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"text": "\n128143\nFractures of the proximal humerus\n\nSzyszkowitz, R\n\nSchippinger, G\n\nBeiträge in Fachzeitschriften\nISI:000081266300002\n10420821.0\n10.1007/s001130050430\nNone\nProximal humeral fractures are common particularly in the elderly. The decision of the optimal treatment is dependent on many factors. On the one hand the biological age of the patient and the bone structure plays a key-role, on the other hand the living conditions and individual needs are of importance. Most fractures with minimal displacement respond satisfactorily to simple conservative treatment including short sling immobilisation and functional aftertreatment under supervision of the physiotherapist. Most recently there is a trend towards more aggressive surgical intervention with percutaneous insertion of cannulated screws also in the slightly displaced fracture situation. This protocol allows for earlier functional and less painful aftertreatment, less risk of displacement of the fracture fragments and better outcome. In severely unstable fractures with marked displacement of the fragments an operative stabilisation is advocated by most surgeons. Again there is a trend from plating towards cannulated screw fixation combined with tension absorbing (resorbable) sutures. In special cases which are described in detail a minimal invasive percutaneous screw technique with less stripping of bone and therefore preservation of the crucial blood supply of the humeral head is recommended. Instead of percutaneous pinning using K-wires only, cannulated screws are inserted today. Plating of proximal humerus joint fractures is the exception in our days, only the subcapital unstable fracture of the elderly would be an indication. LC-condylar plating seems to yield better stability than the conventional T-plate-system. In the most severe fractures of the proximal humerus (4-segment-fractures and dislocation fractures according to Neer, respectively C-2- and C-3-fractures according to the AO-classification) there is still controversy on the best management. Most authors prefer hemiarthroplasty in this situation whereas the other group of orthopaedic surgeons try open reduction and internal fixation particularly in the younger individuals. This stabilisation provides the orthopaedic surgeons with a formidable challenge and requires a lot of experience in this field. Also the understanding of the fracture morphology is needed for optimal results. In spite of good stabilisation techniques often partial or total humeral head necrosis occurs in the most severe fractures. Surprisingly enough results with reasonable function can be obtained even with partial avascular necrosis of the humeral head. A crucial part of the management is team work with the physiotherapist and an individual program for each fracture situation, depending on the stability of the fixation. Close contact between these two professions is of utmost importance. Finally it can be stated that the management of proximal humeral fractures is fairly standardised but it is always dependent on the experience and resources of the attending surgeon and must be tailored to the individual needs of the patient.\n\n\n"
},
{
"text": "\n831\nEffect of oxidative stress by iron on 4-hydroxynonenal formation and proliferative activity in hepatomas of different degrees of differentiation.\n\nHammer, A\n\nFerro, M\n\nTillian, HM\n\nTatzber, F\n\nZollner, H\n\nSchauenstein, E\n\nSchaur, RJ\n\nBeiträge in Fachzeitschriften\nISI:A1997WZ43700004\n9165294.0\n10.1016/S0891-5849(96)00630-2\nNone\nIt has been shown previously that oxidative stress by ferrous iron in vitro leads to an inhibition of proliferation of murine ascites tumour cells in vivo. This effect is associated with increased lipid peroxidation in terms of formation of the highly reactive aldehyde 4-hydroxynonenal (HNE), which has been shown to inhibit the proliferation of numerous tumours and to induce differentiation. It was the purpose of this article to study the occurrence and metabolism of HNE and its inducibility by oxidative stress in hepatomas of different degrees of differentiation to find further evidence for a possible role of HNE in proliferation and/or differentiation, because it is known that in hepatoma cells with a very low degree of differentiation basal lipid peroxidation is hardly detectable, while in normal hepatocytes the basal level of thiobarbituric acid reactive substances (TBArS) is rather high. MH1C1 hepatoma cells and Yoshida AH-130 hepatoma cells were chosen as highly differentiated and poorly differentiated tumour cells, respectively, and rat hepatocytes served as a control for normal liver phenotype. Ferrous histidinate (Fe/His) did not have a cytotoxic effect on Yoshida and MH1C1 cells, as measured by the LDH release test. In cell culture studies Fe/His revealed a dose dependent inhibition of the proliferation of Yoshida cells. The incorporation of 3H-thymidine into DNA of these cells was also inhibited by Fe/His in a dose-dependent manner, while the precursor uptake into the cytoplasm was unaffected. The basal levels of HNE were in the order: hepatocytes > MH1C1 cells > Yoshida cells. Both hepatocytes and Yoshida cells responded to the presence of Fe/His with increased formation of TBArS. Compared with hepatocytes the response of the Yoshida cells was greatly reduced. The response of cells to Fe/His with respect to HNE formation was decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells, but in this case the differences were not very pronounced. The metabolic capacity of the cells to consume HNE was also decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells. In this case the differences were very pronounced. These findings support the view that Yoshida cells with a low degree of differentiation and a low basal level of HNE are released from an inhibitory effect of HNE operative in hepatocytes and that HNE is causally involved in the iron induced inhibition of proliferation of poorly differentiated hepatoma cells.\n\nHammer, Astrid\n\nTatzber, Franz\n\n\n"
