning level, the IQ was taken into account in the individual differences analyses. Our findings revealed a neural interference effect linked to individual differences in multiplication in the left inferior frontal gyrus, while controlling for the IQ. This interference effect in the left inferior frontal gyrus showed a negative relation with individual differences in arithmetic fluency, indicating a higher interference effect for low performers compared to high performers. This region is suggested in the literature to be involved in resolution of proactive interference. Besides, no correlation between the neural problem size effect and multiplication performance was found. This study supports the idea that the interference due to similarities/overlap of physical traits (the digits) is crucial in memorizing arithmetic facts and in determining individual differences in arithmetic.\n Copyright © 2018 Elsevier Inc. All rights reserved.\n\nHassler, Eva Maria\n\nReishofer, Gernot\n\n\n"
},
{
"text": "\n174571\nA genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology.\n\nde Vries, PS\n\nSabater-Lleal, M\n\nHuffman, JE\n\nMarten, J\n\nSong, C\n\nPankratz, N\n\nBartz, TM\n\nde Haan, HG\n\nDelgado, GE\n\nEicher, JD\n\nMartinez-Perez, A\n\nWard-Caviness, CK\n\nBrody, JA\n\nChen, MH\n\nde Maat, MPM\n\nFrånberg, M\n\nGill, D\n\nKleber, ME\n\nRivadeneira, F\n\nSoria, JM\n\nTang, W\n\nTofler, GH\n\nUitterlinden, AG\n\nvan Hylckama Vlieg, A\n\nSeshadri, S\n\nBoerwinkle, E\n\nDavies, NM\n\nGiese, AK\n\nIkram, MK\n\nKittner, SJ\n\nMcKnight, B\n\nPsaty, BM\n\nReiner, AP\n\nSargurupremraj, M\n\nTaylor, KD\n\nINVENT Consortium\n\nMEGASTROKE Consortium of the International Stroke Genetics Consortium\n\nFornage, M\n\nHamsten, A\n\nMärz, W\n\nRosendaal, FR\n\nSouto, JC\n\nDehghan, A\n\nJohnson, AD\n\nMorrison, AC\n\nO'Donnell, CJ\n\nSmith, NL\n\nBeiträge in Fachzeitschriften\nISI:000461501400014\n30642921.0\n10.1182/blood-2018-05-849240\nPMC6396174\nFactor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n187002\nEffect of Negative Pressure Therapy on Open Abdomen Treatments. Prospective Randomized Study With Two Commercial Negative Pressure Systems.\n\nAuer, T\n\nSauseng, S\n\nDelcev, P\n\nKohek, P\n\nBeiträge in Fachzeitschriften\nISI:000619619800001\n33614699.0\n10.3389/fsurg.2020.596056\nPMC7894571\nIntroduction: The use of negative pressure dressings for open abdominal therapy has made a great impact on strategies for open abdominal treatment. Observed intestinal damage and developement of fistula formation raises questions about safety of commonly used systems (AB-Thera). The most common used system uses foils for shielding intestines directly from negative pressure. As an alternative a system with open pore dressing in double layer film was introduced (Suprasorb CNP) and proved to safe in animal studies. We compared the effects of this two systems on patients requiring open abdominal treatment. Materials and methods: Patients with secondary peritonitis in at least two abdominal quadrants were included in this randomized study. Inclusion criteria were secondary peritonitis (ACS), abdominal compartment syndrome, and abdominal trauma combined with ACS and/or contaminated abdomen. Patients with active bleeding and pancreatitis were not included. We examined Mannheim peritonitis Index (MPI), bloodcount, PCT, amount of fluid collected, and morphological changes on the bowel. Data were collected on day 2, 4, 7, 14, 21, and 28. Primary end point was fascial closure. Examination was terminated in case of death and damage to the abdominal organs. Groups were compared using Mann Whitney U-test and chi square test. Trend evaluation was evaluated using an one way repeated measure analysis of variance. P-values below 0.05 was considered significat. Results: Thirty four patients were included between August 2010 and September 2012. There were no significant difference between two groups in MPI, age, and gender. Mean duration of treatment, WBC, CRP, and abdominal closure rate were not significantly different between groups. Suprasorb CNP System collected twice more fluid than AB-Thera and decreased PCT on significantly faster rate than AB-Thera. Four patients died (11%) and four patients developed enteric fistula (11%). Closure rate was achieved in 27 out of 34 Patients (79.5%). Closure rate was not significantly different between groups. Conclusion: The use of both systems proved to be efficient and safe. The application of well-dosed, moderate negative pressure on contaminated areas of the abdomen seems to have a lot of potential and it is worth directing greater research potential in this direction.\n Copyright © 2021 Auer, Sauseng, Delcev and Kohek.\n\nAuer-Schönbach, Thomas\n\nSauseng, Siegfried\n\n\n"
