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"text": "\n155819\nThe role and value of sirolimus administration in kidney and liver transplantation.\n\nMehrabi, A\n\nFonouni, H\n\nKashfi, A\n\nSchmied, BM\n\nMorath, Ch\n\nSadeghi, M\n\nSchemmer, P\n\nEncke, J\n\nSauer, P\n\nZeier, M\n\nWeitz, J\n\nBüchler, MW\n\nSchmidt, J\n\nBeiträge in Fachzeitschriften\nISI:000242602600006\n17100699.0\n10.1111/j.1399-0012.2006.00598.x\nNone\nEnormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n173812\nVitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction.\n\nNolte, K\n\nHerrmann-Lingen, C\n\nPlatschek, L\n\nHolzendorf, V\n\nPilz, S\n\nTomaschitz, A\n\nDüngen, HD\n\nAngermann, CE\n\nHasenfuß, G\n\nPieske, B\n\nWachter, R\n\nEdelmann, F\n\nBeiträge in Fachzeitschriften\nISI:000464451900004\n30784226.0\n10.1002/ehf2.12413\nPMC6437442\nVitamin D deficiency is prevalent in heart failure (HF), but its relevance in early stages of heart failure with preserved ejection fraction (HFpEF) is unknown. We tested the association of 25-hydroxyvitamin D [25(OH)D] serum levels with mortality, hospitalizations, cardiovascular risk factors, and echocardiographic parameters in patients with asymptomatic diastolic dysfunction (DD) or newly diagnosed HFpEF.\n We measured 25(OH)D serum levels in outpatients with risk factors for DD or history of HF derived from the DIAST-CHF study. Participants were comprehensively phenotyped including physical examination, echocardiography, and 6 min walk test and were followed up to 5 years. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. We included 787 patients with available 25(OH)D levels. Median 25(OH)D levels were 13.1 ng/mL, mean E/e' medial was 13.2, and mean left ventricular ejection fraction was 59.1%. Only 9% (n = 73) showed a left ventricular ejection fraction <50%. Fifteen per cent (n = 119) of the recruited participants had symptomatic HFpEF. At baseline, participants with 25(OH)D levels in the lowest tertile (≤10.9 ng/L; n = 263) were older, more often symptomatic (oedema and fatigue, all P ≤ 0.002) and had worse cardiac [higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and left atrial volume index, both P ≤ 0.023], renal (lower glomerular filtration rate, P = 0.012), metabolic (higher uric acid levels, P < 0.001), and functional (reduced exercise capacity, 6 min walk distance, and SF-36 physical functioning score, all P < 0.001) parameters. Increased NT-proBNP, uric acid, and left atrial volume index and decreased SF-36 physical functioning scores were independently associated with lower 25(OH)D levels. There was a higher risk for lower 25(OH)D levels in association with HF, DD, and atrial fibrillation (all P ≤ 0.004), which remained significant after adjusting for age. Lower 25(OH)D levels (per 10 ng/mL decrease) tended to be associated with higher 5 year mortality, P = 0.05, hazard ratio (HR) 1.55 [1.00; 2.42]. Furthermore, lower 25(OH)D levels (per 10 ng/mL decrease) were related to an increased rate of cardiovascular hospitalizations, P = 0.023, HR = 1.74 [1.08; 2.80], and remained significant after adjusting for age, P = 0.046, HR = 1.63 [1.01; 2.64], baseline NT-proBNP, P = 0.048, HR = 1.62 [1.01; 2.61], and other selected baseline characteristics and co-morbidities, P = 0.043, HR = 3.60 [1.04; 12.43].\n Lower 25(OH)D levels were associated with reduced functional capacity in patients with DD or HFpEF and were significantly predictive for an increased rate of cardiovascular hospitalizations, also after adjusting for age, NT-proBNP, and selected baseline characteristics and co-morbidities.\n © 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.\n\nPilz, Stefan\n\n\n"
},
{
"text": "\n2983\nReagent or myeloperoxidase-generated hypochlorite affects discrete regions in lipid-free and lipid-associated human apolipoprotein A-I.\n\nBergt, C\n\nOettl, K\n\nKeller, W\n\nAndreae, F\n\nLeis, HJ\n\nMalle, E\n\nSattler, W\n\nBeiträge in Fachzeitschriften\nISI:000085977300013\n10677352.0\n10.1042%2F0264-6021%3A3460345\nPMC1220859\nWe have previously shown that the modification of high-density lipoprotein subclass 3 (HDL(3)) by HOCl transformed an anti-atherogenic lipoprotein into a high-uptake form for macrophages and caused a significant impairment of cholesterol efflux capacity [Panzenboeck, Raitmayer, Reicher, Lindner, Glatter, Malle and Sattler (1997) J. Biol. Chem. 272, 29711-29720]. To elucidate the consequences of treatment with OCl(-) on distinct regions in apolipoprotein A-I (apo A-I), lipid-free and lipid-associated apo A-I were modified with increasing molar ratios of NaOCl or HOCl generated by the myeloperoxidase/H(2)O(2)/Cl(-) system. CD analysis revealed a pronounced decrease in alpha-helicity for lipid-free apo A-I modified by NaOCl, whereas lipid-associated apo A-I was less affected. The modification of apo A-I by NaOCl (molar oxidant-to-lipoprotein ratio 6:1) resulted in the formation of two distinct oxidized forms of apo A-I with molecular masses 32 or 48 atomic mass units (a.m.u.) higher than that of