},
{
"text": "\n118561\nLaparoscopic treatment of acute small bowel obstruction(*)\n\nUranues, S\n\nTomasch, G\n\nNagele-Moser, D\n\nBeiträge in Fachzeitschriften\nISI:000301103800006\nNone\n10.1007/s10353-012-0075-x\nNone\nBACKGROUND: Symptoms of obstruction in the intestinal tract involve the small intestine in three quarters of cases and the large intestine in one-quarter. The most common causes of an acute small intestinal obstruction are postoperative adhesions (64.8%) and strangulated hernias (14.8%). The overall incidence of postoperative small bowel obstruction is 4.6%. Because it offers a conservative and targeted means of removing the obstruction, laparoscopy is increasingly used for acute small bowel obstruction. With proper selection of patients, the success rate is very high. This work presents the selection criteria, technique and results for a three-year period. METHODS: Twenty-one patients, 13 men and 8 women aged 28 to 69 years, underwent surgery between January 2008 and December 2010. Selection criteria for a laparoscopic procedure were anesthesia risk of not more than ASA 3, diameter of the dilatated loop of small intestine of not more than 5 cm, radiological image of a change in caliber as an indication of a focal passage disorder, exclusion of paralytic ileus, and no history of diffuse peritonitis. The patients underwent surgery in general anesthesia. The approach for the first trocar was umbilical in 18 cases and in the right or left flank in three cases, but always with open technique. Three trocars were always used. RESULTS: In 7 patients, there was an isolated band from a previous operation, usually an appendectomy; in 5 cases there were postoperative adhesions and a band. Three patients had a volvulus and in one of them, a 20 cm segment of the small intestine was already gangrenous. Two patients had an incarcerated hernia, one inguinal and one Bochdalek. Two patients had a stenosing tumor in the terminal ileum, one of which was a carcinoid and the other, the first manifestation of a lymphoma. One patient had an endometriosis focus as stenosis focus and another had a massively inflamed Meckel's diverticulum that obstructed passage in the small intestine. Two patients - the volvulus with small intestinal gangrene and the Bochdalek hernia - required conversion to open technique. One patient with diffuse adhesions and a band had to undergo open surgery 10 days later. There was no case of an intraoperative accidental intestinal injury. All the patients who underwent laparoscopy were discharged within a week. Hospitalization was significantly longer for the converted patients. The patient with the Boachdalek hernia died after 26 days of irreversible cardiopulmonary failure. CONCLUSIONS: With strict selection, laparoscopic treatment of small intestinal obstruction is a valuable option in visceral acute surgery. Patients with an isolated focal obstruction seem to benefit from laparoscopic surgery on the basis of reduced perioperative morbidity and short hospitalization.\n\nTomasch, Gordana\n\nUranüs, Selman\n\n\n"
},
{
"text": "\n129724\nIncreasing physical activity for the treatment of hypertension: a systematic review and meta-analysis.\n\nSemlitsch, T\n\nJeitler, K\n\nHemkens, LG\n\nHorvath, K\n\nNagele, E\n\nSchuermann, C\n\nPignitter, N\n\nHerrmann, KH\n\nWaffenschmidt, S\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000324796600008\n23812856.0\n10.1007/s40279-013-0065-6\nNone\nLow physical activity has been identified as a major risk factor for cardiovascular disease. Medical societies therefore recommend increased physical activity be part of any antihypertensive therapy.\n Focusing on patient-relevant outcomes such as mortality and cardiovascular events, this review was conducted to assess the long-term effects of interventions aiming at increasing physical activity in comparison with no such interventions on adult patients with essential hypertension.\n We searched for high-quality systematic reviews in MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (Cochrane Reviews), Database of Abstracts of Reviews of Effects (Other Reviews) and Health Technology Assessment Database (Technology Assessments) published between 1997 and February 2009 and for randomized controlled trials (RCTs) in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (Clinical Trials) published before September 2012. Additional studies were identified by hand searching reference lists of reviews.\n RCTs with at least 24 weeks' follow-up that evaluated the effect of increased physical activity on the blood pressure of adults with essential hypertension were included in our review. Primary outcomes were all-cause mortality, cardiovascular morbidity and mortality, end-stage renal disease, quality of life and adverse events.\n When appropriate, we used random effects meta-analyses to determine mean difference with 95 % confidence intervals for each endpoint. All data were analysed using the Review Manager software version 5.0.24 from the Cochrane Collaboration.\n None of the included nine trials, covering 891 patients with hypertension, provided sufficient data on patient-relevant outcomes such as mortality, cardiovascular events or injuries related to physical activity. Information on changes in systolic and diastolic blood pressure was provided for all included trials. The majority of the included RCTs reported that increased physical activity led to a decrease in systolic and diastolic blood pressure of 5-10 and 1-6 mmHg, respectively, but due to marked heterogeneity in the meta-analyses both for systolic and diastolic blood pressure (I² = 70.0 and 73.0 %), no effect estimates were provided.