},
{
"text": "\n144580\nInvitro study of adherent mandibular osteoblast-like cells on carrier materials.\n\nTurhani, D\n\nWeissenböck, M\n\nWatzinger, E\n\nYerit, K\n\nCvikl, B\n\nEwers, R\n\nThurnher, D\n\nBeiträge in Fachzeitschriften\nISI:000230178800015\n16053876.0\n10.1016/j.ijom.2004.10.023\nNone\nAugmentation of the craniofacial region is necessary for many aesthetic and reconstructive procedures. Tissue engineering offers a new option to supplement existing treatment regimens. In this procedure, materials composed of hydroxyapatite (HA), of synthetic or natural origin, are used as scaffolds. The aim of this study was to evaluate the effects of three HA materials on cultured human osteoblasts in vitro. Explant cultures of cells from human alveolar bone were established. Human osteoblasts were cultured on the surface of HA calcified from red algae (C GRAFT/Algipore), deproteinized bovine HA (Bio-Oss) and bovine HA carrying the cell binding peptide P-15 (Pep Gen P-15). Cultured cells were evaluated with respect to cell attachment, proliferation and differentiation. Cells were cultured for 6 and 21 days under osteogenic differentiation conditions, and tissue-culture polystyrene dishes were used as control. The ability of cells to proliferate and form extracellular matrix on these scaffolds was assessed by a DNA quantification assay, protein synthesis analysis and by scanning electron microscopical examination. Osteogenic differentiation was screened by the expression of alkaline phosphatase. The osteoblastic phenotype of the cells was monitored using mRNA levels of the bone-related proteins including osteocalcin, osteopontin and collagen Type I. We found that cells cultured on C GRAFT/Algipore) and Pep Gen P-15 showed a continuous increase in DNA content and protein synthesis. Cells cultured on Bio-Oss showed a decrease in DNA content from Day 6 (P < 0.05) to Day 21 (P < 0.0001) and protein synthesis on Day 21 (P < 0.005). Alkaline phosphatase activity increased in cells grown on C GRAFT/Algipore and Pep Gen P-15 in contrast to cells grown on Bio-Oss, in which the lowest levels of activity could be observed on Day 21 (P < 0.05). Reverse transcriptase polymerase chain reaction analysis confirmed the osteoblastic phenotype of the cells grown on all three materials throughout the whole culture period. The results of our in vitro study show that the differences in metabolic activity of cells grown on HA materials are directly related to the substrate on which they are grown. They confirm the excellent properties of HA carrying the cell binding peptide P-15 and HA calcified from red algae as used in maxillofacial surgery procedures.\n\nThurnher, Dietmar\n\n\n"
},
{
"text": "\n145969\nIs the state of health of rheumatoid arthritis patients receiving adequate treatment, predictable? - Results of a survey.\n\nPuchner, R\n\nBrezinschek, HP\n\nFritz, J\n\nHerold, M\n\nMustak, M\n\nNothnagl, T\n\nPuchner, SE\n\nStudnicka-Benke, A\n\nLeeb, BF\n\nBeiträge in Fachzeitschriften\nISI:000354160600001\n25943629.0\n10.1186/s12891-015-0567-5\nPMC4427952\nA survey was conducted to evaluate whether a steady improvement in the quality of life of Rheumatoid Arthritis (RA) patients as frequently reported in clinical studies, does actually occur. The focus of this study laid on the personal perception of RA patients. How do patients who have been treated along accepted guidelines see the state of their health and their joint pain at different points in time?\n RA patients were asked to complete a questionnaire and return it to an opinion research centre. The questionnaire, which was developed by the authors, was divided into the areas: demography, symptom description and medical care, as well as the illness in a personal context. Three telephone interviews followed in monthly intervals when the patients' feelings about their illness, their every-day coping mechanisms and their social lives were rated. Intra-subject correlation and the level of agreement among patients when assessed at three different points within a two month period, was determined.