native apo A-I, indicating the addition of two or three oxygen atoms to the native protein. HPLC analysis of tryptic digests obtained from lipid-free and lipid-associated apo A-I modified with increasing oxidant-to-apolipoprotein molar ratios revealed a concentration-dependent modification of apo A-I: at a low molar oxidant-to-lipoprotein ratio (5:1) the peaks corresponding to the methionine-containing tryptic peptides T11 (residues 84-88), T16 (residues 108-116) and T22 (residues 141-149), located in the central region of apo A-I, disappeared. Their loss was accompanied by the formation of three oxidation products with a molecular mass 16 a.m.u. higher than that of the native peptides. This indicates the addition of oxygen, most probably caused by the oxidation of Met(86), Met(112) and Met(148) to the corresponding methionine sulphoxides. At a molar NaOCl-to-apo A-I ratio of 10:1 the disappearance of peptides T1 (residues 1-10), T7 (residues 46-59) and T9 (residues 62-77) was accompanied by the occurrence of new peaks 33.5 and 33.1 a.m.u. higher than those of the native peptides. Amino acid analyses of peptides T7 and T9 after modification with NaOCl confirmed that Phe(57) and Phe(71) were primary targets for oxidation by HOCl. GLC-MS analysis of hydrolysates obtained from OCl(-)-modified T7, T9, apo A-I and HDL(3) confirmed that Phe residues are an early target for OCl(-) modification. At molar NaOCl-to-apo A-I ratios of 25:1, the peak areas of peptides T31 (residues 189-195) and T32 (residues 196-206) decreased markedly. Most importantly, incubation of apo A-I with the myeloperoxidase/H(2)O(2)/Cl(-) system (the source of HOCl in vivo) resulted in almost identical modification patterns to those observed with reagent NaOCl.\n\nLeis, Hans-Joerg\n\nMalle, Ernst\n\nÖttl, Karl\n\nSattler, Wolfgang\n\n\n"
},
{
"text": "\n118538\nGenome-wide association and functional follow-up reveals new loci for kidney function.\n\nPattaro, C\n\nKöttgen, A\n\nTeumer, A\n\nGarnaas, M\n\nBöger, CA\n\nFuchsberger, C\n\nOlden, M\n\nChen, MH\n\nTin, A\n\nTaliun, D\n\nLi, M\n\nGao, X\n\nGorski, M\n\nYang, Q\n\nHundertmark, C\n\nFoster, MC\n\nO'Seaghdha, CM\n\nGlazer, N\n\nIsaacs, A\n\nLiu, CT\n\nSmith, AV\n\nO'Connell, JR\n\nStruchalin, M\n\nTanaka, T\n\nLi, G\n\nJohnson, AD\n\nGierman, HJ\n\nFeitosa, M\n\nHwang, SJ\n\nAtkinson, EJ\n\nLohman, K\n\nCornelis, MC\n\nJohansson, Å\n\nTönjes, A\n\nDehghan, A\n\nChouraki, V\n\nHolliday, EG\n\nSorice, R\n\nKutalik, Z\n\nLehtimäki, T\n\nEsko, T\n\nDeshmukh, H\n\nUlivi, S\n\nChu, AY\n\nMurgia, F\n\nTrompet, S\n\nImboden, M\n\nKollerits, B\n\nPistis, G\n\nCARDIoGRAM Consortium\n\nICBP Consortium\n\nCARe Consortium\n\nWellcome Trust Case Control Consortium 2 (WTCCC2)\n\nHarris, TB\n\nLauner, LJ\n\nAspelund, T\n\nEiriksdottir, G\n\nMitchell, BD\n\nBoerwinkle, E\n\nSchmidt, H\n\nCavalieri, M\n\nRao, M\n\nHu, FB\n\nDemirkan, A\n\nOostra, BA\n\nde Andrade, M\n\nTurner, ST\n\nDing, J\n\nAndrews, JS\n\nFreedman, BI\n\nKoenig, W\n\nIllig, T\n\nDöring, A\n\nWichmann, HE\n\nKolcic, I\n\nZemunik, T\n\nBoban, M\n\nMinelli, C\n\nWheeler, HE\n\nIgl, W\n\nZaboli, G\n\nWild, SH\n\nWright, AF\n\nCampbell, H\n\nEllinghaus, D\n\nNöthlings, U\n\nJacobs, G\n\nBiffar, R\n\nEndlich, K\n\nErnst, F\n\nHomuth, G\n\nKroemer, HK\n\nNauck, M\n\nStracke, S\n\nVölker, U\n\nVölzke, H\n\nKovacs, P\n\nStumvoll, M\n\nMägi, R\n\nHofman, A\n\nUitterlinden, AG\n\nRivadeneira, F\n\nAulchenko, YS\n\nPolasek, O\n\nHastie, N\n\nVitart, V\n\nHelmer, C\n\nWang, JJ\n\nRuggiero, D\n\nBergmann, S\n\nKähönen, M\n\nViikari, J\n\nNikopensius, T\n\nProvince, M\n\nKetkar, S\n\nColhoun, H\n\nDoney, A\n\nRobino, A\n\nGiulianini, F\n\nKrämer, BK\n\nPortas, L\n\nFord, I\n\nBuckley, BM\n\nAdam, M\n\nThun, GA\n\nPaulweber, B\n\nHaun, M\n\nSala, C\n\nMetzger, M\n\nMitchell, P\n\nCiullo, M\n\nKim, SK\n\nVollenweider, P\n\nRaitakari, O\n\nMetspalu, A\n\nPalmer, C\n\nGasparini, P\n\nPirastu, M\n\nJukema, JW\n\nProbst-Hensch, NM\n\nKronenberg, F\n\nToniolo, D\n\nGudnason, V\n\nShuldiner, AR\n\nCoresh, J\n\nSchmidt, R\n\nFerrucci, L\n\nSiscovick, DS\n\nvan Duijn, CM\n\nBorecki, I\n\nKardia, SL\n\nLiu, Y\n\nCurhan, GC\n\nRudan, I\n\nGyllensten, U\n\nWilson, JF\n\nFranke, A\n\nPramstaller, PP\n\nRettig, R\n\nProkopenko, I\n\nWitteman, JC\n\nHayward, C\n\nRidker, P\n\nParsa, A\n\nBochud, M\n\nHeid, IM\n\nGoessling, W\n\nChasman, DI\n\nKao, WH\n\nFox, CS\n\nBeiträge in Fachzeitschriften\nISI:000302254800059\n22479191.0\n10.1371/journal.pgen.1002584\nPMC3315455\nChronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130, 00 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.\n\nCavalieri, Margherita\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n146550\nIs Embolization an Effective Treatment for Recurrent Hemorrhage After Hip or Knee Arthroplasty?