\n About 50 % of the included trials were small, evaluating at most 20 participants per study group, and more than twothirds were deemed to have a high risk of bias.\n Although a decrease in blood pressure is shown to be a consequence of increased physical activity, RCTs of appropriate study size and quality that examine potential patient-relevant benefits or harms still need to be conducted to evaluate whether physical activity really improves the health of patients with essential hypertension.\n\nHorvath, Karl\n\nJeitler, Klaus\n\nNagele, Eva Helene\n\nPosch, Nicole\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n175671\nAnti-inflammatory and antiproliferative compounds from Sphaeranthus africanus.\n\nTran, HT\n\nGao, X\n\nKretschmer, N\n\nPferschy-Wenzig, EM\n\nRaab, P\n\nPirker, T\n\nTemml, V\n\nSchuster, D\n\nKunert, O\n\nHuynh, L\n\nBauer, R\n\nBeiträge in Fachzeitschriften\nISI:000500559500020\n31136898.0\n10.1016/j.phymed.2019.152951\nNone\nSphaeranthus africanus has been used in traditional Vietnamese medicine to treat sore throat, and to relieve pain and swelling. However, the anti-inflammatory activity of this plant had not yet been investigated. Previously, we isolated five carvotacetones (1-5) from this plant that displayed cytotoxicity against several cancer cell lines.\n The objective of this study was to isolate further constituents from S. africanus and to investigate the anti-inflammatory activity of all constituents. Furthermore, the anti-proliferative activity of the newly isolated compounds was evaluated.\n Compounds were isolated from the upper parts of S. africanus by chromatographic methods. Structures were determined using spectroscopic techniques, like NMR and MS. All nine compounds isolated from S. africanus were evaluated for inhibitory activity against COX-1 and COX-2 isoenzymes in-vitro, COX-2 mRNA expression and influence on NO production. The anti-proliferative activities of newly isolated compounds (6-9) were evaluated by XTT viability assay with four cancer cell lines, namely CCRF-CEM, MDA-MB-231, HCT-116, and U-251 cells.\n Two diastereomeric carvotacetones (3-angeloyloxy-5-[2″S, ″R-dihydroxy-2″-methyl-butanoyloxy]-7-hydroxycarvotacetone (6) and 3-angeloyloxy-5-[2″R, ″R-dihydroxy-2″-methyl-butanoyloxy]-7-hydroxycarvotacetone (7), asperglaucide (8) and chrysoplenol D (9) were isolated from S. africanus. COX-1 and COX-2 assays of compounds 1-9 revealed that compounds 1 and 2 possess potent and selective COX-2 inhibitory activity with IC50 values of 3.6 and 0.5 μM, respectively. COX-2 gene expression assay showed that some carvotacetones exhibited inhibitory effects on COX-2 gene expression in THP-1 macrophages. Compound 4 is the most active compound inhibiting the synthesis of COX-2 by 55% at 2.06 μM. In the iNOS assay, all seven carvotacetones inhibited NO production in BV2 and RAW cell lines with IC50 values ranging from 0.2 to 2.9 μM. Compound 4 showed potent inhibitory activity with IC50 values of 0.2 μM in both BV2 and RAW cell lines. Molecular docking studies revealed the binding orientations of 1 and 2 in the active sites of COX-2. XTT assay of the newly isolated compounds revealed that the two isomeric carvotacetones (6-7) exhibited considerable anti-proliferative activity against four cancer cell lines (CCRF-CEM, MDA-MB-231, HCT-116, U-251) with IC50 values ranging from 1.23 to 8 μM.\n For the first-time, the diastereomeric carvotacetones (6-7) were isolated as separate compounds, and their anti-proliferative activity was determined. Selective COX-2 inhibitory, COX-2 mRNA expression and NO production inhibitory activities by some of the major constituents of S. africanus supports the traditional medical application of this plant for the treatment of inflammation-related disorders.\n Copyright © 2019 Elsevier GmbH. All rights reserved.\n\n\n"
},
{
"text": "\n182405\nDifferential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review.\n\nSakellariou, G\n\nScirè, CA\n\nAdinolfi, A\n\nBatticciotto, A\n\nBortoluzzi, A\n\nDelle Sedie, A\n\nDe Lucia, O\n\nDejaco, C\n\nEpis, OM\n\nFilippucci, E\n\nIdolazzi, L\n\nPicchianti Diamanti, A\n\nZabotti, A\n\nIagnocco, A\n\nFilippou, G\n\nBeiträge in Fachzeitschriften\nISI:000536111500001\n32457913.0\n10.3389/fmed.2020.00141\nPMC7221062\nBackground: Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. Methods: In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. Results: For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Conclusions: Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.\n Copyright © 2020 Sakellariou, Scirè, Adinolfi, Batticciotto, Bortoluzzi, Delle Sedie, De Lucia, Dejaco, Epis, Filippucci, Idolazzi, Picchianti Diamanti, Zabotti, Iagnocco and Filippou.\n\nDejaco, Christian\n\n\n"
},
{
"text": "\n4894\nIn-patient comparison of immediately loaded and non-loaded implants within 6 months.\n\nLorenzoni, M\n\nPertl, C\n\nZhang, K\n\nWegscheider, WA\n\nBeiträge in Fachzeitschriften\nISI:000183419800004\n12755777.0\n10.1034%2Fj.1600-0501.2003.140304.x\nNone\nAccording to the Brånemark protocol, a stress-free healing period is one of the most emphasised requirements for implant integration. Recent studies have encouraged a progressive shortening of the healing period and immediate loading has been proposed for the edentulous mandible. This prospective study evaluated the clinical outcomes of 14 immediately loaded FRIALIT-2(R) implants compared with 28 non-loaded controls in an in-patient study. The results were based on clinical stability and on changes of bone level from implant placement to abutment connection 6 months after insertion. In the course of our investigation, seven patients with edentulous mandibles have been treated with 43 implants following an immediate-loading protocol. Six FRIALIT-2(R) implants were placed in the interforaminal region located