\n 127 patients replied to the questionnaire. RA exerts a significant impact on a patient's daily life. Average ratings of current state of health and joint pain (answered on a 5-part scale extending from 1 (very good) to 5 (very bad)) range between 2.6 and 2.9 all three times. However, intra-subject correlation between the different assessment times, is in general quite modest. Concerning the question: "How is your join pain today?" only 14 of 127 participants express identical ratings all three times , while in one third of the participants, a difference of two digits on the 5-part scale, at least twice had to be noticed. Intra-class correlation coefficients between answers at different points are often much smaller than 0.5. Results were similar in all subgroups analysed (men vs. women; patients receiving biologics vs. those not receiving biologics; disease duration ≤3 years vs. 4 to 10 years vs. ≥11 years).\n On an individual level personal assessments of health, well-being and joint pain are nevertheless unsteady even within the timeframe of two months. This is why, even now, RA patients still cannot plan their lives as non-affected people can.\n\nBrezinsek, Hans-Peter\n\n\n"
},
{
"text": "\n146841\nDesigning a mutant CCL2-HSA chimera with high glycosaminoglycan-binding affinity and selectivity.\n\nGerlza, T\n\nWinkler, S\n\nAtlic, A\n\nZankl, C\n\nKonya, V\n\nKitic, N\n\nStrutzmann, E\n\nKnebl, K\n\nAdage, T\n\nHeinemann, A\n\nWeis, R\n\nKungl, AJ\n\nBeiträge in Fachzeitschriften\nISI:000361314400001\n25969511.0\n10.1093/protein/gzv025\nNone\nChemokines like CCL2 mediate leukocyte migration to inflammatory sites by binding to G-protein coupled receptors on the target cell as well as to glycosaminoglycans (GAGs) on the endothelium of the inflamed tissue. We have recently shown that the dominant-negative Met-CCL2 mutant Y13A/S21K/Q23R with improved GAG binding affinity is highly bio-active in several animal models of inflammatory diseases. For chronic indications, we have performed here a fusion to human serum albumin (HSA) in order to extend the serum half-life of the chemokine mutant. To compensate a potential drop in GAG-binding affinity due to steric hindrance by HSA, a series of novel CCL2 mutants was generated with additional basic amino acids which were genetically introduced at sites oriented towards the GAG ligand. From this set of mutants, the Met-CCL2 variant Y13A/N17K/S21K/Q23K/S34K exhibited high GAG-binding affinity and a similar selectivity as wild type (wt) CCL2. From a set of different HSA-chemokine chimeric constructs, the linked HSA(C34A)(Gly)4Ser-Met-CCL2(Y13A/N17K/S21K/Q23K/S34K) fusion protein was found to show the best overall GAG-binding characteristics. Molecular modeling demonstrated an energetically beneficial fold of this novel protein chimera. This was experimentally supported by GdmCl-induced unfolding studies, in which the fusion construct exhibited a well-defined secondary structure and a transition point significantly higher than both the wt and the unfused CCL2 mutant protein. Unlike the wt chemokine, the quaternary structure of the HSA-fusion protein is monomeric according to size-exclusion chromatography experiments. In competition experiments, the HSA-fusion construct displaced only two of seven unrelated chemokines from heparan sulfate, whereas the unfused CCL2 mutant protein displaced five other chemokines. The most effective concentration of the HSA-fusion protein in inhibiting CCL2-mediated monocyte attachment to endothelial cells, as detected in the flow chamber, was 8.6 µg/ml. This novel HSA-fusion protein exhibits not only high affinity but also selective displacement of chemokines from GAGs binding. HSA is therefore proposed to be a highly promising scaffold candidate for therapeutic, GAG-targeting chemokine mutants. \n © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.\n\nHeinemann, Akos\n\n\n"
},
{