\n\nKalmar, PI\n\nLeithner, A\n\nEhall, R\n\nPortugaller, RH\n\nBeiträge in Fachzeitschriften\nISI:000368022600048\n26220895.0\n10.1007/s11999-015-4476-6\nPMC4686488\nSpontaneous recurrent hemorrhage after arthroplasty of the hip or knee is a rare condition. In patients who do not have coagulopathy, the likeliest etiology for hemarthrosis is hypertrophic vascular synovium. Treatments include arthroscopic or open synovectomy, or angiography with embolization; however, because the condition is rare, seldom reported, and debilitating, small case series characterizing the efficacy of any approach are important to allow a collective experience with this condition to emerge.\n We attempted to (1) determine whether angiography with embolization can prevent recurrent hemarthrosis after hip or knee arthroplasty in a small series of patients with or without coagulopathy, and (2) evaluate complications associated with this intervention.\n Between 2005 and 2014, seven patients presented with spontaneous, recurrent hemarthroses. One patient had polycythemia vera and factor XIII deficiency as underlying illnesses. All patients were treated with selective transarterial embolization, and all had followup at a minimum of 12 months (range, 12-102 months; median, 74 months). Other treatments during this time included hematoma removals and flap operations in one patient, and indications for transarterial embolization included recurrent hemarthrosis. The patients included six men and one woman with a median age of 72 years (range, 61-78 years). Five patients underwent one or more reoperations before transarterial embolization. A diagnostic workup for coagulopathy was performed in all patients; one patient was identified to have polycythemia ruba vera and factor XIII deficiency, however the patient still was treated with transarterial embolization because it was perceived to be the least invasive of available options. No other patients had a diagnosis of coagulopathy. Angiography showed hypervascularity in all patients and a contrast agent showed extravasation in two. Selective transarterial embolization of branches of the internal iliac artery, common femoral artery, deep femoral artery, or the popliteal artery was performed with polyvinyl alcohol particles, microspheres, and/or coils. Patients were followed clinically during 12 to 102 months (median, 74 months) to determine whether the hemorrhages recurred.\n Technical success was achieved in all patients. No procedure-related complications were reported. On followup, recurrent hemorrhage was reported in one patient who had a diagnosis of coagulopathy before the procedure. He underwent three reinterventions and five reoperations. Three months after initial embolization, a flap procedure was performed.\n In a small series of patients with a minimum followup of 1 year, we found selective transarterial embolization to be effective in patients without underlying coagulopathy in preventing recurrences of spontaneous recurrent hematoma or hemarthrosis of the hip and the knee. This condition is rare, therefore comparative trials are unlikely to be done. Because transarterial embolization is relatively low risk and generally well tolerated, we consider it to be a reasonable approach for consideration with other options such as arthroscopic or open synovectomy and revision arthroplasty.\n Level IV, therapeutic study.\n\nKalmar, Peter\n\nLeithner, Andreas\n\nPortugaller, Rupert\n\n\n"
},
{
"text": "\n152328\nSutureless, rapid deployment valves and stented bioprosthesis in aortic valve replacement: recommendations of an International Expert Consensus Panel.\n\nGersak, B\n\nFischlein, T\n\nFolliguet, TA\n\nMeuris, B\n\nTeoh, KH\n\nMoten, SC\n\nSolinas, M\n\nMiceli, A\n\nOberwalder, PJ\n\nRambaldini, M\n\nBhatnagar, G\n\nBorger, MA\n\nBouchard, D\n\nBouchot, O\n\nClark, SC\n\nDapunt, OE\n\nFerrarini, M\n\nLaufer, G\n\nMignosa, C\n\nMillner, R\n\nNoirhomme, P\n\nPfeiffer, S\n\nRuyra-Baliarda, X\n\nShrestha, M\n\nSuri, RM\n\nTroise, G\n\nDiegeler, A\n\nLaborde, F\n\nLaskar, M\n\nNajm, HK\n\nGlauber, M\n\nBeiträge in Fachzeitschriften\nISI:000372977500003\n26516193.0\n10.1093/ejcts/ezv369\nNone\nAfter a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves.\n Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts.\n Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19-27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves.\n The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.\n © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.\n\nOberwalder, Peter\n\n\n"
},
{