at positions 34, 33, 32, 42, 43, 44. Bone level in relation to implant margin was measured and recorded. In order to obtain an in-patient comparison of immediately loaded and non-loaded implants, the ones at 33 and 43 were chosen to be immediately loaded by a Dolder-bar retained overdenture. The implants in position 32, 34, 42 and 44 were covered and left to heal. After a healing period of 6 months, second stage surgery was carried out. The clinical criteria to be checked at this point were survival, Periotest values and marginal bone level at the loaded and non-loaded implants. The mean Periotest value was -2.7 for the loaded and -5.6 for the non-loaded implants. The Mann-Whitney U-test showed that the difference was highly significant (P < 0.001). The mean bone level changes at prosthetic delivery were 0.9 mm resorption for the loaded implants and 0.33 mm for non-loaded implants. The difference was highly significant (P < 0.001). No implant failures were observed up to the prosthetic restoration 6 months post insertion. The results of this investigation allowed for direct comparison of implant survival and clinical results between immediately loaded implants and standard implants. Clinical bone changes at the 6-month evaluation demonstrated significantly higher crestal resorption around loaded implants. This fact was confirmed by higher median Periotest values (-3 vs. -6) of immediately loaded implants. According to the outcome of this study, immediate loading of two interforaminal implants with a Dolder-bar resulted in an intimate bone apposition comparable with implants with submerged healing. Nevertheless, the coronal bone level as well as clinical stability (PTV) were significantly lower in the case of the immediately loaded implants. Future studies will be necessary to evaluate marginal bone resorption, Periotest values and clinical success rates of mandibular immediately loaded implants in the long-term.\n\nLorenzoni, Martin\n\nWegscheider, Walther\n\n\n"
},
{
"text": "\n90430\nLarge scale association analysis of novel genetic loci for coronary artery disease.\n\nAmouyel, P\n\nArveiler, D\n\nBoekholdt, SM\n\nBraund, P\n\nBruse, P\n\nBumpstead, SJ\n\nBugert, P\n\nCambien, F\n\nDanesh, J\n\nDeloukas, P\n\nDoering, A\n\nDucimetiere, P\n\nDunn, RM\n\nEl Mokhtari, NE\n\nErdmann, J\n\nEvans, A\n\nEwels, P\n\nFerrieres, J\n\nFischer, M\n\nFrossard, P\n\nGarner, S\n\nGieger, C\n\nGohri, MJR\n\nGoodall, AH\n\nGrosshennig, A\n\nHall, A\n\nHardwick, R\n\nHaukijarvi, A\n\nHengstenberg, C\n\nIllig, T\n\nKarvanen, J\n\nKastelein, J\n\nKee, F\n\nKhaw, KT\n\nKluter, H\n\nKonig, IR\n\nKuulasmaa, K\n\nLaiho, P\n\nLuc, G\n\nMarz, W\n\nMcGinnis, R\n\nMcLaren, W\n\nMeisinger, C\n\nMorrison, C\n\nOu, X\n\nOuwehand, WH\n\nPreuss, M\n\nProust, C\n\nRavindrarajah, R\n\nRenner, W\n\nRice, K\n\nRuidavets, JB\n\nSaleheen, D\n\nSalomaa, V\n\nSamani, NJ\n\nSandhu, MS\n\nSchafer, AS\n\nScholz, M\n\nSchreiber, S\n\nSchunkert, H\n\nSilander, K\n\nSingh, R\n\nSoranzo, N\n\nStark, K\n\nStegmayr, B\n\nStephens, J\n\nThompson, J\n\nTiret, L\n\nTrip, MD\n\nvan der Schoot, E\n\nVirtamo, J\n\nWareham, NJ\n\nWichmann, HE\n\nWiklund, PG\n\nWright, B\n\nZiegler, A\n\nZwaginga, JJ\n\nBeiträge in Fachzeitschriften\nISI:000265230700027\n19164808.0\n10.1161/ATVBAHA.108.181388\nPMC3315048\nBackground-Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. Methods and Results-We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81x10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44x10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02x10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34x10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P = 0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86x10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. ConclusionsThe findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations. (Arterioscler Thromb Vasc Biol. 2009; 29: 774-780.)\n\nMärz, Winfried\n\nRenner, Wilfried\n\n\n"
},
{
"text": "\n73646\nC677T single nucleotide polymorphisms of the human methylene tetrahydrofolate reductase and specific identification : a novel strategy using two-color cross-correlation fluorescence spectroscopy.\n\nFöldes-Papp, Z\n\nKinjo, M\n\nSaito, K\n\nKii, H\n\nTakagi, T\n\nTamura, M\n\nCosta, JM\n\nBirch-Hirschfeld, E\n\nDemel, U\n\nThyberg, P\n\nTilz, GP\n\nBeiträge in Fachzeitschriften\nNone\n14580229.0\nNone\nNone\nBACKGROUND: A methylene tetrahydrofolate reductase (MTHFR) deficiency at site C677T renders the enzyme thermolabile and consequently represents a risk factor for vascular disease, neural tube defects, preeclampsia, and thrombosis. Highly specific identification techniques for genotyping are mandatory to give guidance for the diagnosis and monitoring of this deficiency. METHODS: A new approach for performing genotyping has been introduced with the identification of single nucleotide polymorphisms of the human MTHFR. It is based on PCR followed by two-color cross-correlation fluorescence spectroscopy (FCS). Experiments were carried out with green- and red-tagged allele-specific primers, which were fully compatible with the two-color fluorescence cross-correlation setup at 488 nm and 633 nm excitation wavelengths. RESULTS: The measured data of the amplification mixes (tubes) were normalized as the maximum correlation amplitude of each tube. Correlated and uncorrelated data were optically separated in the amplification mixes by their characteristic correlation times, which significantly differed from each other. The correlated data were generated in the presence of the proper mutated genotype template, whereas uncorrelated data were due to the absence of the proper genotype template. Furthermore, the specific association of the two-color fluorescence correlated signals with the target DNA was experimentally proven. Using this novel two-color cross-correlation approach, the