"text": "\n153347\nLong-term in vivo degradation behavior and near-implant distribution of resorbed elements for magnesium alloys WZ21 and ZX50.\n\nAmerstorfer, F\n\nFischerauer, SF\n\nFischer, L\n\nEichler, J\n\nDraxler, J\n\nZitek, A\n\nMeischel, M\n\nMartinelli, E\n\nKraus, T\n\nHann, S\n\nStanzl-Tschegg, SE\n\nUggowitzer, PJ\n\nLöffler, JF\n\nWeinberg, AM\n\nProhaska, T\n\nBeiträge in Fachzeitschriften\nISI:000383292700040\n27343708.0\n10.1016/j.actbio.2016.06.025\nNone\nWe report on the long-term effects of degrading magnesium implants on bone tissue in a growing rat skeleton using continuous in vivo micro-Computed Tomography, histological staining and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Two different magnesium alloys-one rapidly degrading (ZX50) and one slowly degrading (WZ21)-were used to evaluate the bone response and distribution of released Mg and Y ions in the femur of male Sprague-Dawley rats. Regardless of whether the alloy degrades rapidly or slowly, we found that bone recovers restitutio ad integrum after complete degradation of the magnesium implant. The degradation of the Mg alloys generates a significant increase in Mg concentration in the cortical bone near the remaining implant parts, but the Mg accumulation disappears after the implant degrades completely. The degradation of the Y-containing alloy WZ21 leads to Y enrichment in adjacent bone tissues and in newly formed bone inside the medullary space. Locally high Y concentrations suggest migration not only of Y ions but also of Y-containing intermetallic particles. However, after the full degradation of the implant the Y-enrichment disappears almost completely. Hydrogen gas formation and ion release during implant degradation did not harm bone regeneration in our samples.\n Magnesium is generally considered to be one of the most attractive base materials for biodegradable implants, and many magnesium alloys have been optimized to adjust implant degradation. Delayed degradation, however, generates prolonged presence in the organism with the risk of foreign body reactions. While most studies so far have only ranged from several weeks up to 12months, the present study provides data for complete implant degradation and bone regeneration until 24months, for two magnesium alloys (ZX50, WZ21) with different degradation characteristics. μCT monitoring, histological staining and LA-ICP-MS illustrate the distribution of the elements in the neighboring bony tissues during implant degradation, and reveal in particular high concentrations of the rare-earth element Yttrium.\n Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.\n\nAmerstorfer, Florian Ludwig\n\nFischerauer, Stefan Franz\n\nKraus, Tanja\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n168313\nIndexing of grazing-incidence X-ray diffraction patterns: the case of fibre-textured thin films.\n\nSimbrunner, J\n\nSimbrunner, C\n\nSchrode, B\n\nRöthel, C\n\nBedoya-Martinez, N\n\nSalzmann, I\n\nResel, R\n\nBeiträge in Fachzeitschriften\nISI:000437746600008\n29978847.0\n10.1107/S2053273318006629\nPMC6038360\nCrystal structure solutions from thin films are often performed by grazing-incidence X-ray diffraction (GIXD) experiments. In particular, on isotropic substrates the thin film crystallites grow in a fibre texture showing a well defined crystallographic plane oriented parallel to the substrate surface with random in-plane order of the microcrystallites forming the film. In the present work, analytical mathematical expressions are derived for indexing experimental diffraction patterns, a highly challenging task which hitherto mainly relied on trial-and-error approaches. The six lattice constants a, b, c, α, β and γ of the crystallographic unit cell are thereby determined, as well as the rotation parameters due to the unknown preferred orientation of the crystals with respect to the substrate surface. The mathematical analysis exploits a combination of GIXD data and information acquired by the specular X-ray diffraction. The presence of a sole specular diffraction peak series reveals fibre-textured growth with a crystallographic plane parallel to the substrate, which allows establishment of the Miller indices u, v and w as the rotation parameters. Mathematical expressions are derived which reduce the system of unknown parameters from the three- to the two-dimensional space. Thus, in the first part of the indexing routine, the integers u and v as well as the Laue indices h and k of the experimentally observed diffraction peaks are assigned by systematically varying the integer variables, and by calculating the three lattice parameters a, b and γ. Because of the symmetry