"text": "\n90644\nAssessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography.\n\nErgun, E\n\nHermann, B\n\nWirtitsch, M\n\nUnterhuber, A\n\nKo, TH\n\nSattmann, H\n\nScholda, C\n\nFujimoto, JG\n\nStur, M\n\nDrexler, W\n\nBeiträge in Fachzeitschriften\nISI:000226469100046\n15623790.0\n10.1167/iovs.04-0212\nNone\nPURPOSE: To assess photoreceptor morphology in patients with Stargardt's disease and fundus flavimaculatus using ultrahigh-resolution optical coherence tomography (UHR-OCT) and correlate it with visual acuity (VA). METHODS: This was a prospective observational case series. Fourteen patients with Stargardt's disease (nine women, five men; average age, 39 years; range, 27-53) were examined. A clinically viable UHR-OCT system employing a new, compact titanium sapphire laser was used, enabling a 3-microm axial resolution in the retina. All patients received a full ophthalmic examination, including fluorescein angiography. Outcome was judged by central transverse photoreceptor loss, central foveal thickness, VA, central atrophy according to fluorescein angiography, and fundus autofluorescence. RESULTS: UHR-OCT was capable of visualizing and quantifying regions of central transverse photoreceptor (PR) loss. All Stargardt patients with central atrophy had a complete loss of the central photoreceptor layer in the foveal region (mean transverse photoreceptor loss, 4390 +/- 2270 microm; range, 530-9240 microm). Patients without clinically evident central atrophy had an intact photoreceptor layer centrally, but had small, focal parafoveal defects. A correlation was detected between VA and transverse PR loss (Spearman rho=-0.60, P=0.03), which was confirmed on logistic regression analysis (R2=0.49, P=0.0001). Central foveal thickness was reduced in patients with Stargardt's disease (85 +/- 40 microm; range, 58-280 microm). The correlation was statistically significant with VA (Spearman rho=0.43, P=0.04), but not with transverse PR loss (Spearman rho=-0.23, P >>0.05). Linear regression analysis showed a statistically significant association of central foveal thickness with VA (R2=0.51, P=0.0001), but not with transverse PR loss (P >>0.05). The extent of atrophy seen in fluorescein angiography correlated with VA and transverse PR loss (Spearman rho=-0.51, P=0.007; Spearman rho=0.77, P=0.0001). Similar correlations were found with the maximum transverse diameter of fundus autofluorescence (Spearman rho=-0.72, P=0.008; Spearman rho=0.77, P=0.003). CONCLUSIONS: Ultrahigh-resolution OCT demonstrates excellent visualization of intraretinal morphology and enables quantification of the photoreceptor layer. Thus, for the first time, an in vivo visualization and quantification of transverse, central photoreceptor loss and correlation with visual function is possible. Lower VA corresponds to a greater transverse photoreceptor loss, which also correlates with the extent of changes seen in fluorescein angiography and in fundus autofluorescence. Furthermore, reduced retinal thickness (i.e., atrophy of retinal layers) does not correlate with the transverse extent of PR loss. Thus, it seems that although there may be progressive atrophy of intraretinal layers, an intact photoreceptor layer leads to better VA. UHR-OCT may present a viable alternative to the assessment of central visual function, due to the easy, objective, and noninvasive data acquisition. Therefore, UHR-OCT could be of future use in judging patients' prognoses in Stargardt's disease.\n\n\n"
},
{
"text": "\n2384\nSoluble CD44 v5 and v6 in serum of patients with breast cancer. Correlation with expression of CD44 v5 and v6 variants in primary tumors and location of distant metastasis.\n\nLackner, C\n\nMoser, R\n\nBauernhofer, T\n\nWilders-Truschnig, M\n\nSamonigg, H\n\nBerghold, A\n\nZatloukal, K\n\nBeiträge in Fachzeitschriften\nISI:000071963500004\n9493973.0\n10.1023%2FA%3A1005913514376\nNone\nPrimary breast cancers were shown to overexpress CD44 v5 and v6 at the plasma membrane. However, the clinical significance of this overexpression remains unclear. Overexpression of CD44 v5 and v6 in primary breast cancers was found to correlate with metastasis and poor prognosis by some investigators, yet this correlation could not be confirmed by others using different antibodies. In this study the influence of metastatic disease, the site of metastasis, and the amount of CD44 v5 and v6 expression in the primary tumor on serum levels of the soluble forms of CD44 v5 and v6 (sCD44 v5 and v6) in breast cancer patients was investigated. Soluble CD44 v5 and v6 serum levels were measured by enzyme linked immuno sorbent assay in a group of breast cancer patients who developed metastases in various organs and in another group of patients with single organ metastasis. For control, sCD44 v5 and v6 levels were measured in breast cancer patients who remained free of metastasis and in healthy blood donors. Expression of plasma membrane bound CD44 v5 and v6 in the primary tumors of the patients with metastasis in various organs was correlated to sCD44 v5 and v6 levels in serum. Furthermore the size of sCD44 v6 was analyzed by immunoblot using a monoclonal antibody directed against CD44 v6. When metastases were detected, sCD44 v5 and v6 serum levels were increased as compared to levels measured one month after tumor surgery in patients free of metastases (p= 0.0025 and p=0.0004). Six of 19 and 6 of 20 patients had sCD44 v5 and v6 serum levels above a cut-off level of 85 and 275 ng/mL, respectively. In these cases expression of CD44 v5 and v6 in the primary cancers was also elevated. Low sCD44 v5 and v6 serum levels were associated with weak expression of CD44 v5 and v6 in the respective primary cancers. As shown by statistical analysis of sCD44 v5 and v6 levels in 57 patients with single organ metastases, elevated sCD44 v6 levels but not sCD44 v5 levels were associated with metastases in liver or bone (p=0.0025). Immunoblot analysis of soluble CD44 proteins in serum revealed two CD44 v6 specific signals of approximately 120 and 170 kDa. Increased sCD44 v5 and v6 serum levels in patients with breast cancer were influenced by the amount of CD44 v5 and v6 expression in the primary tumor by the site of metastasis. Elevated sCD44 v6 serum levels were preferentially found in patients with metastases in liver or bone.\n\nBauernhofer, Thomas\n\nBerghold, Andrea\n\nLackner, Karoline\n\nSamonigg, Hellmut\n\nSchaberl-Moser, Renate\n\nZatloukal, Kurt\n\n\n"
