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"text": "\n13543\nViridans streptococci in endocarditis and neutropenic sepsis: biofilm formation and effects of antibiotics.\n\nPresterl, E\n\nGrisold, AJ\n\nReichmann, S\n\nHirschl, AM\n\nGeorgopoulos, A\n\nGraninger, W\n\nBeiträge in Fachzeitschriften\nISI:000226309100007\n15563519.0\n10.1093/jac/dkh479\nNone\nViridans group streptococci (VGS) are a frequent cause of bacterial endocarditis or sepsis in patients with neutropenia. Endocarditis in particular, is associated with plaque formation on the endocardium and valve leaflets whereas VGS septicaemia in neutropenic patients is caused by the influx of oral flora bacteria through mucositic lesions. This study examined the in vitro potency for biofilm formation of clinical VGS bloodstream isolates, and the effects of antibiotics on these biofilms.\n During the years 1998-2000, 40 VGS bloodstream isolates from 18 patients with endocarditis and 22 patients with severe sepsis and neutropenia were collected. The MICs of penicillin, teicoplanin and moxifloxacin were determined using the microdilution broth method according to NCCLS criteria. Biofilms were grown in microtitre plates, dyed with Crystal Violet, and the mean optical density (OD) was used for quantification. Biofilms were incubated with penicillin, teicoplanin and moxifloxacin at various concentrations starting with the MICs for the respective isolates tested.\n Isolates from eight out of 18 patients with endocarditis and six out of 22 patients with neutropenia formed biofilms (not significant). For the 14 isolates, the MIC(90)s (range) of penicillin, teicoplanin and moxifloxacin were 0.5 mg/L (0.001-0.5), 0.125 mg/L (0.025-0.125) and 0.5 mg/L (0.05-0.5), respectively. Generally, biofilms persisted although incubated with the antibiotics up to concentrations of 128 x MIC. However, the ODs of biofilms after incubation with an antibiotic were significantly lower than the ODs of biofilms without antibiotic (P<0.05). A significant decrease in the biofilms with increasing antibiotic concentrations was observed for teicoplanin and moxifloxacin, but not for penicillin G.\n VGS isolated from patients with endocarditis and patients with sepsis and neutropenia form biofilms. Biofilms persist even when exposed to antibiotics at concentrations up to 128 x MIC. Nevertheless, teicoplanin and moxifloxacin reduced the density of the biofilms at concentrations >/=16 x MIC. Thus, testing the effects of antibiotics on biofilms may supply useful information in addition to standard in vitro testing, particularly in diseases where biofilm formation is involved in the pathogenesis.\n\nGrisold, Andrea\n\n\n"
},
{
"text": "\n86477\nBone density after teriparatide in patients with or without prior antiresorptive treatment: one-year results from the EUROFORS study.\n\nMinne, H\n\nAudran, M\n\nSimões, ME\n\nObermayer-Pietsch, B\n\nSigurðsson, G\n\nMarín, F\n\nDalsky, GP\n\nNickelsen, T\n\nEUROFORS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000261128700012\n18838053.0\n10.1185/03007990802466595\nNone\nObjective: Recombinant teriparatide, a bone anabolic agent, is given to treatment-naive and pre-treated patients with severe osteoporosis, but few data exist comparing the response to teriparatide in these groups. EUROFORS (the EUROpean study of FORSteo double dagger) enrolled postmenopausal women with established osteoporosis who were either treatment-naive or had prior antiresorptive (AR) treatment with or without documented inadequate clinical response. The objective of the secondary analysis described here was to evaluate the interim bone mineral density (BMD) response in these groups after one year of open-label teriparatide therapy. Research design and methods: Postmenopausal women with established osteoporosis who enrolled in a prospective, randomized, controlled trial received open-label teriparatide 20 mu g/day for the first year. With respect to their prior osteoporosis treatment history, they were retrospectively allocated to one of three groups: treatment-naive (n = 204), prior treatment with an antiresorptive drug (AR-pretreated) (n = 240), or prior antiresorptive treatment with inadequate response (inadequate AR-responders) (n = 421). BMD was measured by dual energy x-ray absorptiometry. Results: Lumbar spine BMD increased from baseline (p < 0.001) in the three groups (mean, 95% CI); treatment-naive: 