MTHFR genotypes, which were determined in 21 clinical samples, showed concordance with methods involving a PCR-based assay with hexachloro-6-carboxy-fluorescein (HEX)- and 6-carboxy-fluorescein (FAM)-tagged allele-specific primers and a subsequent separation step with capillary electrophoresis, yet are simpler to perform. There was no evidence of a central trend of false-positive or false-negative results. We demonstrated how the novel, ultrasensitive typing system could be applied to studies where researchers are trying to perfect their assays and are often working with the unknown, or application to problematic assays in a clinical environment for those involved in molecular diagnosis. CONCLUSIONS: We present an alternative method to those commonly used in genotyping. Two-color cross-correlation FCS allows the detection of the fluorescence signals specifically associated with the heterozygous mutated, the homozygous mutated, and normal individuals, as exemplified in this study. The presence of nonspecific amplification products, which interfere with subsequent DNA analysis, could therefore highlight the need for two-color cross-correlation FCS as a means of discriminating between specific association of the fluorescence signals with the target DNA and DNA not related to the target.\n\nDemel, Ulrike\n\n\n"
},
{
"text": "\n117876\nDelineation of the vitreous and posterior hyaloid using bromophenol blue.\n\nHaritoglou, C\n\nStrauss, R\n\nPriglinger, SG\n\nKreutzer, T\n\nKampik, A\n\nBeiträge in Fachzeitschriften\nISI:000253460800019\n18301040.0\n10.1097/IAE.0b013e31814fb0ff\nNone\nPurpose: To describe visualization of the vitreous and the posterior hyaloid membrane using bromophenol blue during vitrectomy for macular hole and retinal detachment. Patients and Methods: Six patients with macular holes and four with retinal detachments were included in the study. Before and after surgery, complete clinical examination, including funduscopy and measurements of best-corrected visual acuity and intraocular pressure, was performed. Additional functional tests, such as fluorescein angiography, optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Jena, Germany, Germany), Goldmann perimetry, and multifocal electroretinography as well as photography of the posterior pole, were performed for macular hole patients. Bromophenol blue was used in concentrations of 0.2%. During macular hole surgery, the dye was injected into the air-filled globe, while during surgery for retinal detachment, the globe was partially filled with perfluorocarbon before dye injection after induction of a posterior vitreous detachment to stain the vitreous peripherally. Results: Bromophenol blue provided sufficient staining of the attached posterior hyaloid membrane and vitreous remnants in the periphery. This was especially helpful for patients in whom a posterior vitreous detachment could not be induced mechanically by suction using the vitrectomy probe alone, as seen in three of six interventions for a macular hole in this series. In addition, staining of the vitreous or vitreous remnants in the periphery and at the vitreous base was seen in all patients and helped to completely remove the vitreous in a controlled fashion. After macular hole surgery, increase of visual acuity from 20/100 (mean) to 20/40 was seen during follow-up up to 6 months. In one case, the hole persisted and required a second operation. Finally, closure of the hole was achieved in all patients. After retinal detachment surgery, reattachment was achieved in all cases. No dye-related adverse events were seen during follow-up as shown by the functional tests (visual acuity measurement, electroretinography, and perimetry) applied. Conclusion: Delineation of the vitreous and the posterior hyaloid using bromophenol blue staining greatly facilitates vitreoretinal procedures. Bromophenol blue appeared to be a very helpful and safe tool to visualize the posterior hyaloid membrane in macular hole surgery and assured its complete separation from the retinal surface. The dye also helped to remove vitreous at the vitreous base during retinal detachment surgery. Therefore, bromophenol blue appears as a very good alternative to triamcinolone, which has been used for this purpose, because the dye has no pharmacological properties and no side effects are likely to occur such as cataract formation and increase in intraocular pressure. Further studies including larger numbers of patients are mandatory.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n127539\nOverlap Between Common Genetic Polymorphisms Underpinning Kidney Traits and Cardiovascular Disease Phenotypes: The CKDGen Consortium.\n\nOlden, M\n\nTeumer, A\n\nBochud, M\n\nPattaro, C\n\nKöttgen, A\n\nTurner, ST\n\nRettig, R\n\nChen, MH\n\nDehghan, A\n\nBastardot, F\n\nSchmidt, R\n\nVollenweider, P\n\nSchunkert, H\n\nReilly, MP\n\nFornage, M\n\nLauner, LJ\n\nVerwoert, GC\n\nMitchell, GF\n\nBis, JC\n\nO'Donnell, CJ\n\nCheng, CY\n\nSim, X\n\nSiscovick, DS\n\nCoresh, J\n\nKao, WH\n\nFox, CS\n\nO'Seaghdha, CM\n\nAortaGen, CARDIoGRAM, CHARGE Eye, CHARGE IMT, ICBP, NeuroCHARGE, and CKDGen Consortia\n\nBeiträge in Fachzeitschriften\nISI:000318999200009\n23474010.0\n10.1053/j.ajkd.2012.12.024\nPMC3660426\nBackground: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. Study Design: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5 x 10(-4) (0.05/325 tests). Setting & Participants: Vascular outcomes were analyzed in participants from the AortaGen (20, 34), CARDIoGRAM (86, 95), CHARGE Eye (15, 58), CHARGE IMT (31, 81), ICBP (69, 95), and NeuroCHARGE (12, 85) consortia. Tests for kidney outcomes were conducted in up to 67, 93 participants from the CKDGen consortium. Predictor: We used 19 kidney SNPs and 64 vascular SNPs. Outcomes & Measurements: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. Results: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 x 10(-10)) and diastolic (P = 1.6 x 10(-14)) blood pressure and coronary artery disease (P = 2.2 x 10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 x 10(-07) and P = 7.05 x 10(-08)). Limitations: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. Conclusions: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself. (c) 2013 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n152198\nAzacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications.\n\nPleyer, L\n\nBurgstaller, S\n\nStauder, R\n\nGirschikofsky, M\n\nSill, H\n\nSchlick, K\n\nThaler, J\n\nHalter, B\n\nMachherndl-Spandl, S\n\nZebisch, A\n\nPichler, A\n\nPfeilstöcker, M\n\nAutzinger, EM\n\nLang, A\n\nGeissler, K\n\nVoskova, D\n\nGeissler, D\n\nSperr, WR\n\nHojas, S\n\nRogulj, IM\n\nAndel, J\n\nGreil, R\n\nBeiträge in Fachzeitschriften\nISI:000374143400001\n27084507.0\n10.1186/s13045-016-0263-4\nPMC4833933\nThe MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20-30 % bone marrow blasts (AML20-30, formerly MDS-RAEB-t) to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20-30 and AML30+ was made by regulatory agencies by initially restricting approval of azacitidine to AML20-30. Thus, uncertainty prevails regarding the diagnosis, prognosis and optimal treatment timing and strategy for patients with AML20-30. Here, we aim to provide clarification for patients treated with azacitidine front-line.\n The Austrian Azacitidine Registry is a multicentre database (ClinicalTrials.gov: NCT01595295). For this analysis, we selected 339 patients treated with azacitidine front-line. According to the WHO classification 53, 96 and 190 patients had MDS-RAEB-I, MDS-RAEB-II and AML (AML20-30: n = 79; AML30+: n = 111), respectively. According to the FAB classification, 131, 101 and 111 patients had MDS-RAEB, MDS-RAEB-t and AML, respectively.\n The median ages of patients with MDS and AML were 72 (range 37-87) and 77 (range 23-93) years, respectively. Overall, 80 % of classifiable patients (≤30 % bone marrow blasts) had intermediate-2 or high-risk IPSS scores. Most other baseline, treatment and response characteristics were similar between patients diagnosed with MDS or AML. WHO-classified patients with AML20-30 had significantly worse OS than patients with MDS-RAEB-II (13.1 vs 18.9 months; p = 0.010), but similar OS to patients with AML30+ (10.9 vs 13.1 months; p = 0.238). AML patients that showed MDS-related features did not have worse outcomes compared with patients who did not (13.2 vs 8.9 months; p = 0.104). FAB-classified patients with MDS-RAEB-t had similar survival to patients with AML30+ (12.8 vs 10.9 months; p = 0.376), but significantly worse OS than patients with MDS-RAEB (10.9 vs 24.4 months; p < 0.001).\n Our data demonstrate the validity of the WHO classification of MDS and AML, and its superiority over the former FAB classification, for patients treated with azacitidine front-line. Neither bone marrow blast count nor presence of MDS-related features had an adverse prognostic impact on survival. Patients with AML20-30 should therefore be regarded as having 'true AML' and in our opinion treatment should be initiated without delay.\n\nSill, Heinz\n\nZebisch, Armin\n\n\n"
},
{
"text": "\n168233\nLysyl oxidase-like protein 2 (LOXL2) modulates barrier function in cholangiocytes in cholestasis.\n\nPollheimer, MJ\n\nRacedo, S\n\nMikels-Vigdal, A\n\nMarshall, D\n\nBowlus, C\n\nLackner, C\n\nMadl, T\n\nKarlsen, TH\n\nHov, JR\n\nLyman, SK\n\nAdamkewicz, J\n\nSmith, V\n\nMoreau, E\n\nZollner, G\n\nEide, TJ\n\nStojakovic, T\n\nScharnagl, H\n\nGruber, HJ\n\nStauber, RE\n\nTrauner, M\n\nFickert, P\n\nBeiträge in Fachzeitschriften\nISI:000438753600016\n29709678.0\n10.1016/j.jhep.2018.04.009\nNone\nThe lysyl oxidase-like protein 2 (LOXL2) promotes stabilization of the extracellular matrix, chemotaxis, cell growth and cell mobility. We aimed to (i) identify stimuli of LOXL2 in cholangiopathies, (ii) characterize the effects of LOXL2 on biliary epithelial cells' (BECs) barrier function, (iii) compare LOXL2 expression in primary sclerosing cholangitis (PSC), primary biliary cholangitis, and disease controls, and (iv) to determine LOXL2 expression and its cellular sources in four mouse models of cholangiopathies.\n Cultured murine BECs were challenged with well-known triggers of cellular senescence, hypoxia, phospholipid-deficient Abcb4-/- mouse bile and chenodeoxycholic acid and investigated for LOXL2, SNAIL1 and E-cadherin expression and transepithelial electrical resistance with and without LOX-inhibition. In vivo, LOXL2 expression was studied in PSC livers, and controls and mouse models. We compared LOXL2 serum levels in patients with PSC, secondary SC, primary biliary cholangitis, and controls.\n Cellular senescence, hypoxia, Abcb4-/- bile and chenodeoxycholic acid induced LOXL2 and SNAIL1 expression, repressed E-cadherin expression, and significantly reduced transepithelial electrical resistance in BECs. Notably, all of the pathological changes could be recovered via pharmacological LOX-inhibition. Mouse models showed induced LOXL2 expression in the portal region and in association with ductular reaction. LOXL2 serum levels were significantly elevated in patients with cholangiopathies. In PSC, LOXL2 expression was located to characteristic periductal onion skin-type fibrosis, ductular reaction, Kupffer cells, and fibrotic septa. Importantly, in PSC, LOXL2 overexpression was paralleled by E-cadherin loss in BECs from medium-sized bile ducts.\n Reactive BECs produce LOXL2, resulting in increased tight junction permeability, which can be ameliorated by pharmacological LOX-inhibition in vitro. Reactive BECs, portal myofibroblasts, and Kupffer cells are the main sources of LOXL2 in cholangiopathies.\n In this study, we investigate the role of lysyl oxidase-like protein 2 (LOXL2), an enzyme pivotal in the development of organ fibrosis, in the pathogenesis of cholangiopathies (diseases of bile ducts), such as primary sclerosing cholangitis. We found LOXL2 to be expressed in association with bile duct epithelial injury and uncovered mechanisms for its upregulation and the subsequent effects in vitro and in vivo. Our findings support testing of anti-LOXL2 treatment strategies for patients with primary sclerosing cholangitis.\n Copyright © 2018 European Association for the Study of the Liver. All rights reserved.\n\nFickert, Peter\n\nGruber, Hans-Jürgen\n\nLackner, Karoline\n\nMadl, Tobias\n\nPollheimer, Marion\n\nRacedo, Silvia Maria\n\nScharnagl, Hubert\n\nStauber, Rudolf\n\nZollner, Gernot\n\n\n"