},
{
"text": "\n184260\nMaternal Obesity Affects the Glucose-Insulin Axis During the First Trimester of Human Pregnancy.\n\nBandres-Meriz, J\n\nDieberger, AM\n\nHoch, D\n\nPochlauer, C\n\nBachbauer, M\n\nGlasner, A\n\nNiedrist, T\n\nvan Poppel, MNM\n\nDesoye, G\n\nBeiträge in Fachzeitschriften\nISI:000581087300001\n33154737.0\n10.3389/fendo.2020.566673\nPMC7586307\nBackground and objective: The maternal glucose-insulin axis is central for metabolic adaptations required for a healthy pregnancy. Metabolic changes in obese mothers in early pregnancy have been scantly described. Here we characterized the glucose-insulin axis in the first trimester of human pregnancy and assessed the effect of maternal obesity and fat mass. Methods: In this cross-sectional study, maternal blood samples (N = 323) were collected during voluntary pregnancy termination (gestational age 4+0-11+6 weeks) after overnight fasting. Smokers (N = 198) were identified by self-report and serum cotinine levels (ELISA). Maternal BMI (kg/m2) and serum leptin (ELISA) were used as proxy measures of obesity and maternal fat mass, respectively. BMI was categorized into under-/normal weight (BMI < 25.0 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI ≥ 30.0 kg/m2), and leptin in tertiles (1st tertile: leptin < 6.80 ng/ml, 2nd tertile: leptin 6.80-12.89 ng/ml, 3rd tertile: leptin > 12.89 ng/ml). ISHOMA insulin sensitivity index was calculated from glucose and C-peptide (ELISA) serum concentrations. Analyses of covariance including multiple confounders were performed to test for differences in glucose, C-peptide and ISHOMA between gestational age periods, BMI and leptin groups. C-peptide and ISHOMA were log-transformed before analyses. Results: At weeks 7-9, fasting glucose and C-peptide levels were lower (P < 0.01 and P < 0.001, respectively) and insulin sensitivity higher (P < 0.001) than at weeks 4-6. Glucose levels were not significantly different between BMI or leptin categories. In contrast, C-peptide increased by 19% (P < 0.01) between the normal weight and the overweight group and by 39% (P < 0.001) between the overweight and obese group. In the leptin groups, C-peptide increased by 25% (P < 0.001) between the 1st and 2nd leptin tertile and by 15% (P < 0.05) between the 2nd and 3rd leptin tertile. ISHOMA decreased with higher BMI and fat mass. ISHOMA decreased by 18% (P < 0.01) between the normal weight and the overweight group and by 30% (P < 0.01) between the overweight and the obese group. In the leptin groups, ISHOMA decreased by 22% (P < 0.001) between the 1st and 2nd leptin tertile and by 14% (P < 0.05) between the 2nd and 3rd leptin tertile. Conclusions: At the group level, fasting glucose, C-peptide and insulin sensitivity dynamically change in the first trimester of human pregnancy. Maternal obesity is associated with higher C-peptide and lower insulin sensitivity at all periods in the first trimester of human pregnancy, while glucose is unaltered. These findings have implications for the timing of early gestational diabetes mellitus risk screening.\n Copyright © 2020 Bandres-Meriz, Dieberger, Hoch, Pöchlauer, Bachbauer, Glasner, Niedrist, van Poppel and Desoye.\n\nBandrés Mériz, Julia\n\nDesoye, Gernot\n\nDieberger, Anna Maria\n\nHoch, Denise\n\nNiedrist, Tobias\n\n\n"
},
{
"text": "\n142588\nMobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: an analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.\n\nNagler, A\n\nLabopin, M\n\nShimoni, A\n\nNiederwieser, D\n\nMufti, GJ\n\nZander, AR\n\nArnold, R\n\nGreinix, H\n\nCornelissen, JJ\n\nJackson, GH\n\nCraddock, C\n\nBunjes, DW\n\nGanser, A\n\nRussell, NH\n\nKyrcz-Krzemien, S\n\nRocha, V\n\nMohty, M\n\nBeiträge in Fachzeitschriften\nISI:000308122200015\n22446014.0\n10.1016/j.bbmt.2012.02.013\nNone\nReduced-intensity conditioning allogeneic stem cell transplant (RIC-alloSCT) is being increasingly used for patients with acute myelogenous leukemia (AML) with comorbidities. Few published data are currently available regarding for the use of peripheral blood stem cells (PBSCs) compared to bone marrow (BM) in the RIC-alloSCT using unrelated donors (URDs). This retrospective report compared the outcomes of PBSC versus BM RIC-alloSCT. Between 2000 and 2007, 602 patients with AML in complete remission (CR) underwent RIC-alloSCT from URDs with PBSC (508) or BM (94) grafts. Recipient's age was higher in the PBSC versus BM groups 57 (range, 17-77 years) and 51 (range, 17-76 years), respectively (P < .0001). Leukemia features and disease status at RIC-alloSCT were also comparable between the PBSC versus BM groups. Engraftment was achieved in 97% and 96% with BM versus peripheral blood (PB), respectively. Acute graft-versus-host disease (aGVHD) grade >II was significantly higher in the PBSC group: 27% versus 12% in the BM group (P < .002). Similarly, chronic graft-versus-host disease (cGVHD; at 2 years) was somewhat higher in the PBSC group with 43% ± 3% versus 35% ± 6% in the BM group, respectively (P = .04). The 2-year probabilities of leukemia-free survival (LFS) were 46% ± 3% for the PBSC group in comparison to 43% ± 6% for the BM transplant group (P = NS), whereas relapse incidence was significantly higher in the BM versus the PB transplant group: 46% ± 6% versus 32% ± 3%, respectively (P = .014). Non-relapse mortality (NRM) was significantly higher for the PBSC versus the BM group: 28% ± 2% versus 13% ± 4%, respectively (P = .004). In multivariate analysis, after adjustment for differences between both groups, the PBSC group was associated with a higher incidence of aGVHD (grade II-IV; hazard ratio [HR] = 2.33; P = .06), higher NRM (HR = 2.3; P = .015), and a decreased relapse incidence (HR, 0.61; P = .02) with no statistical difference of LFS between the 2 groups (P = .88). In conclusion, our results indicate significantly higher incidence of aGVHD and NRM and a lower incidence of relapse but not statistically different LFS comparing unrelated PBSC to BM grafts after RIC-alloSCT.\n Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n4561\nUse of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.\n\nSpahn, DR\n\nWaschke, KF\n\nStandl, T\n\nMotsch, J\n\nVan Huynegem, L\n\nWelte, M\n\nGombotz, H\n\nCoriat, P\n\nVerkh, L\n\nFaithfull, S\n\nKeipert, P\n\nEuropean Perflubron Emulsion in Non-Cardiac Surgery Study Group\n\nBeiträge in Fachzeitschriften\nISI:000179590500003\n12459658.0\n10.1097%2F00000542-200212000-00004\nNone\nBACKGROUND: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. METHODS: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. RESULTS: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53% vs. 43%, < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit; P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss > or = 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26% vs. 16% in the PFC and control groups, respectively; P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units; P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%; P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4% vs. controls, 2%) was not statistically significant. CONCLUSIONS: Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.\n\n\n"
},
{
"text": "\n99288\nPathology of asbestosis- An update of the diagnostic criteria: Report of the asbestosis committee of the college of american pathologists and pulmonary pathology society.\n\nRoggli, VL\n\nGibbs, AR\n\nAttanoos, R\n\nChurg, A\n\nPopper, H\n\nCagle, P\n\nCorrin, B\n\nFranks, TJ\n\nGalateau-Salle, F\n\nGalvin, J\n\nHasleton, PS\n\nHenderson, DW\n\nHonma, K\n\nBeiträge in Fachzeitschriften\nISI:000275529200017\n20196674.0\nNone\nNone\nAsbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms. DIFFERENTIAL DIAGNOSIS: IDIOPATHIC PULMONARY FIBROSIS: The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis. DIFFERENTIAL DIAGNOSIS: RESPIRATORY BRONCHIOLITIS: Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis. ROLE OF ASBESTOS BODIES: Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5- mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests. ROLE OF FIBER ANALYSIS: Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.\n\nPopper, Helmuth\n\n\n"
},
{
"text": "\n120303\nFeatures associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project).\n\nBrookman-May, S\n\nMay, M\n\nShariat, SF\n\nXylinas, E\n\nStief, C\n\nZigeuner, R\n\nChromecki, T\n\nBurger, M\n\nWieland, WF\n\nCindolo, L\n\nSchips, L\n\nDe Cobelli, O\n\nRocco, B\n\nDe Nunzio, C\n\nFeciche, B\n\nTruss, M\n\nGilfrich, C\n\nPahernik, S\n\nHohenfellner, M\n\nZastrow, S\n\nWirth, MP\n\nNovara, G\n\nCarini, M\n\nMinervini, A\n\nSimeone, C\n\nAntonelli, A\n\nMirone, V\n\nLongo, N\n\nSimonato, A\n\nCarmignani, G\n\nFicarra, V\n\nMembers of the CORONA project and the SATURN project\n\nBeiträge in Fachzeitschriften\nISI:000323938700034\n22748912.0\n10.1016/j.eururo.2012.06.030\nNone\nBackground: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). Objective: To determine features associated with late recurrence. Design, setting, and participants: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). Interventions: Patients underwent radical nephrectomy or nephron-sparing surgery. Outcome measurements and statistical analysis: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). Results and limitations: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3-4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate-and