of the derived equations, determining the missing parameters then becomes feasible: (i) w of the surface parallel plane, (ii) the Laue indices l of the diffraction peak and (iii) analogously the lattice constants c, α and ß. In a subsequent step, the reduced unit-cell geometry can be identified. Finally, the methodology is demonstrated by application to an example, indexing the diffraction pattern of a thin film of the organic semiconductor pentacenequinone grown on the (0001) surface of highly oriented pyrolytic graphite. The preferred orientation of the crystallites, the lattice constants of the triclinic unit cell and finally, by molecular modelling, the full crystal structure solution of the as-yet-unknown polymorph of pentacenequinone are determined.\n open access.\n\nSimbrunner, Josef\n\n\n"
},
{
"text": "\n174185\nAssociation of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects.\n\nMishra, A\n\nChauhan, G\n\nViolleau, MH\n\nVojinovic, D\n\nJian, X\n\nBis, JC\n\nLi, S\n\nSaba, Y\n\nGrenier-Boley, B\n\nYang, Q\n\nBartz, TM\n\nHofer, E\n\nSoumaré, A\n\nPeng, F\n\nDuperron, MG\n\nFoglio, M\n\nMosley, TH\n\nSchmidt, R\n\nPsaty, BM\n\nLauner, LJ\n\nBoerwinkle, E\n\nZhu, Y\n\nMazoyer, B\n\nLathrop, M\n\nBellenguez, C\n\nVan Duijn, CM\n\nIkram, MA\n\nSchmidt, H\n\nLongstreth, WT\n\nFornage, M\n\nSeshadri, S\n\nJoutel, A\n\nTzourio, C\n\nDebette, S\n\nBeiträge in Fachzeitschriften\nISI:000472805000019\n30859180.0\n10.1093/brain/awz024\nPMC6439324\nWe report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, nWESextremes = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (nWES = 2, 68, nWESextremes = 956) and genome-wide genotypes (nGW = 9924, nGWextremes = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (Pdiscovery = 8.21 × 10-5, Preplication = 5.25 × 10-3, Pcombined = 4.72 × 10-5) and of NOTCH3 using gene-based tests (Pdiscovery = 1.61 × 10-2, Preplication = 3.99 × 10-2, Pcombined = 5.31 × 10-3). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease.\n © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.\n\nHofer, Edith\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n178447\nCharacterizing neonatal vitamin D deficiency in the modern era: a maternal-neonatal birth cohort from Southern Europe.\n\nKarras, SN\n\nKoufakis, T\n\nAntonopoulou, V\n\nGoulis, DG\n\nAnnweiler, C\n\nPilz, S\n\nBili, H\n\nNaughton, DP\n\nShah, I\n\nHarizopoulou, V\n\nZebekakis, P\n\nBais, A\n\nKotsa, K\n\nBeiträge in Fachzeitschriften\nISI:000526115200015\n31783152.0\n10.1016/j.jsbmb.2019.105555\nNone\nAbsence of adequate maternal vitamin D supplementation and decreased maternal ultraviolet exposure during pregnancy are key determinants for the manifestation of neonatal hypovitaminosis D at birth. These parameters may vary, according to country-specific dietary patterns, health policies and sunshine exposure. We aimed to investigate differences in calcium metabolism and anthropometric profiles according to neonatal vitamin D status at birth, in a sunny region of Northern Greece. A secondary aim was to identify maternal parameters as risk factors for developing neonatal vitamin D deficiency at birth. A total of 129 mother-neonate pairs were included in the study and classified into three groups, according to neonatal 25-hydroxy-D [25(OH)D)] concentrations at birth [deficiency (<30 nmol/l), insufficiency (30-50 nmol/l) and sufficiency (>50 nmol/l)]. Neonatal biochemical and anthropometric profiles and maternal demographic, social, dietary and biochemical profiles were comparatively evaluated between the three groups. Univariate and multivariate logistic regression was performed to identify independent associations of maternal factors with neonatal vitamin D status. Vitamin D deficient-neonates manifested higher parathyroid hormone (7.20 ± 2.60 vs 5.50 ± 1.50 pg/ml, p = 0.01) and lower corrected calcium (10.70 ± 0.70 vs 11.30 ± 1.30 mg/dl, p = 0.02) concentrations compared with vitamin D-insufficient neonates. Mothers of vitamin D deficient and insufficient neonates had a lower total of 25(OH)D (31.7 ± 19.2 and 36.5 ± 22.3 vs 53.3 ± 39.0 nmol/l, p < 0.01) and 25(OH)D3 (27.4 ± 17.5 and 33.3 ± 19.9 vs 47.3 ± 36.7 nmol/l, p < 0.01 and p = 0.04, respectively) concentrations respectively, compared with those of vitamin D-sufficient neonates. Maternal use of alcohol during pregnancy was associated with a 5.57-fold higher risk for neonatal vitamin D deficiency at birth (OR 5.57, 95% CI1.17-26.56, p = 0.03). Newborns with vitamin D deficiency presented a 6.89-fold higher risk of having been given birth by vitamin D deficient mothers (OR 6.89, 95% CI 3.09-15.38, p < 0.01). In conclusion, neonatal vitamin D deficiency is associated with maternal 25(OH)D concentrations at birth and maternal alcohol use. Further studies are required to replicate these findings in other regions and populations.