},
{
"text": "\n183987\nChronic kidney disease in the context of multimorbidity patterns: the role of physical performance : The screening for CKD among older people across Europe (SCOPE) study.\n\nCorsonello, A\n\nFabbietti, P\n\nFormiga, F\n\nMoreno-Gonzalez, R\n\nTap, L\n\nMattace-Raso, F\n\nRoller-Wirnsberger, R\n\nWirnsberger, G\n\nÄrnlöv, J\n\nCarlsson, AC\n\nWeingart, C\n\nFreiberger, E\n\nKostka, T\n\nGuligowska, A\n\nGil, P\n\nMartinez, SL\n\nMelzer, I\n\nYehoshua, I\n\nLattanzio, F\n\nSCOPE investigators\n\nBeiträge in Fachzeitschriften\nISI:000576901000007\n33008303.0\n10.1186/s12877-020-01696-4\nPMC7532089\nChronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients.\n Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson's disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR < 60, < 45 or < 30 ml/min/1.73 m2), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis.\n CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5-8 group, and hearing impairment in SPPB = 0-4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0-4 group. When defining CKD as eGFR< 45 or 30 ml/min/1.73 m2, the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR< 30 ml/min/1.73 m2) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer.\n CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters.\n The SCOPE study is registered at clinicaltrials.gov ( NCT02691546 ).\n\nRoller-Wirnsberger, Regina\n\nWirnsberger, Gerhard\n\n\n"
},
{
"text": "\n123173\nMRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study.\n\nLansberg, MG\n\nStraka, M\n\nKemp, S\n\nMlynash, M\n\nWechsler, LR\n\nJovin, TG\n\nWilder, MJ\n\nLutsep, HL\n\nCzartoski, TJ\n\nBernstein, RA\n\nChang, CWJ\n\nWarach, S\n\nFazekas, F\n\nInoue, M\n\nTipirneni, A\n\nHamilton, SA\n\nZaharchuk, G\n\nMarks, MP\n\nBammer, R\n\nAlbers, GW\n\n\n\nBeiträge in Fachzeitschriften\nISI:000309634300011\n22954705.0\n10.1016/S1474-4422(12)70203-X\nPMC4074206\nBackground Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. Methods In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data. Findings 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8.8 (95% CI 2.7-29.0) in the target mismatch group and 0.2 (0.0-1.6) in the no target mismatch group (p=0.003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4.0, 5% CI 1.3-12.2) in the target mismatch group, but not in the no target mismatch group (1.9, .2-18.7). Interpretation Target mismatch patients who had early reperfiision after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.\n\nFazekas, Franz\n\nSeifert-Held, Thomas\n\n\n"
},
{
"text": "\n146856\nLong-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment.\n\nKispal, ZF\n\nKardos, D\n\nJilling, T\n\nKereskai, L\n\nIsaacs, M\n\nBalogh, DL\n\nPinter, AB\n\nTill, H\n\nVajda, P\n\nBeiträge in Fachzeitschriften\nISI:000366715000013\n26298391.0\n10.1016/j.jpurol.2015.04.037\nNone\nBladder augmentation is widely used to treat otherwise unmanageable urinary incontinence. However, it is associated with a large number of complications, of which tumor formation is the most severe. Mucin proteins and MUC genes are linked, among others, to malignancies of the urinary bladder and the gastrointestinal system.\n To investigate histological alterations as well as changes in expression of MUC1 and MUC2 genes and proteins following different types of urinary bladder augmentation or substitution performed in children and adolescents.\n Between 1988 and 2013, 91 patients underwent urinary bladder augmentation or substitution at the study institute. Patients were included on whom cystoplasty had been performed 4 years previously or earlier, and could have been followed-up prospectively. Thus, 54 patients were involved in the study. In eight patients gastrocystoplasty was performed, in 17 patients ileocystoplasty, and in 22 patients colocystoplasty. Seven patients underwent bladder substitution using a colonic-segment. Biopsies were taken via cystoscopy from the native bladder, from the gastrointestinal segment used for augmentation, and from the anastomotic line between these two. One part of the samples was fixed in formaldehyde for routine histological processing. The other part of the biopsies was embedded into OCT medium, then cryosectioned and fluorescently double-immunostained for MUC1 and MUC2 proteins. Samples from the microscopically dysplastic lesions and from the 15-year-old or older biopsies were processed by laser capture microdissection, and then real-time PCR was done. Data were statistically analyzed by ANOVA and ordinary least squares regression tests.\n One adenocarcinoma was found in a female patient, 11 years after colocystoplasty. There were no significant changes in the level of MUC1 and MUC2 proteins and gene expression in the urothelium and in the gastrointestinal segment used for augmentation following ileocystoplasty and gastrocystoplasty. Significant increase in MUC1 and decrease in MUC2 protein levels were detected following colocystoplasty in the large bowel segment used for augmentation, both with qualitative and quantitative methods (p < 0.05) (Figure). The uroepithelium showed no significant change. RT-PCR revealed progressive increase in MUC1 gene expression and decrease in MUC2 gene expression after colocystoplasty in the course of time. It also showed highly increased MUC1 gene expression and decreased MUC2 gene expression in the samples of patients.\n Alterations in gene expression of MUC1 and MUC2 might serve as promising markers for early detection of histological changes after colocystoplasty.\n Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.\n\nTill, Holger\n\n\n"