8.4% (7.4%, 9.3%); AR-pretreated: 7.1% (6.3%, 7.9%); inadequate AR-responders: 6.2% (5.6%, 6.9%). Total hip BMD increased from baseline in the treatment-naive (p < 0.001): 1.8% (1.1%, 2.5%) but did not change in the AR-pretreated: 0.4% (-0.2%, 1.1%) or inadequate AR-responders: -0.3% (-0.9%, 0.2%). Treatment-emergent adverse events were similar in the three groups. Conclusion: One year of teriparatide significantly (p < 0.001) increased spine BMD in all groups, and total hip BMD in the treatment-naive group. Because of the limitations of this interim analysis (most importantly, the short duration of treatment and lack of a control group), further study is needed to determine the optimal treatment duration to reach the potential BMD gains at the proximal femur in patients with prior antiresorptive drug use (mostly bisphosphonates).\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n112158\nTotal body skin examination for skin cancer screening in patients with focused symptoms.\n\nArgenziano, G\n\nZalaudek, I\n\nHofmann-Wellenhof, R\n\nBakos, RM\n\nBergman, W\n\nBlum, A\n\nBroganelli, P\n\nCabo, H\n\nCaltagirone, F\n\nCatrical, C\n\nCoppini, M\n\nDewes, L\n\nFrancia, MG\n\nGarrone, A\n\nTurk, BG\n\nGhigliotti, G\n\nGiacomel, J\n\nGourhant, JY\n\nHlavin, G\n\nKukutsch, N\n\nLipari, D\n\nMelchionda, G\n\nOzdemir, F\n\nPellacani, G\n\nPellicano, R\n\nPuig, S\n\nScalvenzi, M\n\nSortino-Rachou, AM\n\nVirgili, AR\n\nKittler, H\n\nBeiträge in Fachzeitschriften\nISI:000300031100004\n21757257.0\n10.1016/j.jaad.2010.12.039\nNone\nBACKGROUND: The value of total body skin examination (TBSE) for skin cancer screening is controversial. OBJECTIVE: We sought to determine whether TBSE could be helpful in patients with focused skin symptoms who would not otherwise have undergone TBSE. METHODS: In a prospective, multicenter, cross-sectional study consecutive adult patients were recruited during a period of 18 months. Physicians first inspected problem areas and uncovered areas and then performed TBSE. Equivocal lesions detected in both steps were excised or biopsied. Primary outcomes were the absolute and relative risks of missing skin cancer and the number of patients needed to examine to detect melanoma or another malignancy. A secondary outcome was the proportion of false-positive results obtained by TBSE. RESULTS: We examined 14, 81 patients and detected 40 (0.3%) patients with melanoma and 299 (2.1%) with at least one nonmelanoma skin cancer by TBSE. In 195 (1.3%) patients equivocal lesions found by TBSE turned out to be benign. We calculated that 47 patients need to be examined by TBSE to find one skin malignancy and 400 patients to detect one melanoma. The risk of missing one malignancy if not performing TBSE was 2.17% (95% confidence interval 1.25-3.74). Factors significantly increasing the chance to find a skin cancer were age, male gender, previous nonmelanoma skin cancer, fair skin type, skin tumor as the reason for consultation, and presence of an equivocal lesion on problem/uncovered areas. LIMITATIONS: The impact of TBSE on skin cancer mortality was not evaluated. CONCLUSIONS: TBSE improves skin cancer detection in patients with focused skin symptoms and shows a low rate of false-positive results. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.\n\nHofmann-Wellenhof, Rainer\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n117026\nExpression of Ezrin, MMP-9, and COX-2 in 50 Chordoma Specimens: A Clinical and Immunohistochemical Analysis.\n\nFroehlich, EV\n\nScheipl, S\n\nLazary, A\n\nVarga, PP\n\nSchmid, C\n\nStammberger, H\n\nBeham, A\n\nBodo, K\n\nSchroettner, H\n\nQuehenberger, F\n\nWindhager, R\n\nLiegl, B\n\nLeithner, A\n\nBeiträge in Fachzeitschriften\nISI:000304766600001\n22228328.0\n10.1097/BRS.0b013e31824782e1\nNone\nStudy Design. Retrospective study. Objective. To investigate the immunohistochemical expression profile of ezrin, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX)-2 in chordomas. Summary of Background Data. Ezrin, MMP-9, and COX-2 are expressed in different solid tumors, including chordomas. This study investigates the immunohistochemical expression of the aforementioned biomarkers and the clinical outcome in regard to immunohistochemistry, tumor volume, and localization. Methods. Fifty brachyury-verified chordoma specimens of 34 primary and 16 recurrent tumors of 44 patients were tested for