\n Copyright © 2019. Published by Elsevier Ltd.\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n187053\nSurvival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.\n\nBeyer, J\n\nCollette, L\n\nSauvé, N\n\nDaugaard, G\n\nFeldman, DR\n\nTandstad, T\n\nTryakin, A\n\nStahl, O\n\nGonzalez-Billalabeitia, E\n\nDe Giorgi, U\n\nCuline, S\n\nde Wit, R\n\nHansen, AR\n\nBebek, M\n\nTerbuch, A\n\nAlbany, C\n\nHentrich, M\n\nGietema, JA\n\nNegaard, H\n\nHuddart, RA\n\nLorch, A\n\nCafferty, FH\n\nHeng, DYC\n\nSweeney, CJ\n\nWinquist, E\n\nChovanec, M\n\nFankhauser, C\n\nStark, D\n\nGrimison, P\n\nNecchi, A\n\nTran, B\n\nHeidenreich, A\n\nShamash, J\n\nSternberg, CN\n\nVaughn, DJ\n\nDuran, I\n\nBokemeyer, C\n\nPatrikidou, A\n\nCathomas, R\n\nAssele, S\n\nGillessen, S\n\nInternational Germ Cell Cancer Classification Update Consortium\n\nBeiträge in Fachzeitschriften\nISI:000655611500005\n33729863.0\n10.1200/JCO.20.03292\nNone\nThe classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.\n Data on 2, 51 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.\n Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.\n PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.\n\nTerbuch, Angelika\n\n\n"
},
{
"text": "\n2022\nPost-traumatic dynamic change of carboxyterminal propeptide of type I procollagen, alkaline phosphatase and its isoenzymes as predictors for enhanced osteogenesis in patients with severe head injury.\n\nWildburger, R\n\nZarkovic, N\n\nDobnig, H\n\nPetek, W\n\nHofer, HP\n\nBeiträge in Fachzeitschriften\nISI:A1994PC72200005\n7800934.0\n10.1007/BF02576386\nNone\nPatients suffering from severe head injury and fractures of long bones or large joints often show enhanced osteogenesis, with hypertrophic callus formation and/or heterotopic ossifications. The advantage of this phenomenon is early consolidation of the fractures. An extreme disadvantage is extensive periarticular calcification, resulting in complete ankylosis of the affected joint. In spite of numerous efforts aimed at clarifying the way in which severe head injury can influence osteogenesis at a distant site, this phenomenon is still not understood. The process, once started, seems irreversible, but if diagnosed in time, could be prevented with non-steroid anti-inflammatory drugs that inhibit development of heterotopic ossifications. The major prerequisite for testing this possibility is to define parameters of an early diagnosis of enhanced osteogenesis. Thus, the aim of this study was to test whether serum values of some parameters related to bone regeneration could allow an early prediction of enhanced ossification following bone fracture in patients with severe head injury. Samples of sera were obtained from three groups of injured patients: fractures of long bones or large joints only (n = 6), severe head injury only (n = 8), severe head injury and fractures of long bones and large joints (n = 7) and from a group of apparently healthy volunteers (n = 10). The values for alkaline phosphatase (ALP), the bone isoenzyme, and the carboxy terminal propeptide of type I procollagen (PICP) were significantly higher (5-20 times as high) in patients with severe head injury and bone or joint fractures than in any other group. Significantly increased concentrations of PICP were already found in the 1st week after injury, and those of ALP and of the bone isoenzyme increased during the 2nd week after injury. Results show that these parameters are helpful for an early diagnosis of enhanced osteogenesis and heterotopic ossifications in patients with severe head injury and bone fractures. Further studies are necessary to verify these findings, while analysis of reasons for the specific patterns of dynamic change of these parameters could lead to better understanding of the mechanisms underlying the uncontrolled bone formation.\n\nHofer, Herwig\n\n\n"
}
]
}