},
{
"text": "\n182130\nSepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.\n\nIbarz, M\n\nBoumendil, A\n\nHaas, LEM\n\nIrazabal, M\n\nFlaatten, H\n\nde Lange, DW\n\nMorandi, A\n\nAndersen, FH\n\nBertolini, G\n\nCecconi, M\n\nChristensen, S\n\nFaraldi, L\n\nFjølner, J\n\nJung, C\n\nMarsh, B\n\nMoreno, R\n\nOeyen, S\n\nÖhman, CA\n\nBollen Pinto, B\n\nSoliman, IW\n\nSzczeklik, W\n\nValentin, A\n\nWatson, X\n\nZaferidis, T\n\nGuidet, B\n\nArtigas, A\n\nVIP1 study\n\nBeiträge in Fachzeitschriften\nISI:000536278100001\n32406016.0\n10.1186/s13613-020-00672-w\nPMC7221097\nThe number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.\n This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85].\n After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.\n\nEller, Philipp\n\n\n"
},
{
"text": "\n185072\nClinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.\n\nHofman, P\n\nIlié, M\n\nChamorey, E\n\nBrest, P\n\nSchiappa, R\n\nNakache, V\n\nAntoine, M\n\nBarberis, M\n\nBegueret, H\n\nBibeau, F\n\nBonnetaud, C\n\nBoström, P\n\nBrousset, P\n\nBubendorf, L\n\nCarvalho, L\n\nCathomas, G\n\nCazes, A\n\nChalabreysse, L\n\nChenard, MP\n\nCopin, MC\n\nCôté, JF\n\nDamotte, D\n\nde Leval, L\n\nDelongova, P\n\nThomas de Montpreville, V\n\nde Muret, A\n\nDema, A\n\nDietmaier, W\n\nEvert, M\n\nFabre, A\n\nForest, F\n\nFoulet, A\n\nGarcia, S\n\nGarcia-Martos, M\n\nGibault, L\n\nGorkiewicz, G\n\nJonigk, D\n\nGosney, J\n\nHofman, A\n\nKern, I\n\nKerr, K\n\nKossai, M\n\nKriegsmann, M\n\nLassalle, S\n\nLong-Mira, E\n\nLupo, A\n\nMamilos, A\n\nMatěj, R\n\nMeilleroux, J\n\nOrtiz-Villalón, C\n\nPanico, L\n\nPanizo, A\n\nPapotti, M\n\nPauwels, P\n\nPelosi, G\n\nPenault-Llorca, F\n\nPop, O\n\nPoté, N\n\nCajal, SRY\n\nSabourin, JC\n\nSalmon, I\n\nSajin, M\n\nSavic-Prince, S\n\nSchildhaus, HU\n\nSchirmacher, P\n\nSerre, I\n\nShaw, E\n\nSizaret, D\n\nStenzinger, A\n\nStojsic, J\n\nThunnissen, E\n\nTimens, W\n\nTroncone, G\n\nWerlein, C\n\nWolff, H\n\nBerthet, JP\n\nBenzaquen, J\n\nMarquette, CH\n\nHofman, V\n\nCalabrese, F\n\nBeiträge in Fachzeitschriften\nISI:000631402900022\n33399086.0\n10.1016/j.esmoop.2020.100024\nPMC7780004\nThis study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases.\n A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019.\n Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples.\n The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.\n Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nGorkiewicz, Gregor\n\n\n"
},
{
"text": "\n127924\nTumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.\n\nHeitzer, E\n\nUlz, P\n\nBelic, J\n\nGutschi, S\n\nQuehenberger, F\n\nFischereder, K\n\nBenezeder, T\n\nAuer, M\n\nPischler, C\n\nMannweiler, S\n\nPichler, M\n\nEisner, F\n\nHaeusler, M\n\nRiethdorf, S\n\nPantel, K\n\nSamonigg, H\n\nHoefler, G\n\nAugustin, H\n\nGeigl, JB\n\nSpeicher, MR\n\nBeiträge in Fachzeitschriften\nISI:000320102600001\n23561577.0\n10.1186/gm434\nPMC3707016\nPatients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.\n We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC).\n The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone.\n The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.\n\nAuer, Martina\n\nAugustin, Herbert\n\nBenezeder, Theresa Helena\n\nEisner, Florian\n\nGeigl, Jochen Bernd\n\nHeitzer, Ellen\n\nHöfler, Gerald\n\nMannweiler, Sebastian\n\nPichler, Martin\n\nPischler, Carina\n\nQuehenberger, Franz\n\nSamonigg, Hellmut\n\nSpeicher, Michael\n\nUlz, Peter\n\n\n"
},
{
"text": "\n143521\nConversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.\n\nKuhle, J\n\nDisanto, G\n\nDobson, R\n\nAdiutori, R\n\nBianchi, L\n\nTopping, J\n\nBestwick, JP\n\nMeier, UC\n\nMarta, M\n\nDalla Costa, G\n\nRunia, T\n\nEvdoshenko, E\n\nLazareva, N\n\nThouvenot, E\n\nIaffaldano, P\n\nDirenzo, V\n\nKhademi, M\n\nPiehl, F\n\nComabella, M\n\nSombekke, M\n\nKillestein, J\n\nHegen, H\n\nRauch, S\n\nD'Alfonso, S\n\nAlvarez-Cermeño, JC\n\nKleinová, P\n\nHoráková, D\n\nRoesler, R\n\nLauda, F\n\nLlufriu, S\n\nAvsar, T\n\nUygunoglu, U\n\nAltintas, A\n\nSaip, S\n\nMenge, T\n\nRajda, C\n\nBergamaschi, R\n\nMoll, N\n\nKhalil, M\n\nMarignier, R\n\nDujmovic, I\n\nLarsson, H\n\nMalmestrom, C\n\nScarpini, E\n\nFenoglio, C\n\nWergeland, S\n\nLaroni, A\n\nAnnibali, V\n\nRomano, S\n\nMartínez, AD\n\nCarra, A\n\nSalvetti, M\n\nUccelli, A\n\nTorkildsen, Ø\n\nMyhr, KM\n\nGalimberti, D\n\nRejdak, K\n\nLycke, J\n\nFrederiksen, JL\n\nDrulovic, J\n\nConfavreux, C\n\nBrassat, D\n\nEnzinger, C\n\nFuchs, S\n\nBosca, I\n\nPelletier, J\n\nPicard, C\n\nColombo, E\n\nFranciotta, D\n\nDerfuss, T\n\nLindberg, R\n\nYaldizli, Ö\n\nVécsei, L\n\nKieseier, BC\n\nHartung, HP\n\nVilloslada, P\n\nSiva, A\n\nSaiz, A\n\nTumani, H\n\nHavrdová, E\n\nVillar, LM\n\nLeone, M\n\nBarizzone, N\n\nDeisenhammer, F\n\nTeunissen, C\n\nMontalban, X\n\nTintoré, M\n\nOlsson, T\n\nTrojano, M\n\nLehmann, S\n\nCastelnovo, G\n\nLapin, S\n\nHintzen, R\n\nKappos, L\n\nFurlan, R\n\nMartinelli, V\n\nComi, G\n\nRamagopalan, SV\n\nGiovannoni, G\n\nBeiträge in Fachzeitschriften\nISI:000357738700009\n25680984.0\n10.1177/1352458514568827\nNone\nWe explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort.\n Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS.\n At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres.\n We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.\n © The Author(s), 2015.\n\nEnzinger, Christian\n\nFuchs, Siegrid\n\nKhalil, Michael\n\n\n"
}
]
}