poor-prognosis group(area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p < 0.001), pT stage (HR: 1.24; p < 0.001), Fuhrman grade (HR: 2.40; p < 0.001), age (HR: 1.01; p < 0.001), and gender (HR: 0.71; p = 0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. Conclusions: LVI, Fuhrman grade 3/4, and a tumor stage>pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n86047\nUse of keratin 34 beta E12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type - Benign and malignant intraductal proliferations\n\nMoinfar, F\n\nMan, YG\n\nLininger, RA\n\nBodian, C\n\nTavassoli, FA\n\nBeiträge in Fachzeitschriften\nISI:000082348800007\nNone\n10.1097/00000478-199909000-00007\nNone\nA variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34 beta E12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300, The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction thigh to very high scores) fur CK-34 beta E12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34 beta E12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH thigh to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34 beta E12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH thigh to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34 beta E12 is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We recommend the use of CK-34 beta E12 as an adjunct in the diagnosis of a variety of problematic intraductal proliferations of the breast.\n\nMoinfar, Farid\n\n\n"
},
{
"text": "\n149155\nRole of Ki-67 as a prognostic factor in gastrointestinal stromal tumors.\n\nBelev, B\n\nBrčić, I\n\nPrejac, J\n\nGolubić, ZA\n\nVrbanec, D\n\nBožikov, J\n\nAlerić, I\n\nBoban, M\n\nRazumović, JJ\n\nBeiträge in Fachzeitschriften\nISI:000314211200011\n23382631.0\n10.3748/wjg.v19.i4.523\nPMC3558576\nTo investigate primarily the prognostic value of Ki-67, as well as other parameters, in gastrointestinal stromal tumors (GISTs).\n Ki-67, c-KIT, platelet-derived growth factor receptor-alpha (PDGFRα), smooth muscle actin (SMA), CD34, S100 were stained for immunohistochemistry which was performed on formalin-fixed, paraffin-embeded sections on representative block from each case. Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells. Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively (weak, intermediate, strong) and for c-KIT type of reactivity was analyzed (cytoplasmic, membrane and "dot-like" staining). Immunoreactivity for SMA, CD34 and S100 were was evaluated as positive or negative antigen expression. Pathologic parameters investigated in this study included tumor size, cell type (pure spindle, pured epitheloid mixed spindle and epitheloid), mitotic count, hemorrhage, necrosis, mucosal ulceration. Clinical data included age, gender, primary tumor location and spread of disease. χ² test and Student's t-test were used for comparisons of baseline characteristics. The Cox's proportional hazard model was used for univariable and multivariable analyses. Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test.\n According to the stage of disease, there were 36 patients with localized disease, 29 patients with initially localized disease but with its recurrence in the period of follow up, and finally, 35 patients had metastatic disease from the very beginning of disease. Tumor originated most commonly in the stomach (41%), small intestine was the second most common location (36%). The mean size of primary tumors was 6.5 cm. The mean duration of follow-up was 60 mo. Multiple parameters were analyzed for their effect on overall survival, but no one reached statistical significance (P = 0.06). Analysis of time to progression/relapse in initially localized disease (univariate analysis), tumor size, mitotic count, Ki-67 and type of d-KIT distribution (cytoplasmic vs membrane/"dot-like") showed statistically significant correlation. In multivariate analysis in the group of patients with localized disease, there were only 2 parameters that have impact on relapse, Ki-67 and SMA (P < 0.0001 and P < 0.034, respectively). Furthermore, Ki-67 was analyzed in localized disease vs localized with recurrence and metastatic disease. It was shown that there is a strict difference between these 2 groups of patients (median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease, P < 0.0001). It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%. The curves for survival on that cut-off level are significantly different (P < 0.04, Cox F).\n Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease.\n\nBrcic, Iva\n\n\n"
},
{
"text": "\n6263\nDeterminants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS).\n\nReeve, J\n\nLunt, M\n\nFelsenberg, D\n\nSilman, AJ\n\nScheidt-Nave, C\n\nPoor, G\n\nGennari, C\n\nWeber, K\n\nLorenc, R\n\nMasaryk, P\n\nCannata, JB\n\nDequeker, J\n\nReid, DM\n\nPols, HA\n\nBenevolenskaya, LI\n\nStepan, JJ\n\nMiazgowski, T\n\nBhalla, A\n\nBruges Armas, J\n\nEastell, R\n\nLopes-Vaz, A\n\nLyritis, G\n\nJajic, I\n\nWoolf, AD\n\nBanzer, D\n\nReisinger, W\n\nTodd, CJ\n\nFelsch, B\n\nHavelka, S\n\nHoszowski, K\n\nJanott, J\n\nJohnell, O\n\nRaspe, HH\n\nYershova, OB\n\nKanis, JA\n\nArmbrecht, G\n\nFinn, JD\n\nGowin, W\n\nO'Neill, TW\n\nEuropean Prospective Osteoporosis Study Group\n\nBeiträge in Fachzeitschriften\nISI:000184943900013\n12968676.0\n10.1359/jbmr.2003.18.9.1664\nNone\nMore severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. INTRODUCTION: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. METHODS: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. RESULTS AND CONCLUSIONS: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n146818\nGuideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM).\n\nBrockow, K\n\nPrzybilla, B\n\nAberer, W\n\nBircher, AJ\n\nBrehler, R\n\nDickel, H\n\nFuchs, T\n\nJakob, T\n\nLange, L\n\nPfützner, W\n\nMockenhaupt, M\n\nOtt, H\n\nPfaar, O\n\nRing, J\n\nSachs, B\n\nSitter, H\n\nTrautmann, A\n\nTreudler, R\n\nWedi, B\n\nWorm, M\n\nWurpts, G\n\nZuberbier, T\n\nMerk, HF\n\nBeiträge in Fachzeitschriften\nNone\n26120552.0\n10.1007/s40629-015-0052-6\nPMC4479479\nDrug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1-6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks-6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an "allergy passport" in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n172263\nMASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.\n\nParati, G\n\nAgabiti-Rosei, E\n\nBakris, GL\n\nBilo, G\n\nBranzi, G\n\nCecchi, F\n\nChrostowska, M\n\nDe la Sierra, A\n\nDomenech, M\n\nDorobantu, M\n\nFaria, T\n\nHuo, Y\n\nJelaković, B\n\nKahan, T\n\nKonradi, A\n\nLaurent, S\n\nLi, N\n\nMadan, K\n\nMancia, G\n\nMcManus, RJ\n\nModesti, PA\n\nOchoa, JE\n\nOctavio, JA\n\nOmboni, S\n\nPalatini, P\n\nPark, JB\n\nPellegrini, D\n\nPerl, S\n\nPodoleanu, C\n\nPucci, G\n\nRedon, J\n\nRenna, N\n\nRhee, MY\n\nRodilla Sala, E\n\nSanchez, R\n\nSchmieder, R\n\nSoranna, D\n\nStergiou, G\n\nStojanovic, M\n\nTsioufis, K\n\nValsecchi, MG\n\nVeglio, F\n\nWaisman, GD\n\nWang, JG\n\nWijnmaalen, P\n\nZambon, A\n\nZanchetti, A\n\nZhang, Y\n\nBeiträge in Fachzeitschriften\nISI:000455309300015\n30573476.0\n10.1136/bmjopen-2017-021038\nPMC6303603\nMasked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM.\n MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed.\n MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal.\n NCT02804074; Pre-results.\n © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nPerl, Sabine\n\n\n"
},
{
"text": "\n175901\nNutritional Lifestyle Intervention in Obese Pregnant Women, Including Lower Carbohydrate Intake, Is Associated With Increased Maternal Free Fatty Acids, 3-β-Hydroxybutyrate, and Fasting Glucose Concentrations: A Secondary Factorial Analysis of the European Multicenter, Randomized Controlled DALI Lifestyle Intervention Trial.\n\nHarreiter, J\n\nSimmons, D\n\nDesoye, G\n\nCorcoy, R\n\nAdelantado, JM\n\nDevlieger, R\n\nGaljaard, S\n\nDamm, P\n\nMathiesen, ER\n\nJensen, DM\n\nAndersen, LLT\n\nDunne, F\n\nLapolla, A\n\nDalfra, MG\n\nBertolotto, A\n\nWender-Ozegowska, E\n\nZawiejska, A\n\nMantaj, U\n\nHill, D\n\nJelsma, JGM\n\nSnoek, FJ\n\nLeutner, M\n\nLackinger, C\n\nWorda, C\n\nBancher-Todesca, D\n\nScharnagl, H\n\nvan Poppel, MNM\n\nKautzky-Willer, A\n\nBeiträge in Fachzeitschriften\nISI:000476786200009\n31182492.0\n10.2337/dc19-0418\nNone\nIn our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism.\n Obese pregnant women (n = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE (n = 221) versus no HE (n = 215) and PA (n = 218) versus no PA (n = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters.\n At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, P < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, P < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, P < 0.05) and 3-β-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, P < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, P = 0.01).\n HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization.\n © 2019 by the American Diabetes Association.\n\nDesoye, Gernot\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n154492\nIdentification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies.\n\nNeurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Stroke Genetics Network (SiGN), and the International Stroke Genetics Consortium (ISGC)\n\nBeiträge in Fachzeitschriften\nISI:000376549300019\n27068588.0\n10.1016/S1474-4422(16)00102-2\nPMC4943223\nGenetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies.\n For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants.\n We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel disease-in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2-32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a) are expressed in brain pericytes and mutant foxf2b(-/-) cerebral vessels show decreased smooth muscle cell and pericyte coverage.\n We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms.\n NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq.\n Copyright © 2016 Elsevier Ltd. All rights reserved.\n\nSchmidt, Reinhold\n\n\n"
}
]
}