ezrin, MMP-9, and COX-2 as possible therapeutical targets by immunohistochemistry. The clinical evaluation concentrated on tumor location, volume, and age-related data. Results. Ezrin expression was detected in 33 of 34 primary chordomas and in 16 of 16 recurrent cases. The primary chordomas located in the sacrum and the spine demonstrated a significantly higher percentage of positively stained tumor cells (P = 0.034) than the skull-based chordomas. An expression of MMP-9 and COX-2 was observed in 33 of 34 primary chordomas and in 16 of 16 recurrences, and in 13 of 34 primary chordomas and in 11 of 16 recurrences, respectively. Patients' survival was significantly influenced by age (P = 0.01), tumor location (P = 0.029), and tumor volume (P = 0.002). A signifi cant positive correlation between tumor volume and the anatomic distance of the chordoma from the skull was calculated (P = 0.00002). Conclusion. En bloc resection with tumor-free margins is seldom feasible, particularly in the sacrum. Intralesional excisions mostly end in early local recurrence; therefore, the demand for further treatment options is frequently posed. The marked trend of the investigated biomarkers of this study may build a starting point for further investigations as molecular targets for future adjuvant therapies in chordomas. Future multicenter studies on larger patients' series are necessary to elucidate these preliminary data and to test new treatment options for patients with chordomas.\n\nBeham-Schmid, Christine\n\nLeithner, Andreas\n\nLiegl-Atzwanger, Bernadette\n\nQuehenberger, Franz\n\nScheipl, Susanne\n\n\n"
},
{
"text": "\n118823\nThe use of Suprathel(®) in deep dermal burns: first results of a prospective study.\n\nKeck, M\n\nSelig, HF\n\nLumenta, DB\n\nKamolz, LP\n\nMittlböck, M\n\nFrey, M\n\nBeiträge in Fachzeitschriften\nISI:000302426600011\n22078803.0\n10.1016/j.burns.2011.09.026\nNone\nIntroduction: While autologous skin grafting has been the standard for coverage of full-thickness areas, several options for deep-partial-thickness defects exist. With regard to economising donor sites, we compared a copolymer based on DL-lactid acid (Suprathel (R)) as temporary wound dressing with autologous skin, and analysed time to healing and scar quality in matched areas of deep-partial-thickness burn. Methods: We recruited 18 patients with a median age of 45 years (range: 25-83 years), for this prospective, non-blinded controlled non-inferiority study, suffering from deep-partial-thickness burns from November 2009 to July 2010. After early tangential excision, matched deep-partial-thickness areas were covered with 1:1.5 meshed autologous skin grafts and the copolymer for direct intra-individual comparison. Scars were evaluated by means of the Vancouver Scar Scale (VSS), the Patient and Observer Scar Assessment Scale (POSAS) and suction cutometry (MPA 580, Courage and Khazaka Electronic GmbH, Cologne, Germany) on days 30 and 90, postoperatively. Results: Fifteen days after surgery, complete wound closure was present in 44.4% (8/18) of all areas covered with copolymer and 88.9% (16/18) in the split-thickness skin graft (STSG) area (p = 0.008). Evaluation of the total VSS, POSAS and cutometry satisfied the criterion of non-inferiority for Suprathel (R) on day 30. Ninety days after surgery, only the Observer Scar Scale showed that Suprathel is non-inferior to STSG, albeit the mean total VSS and Patient Scar Scale were better in Suprathel (R) areas. Conclusion: Suprathel (R) represents a solid, reliable epidermal skin substitute with longer healing times in comparison to skin grafts but comparable results concerning early scar formation. Suprathel (R) can serve as a tool in treatment portfolio for adult patients suffering from deep dermal burns. Especially in patients with extensive burns, Suprathel (R) can be used to cover the deep dermal burn wounds to save STSGs and its donor sites for the coverage of full-thickness burned areas. (C) 2011 Elsevier Ltd and ISBI. All rights reserved.\n\nKamolz, Lars-Peter\n\nLumenta, David Benjamin\n\n\n"
},
{
"text": "\n131462\nLiposomes coated with thiolated chitosan enhance oral peptide delivery to rats.\n\nGradauer, K\n\nBarthelmes, J\n\nVonach, C\n\nAlmer, G\n\nMangge, H\n\nTeubl, B\n\nRoblegg, E\n\nDünnhaupt, S\n\nFröhlich, E\n\nBernkop-Schnürch, A\n\nPrassl, R\n\nBeiträge in Fachzeitschriften\nISI:000328492800030\n24140721.0\n10.1016/j.jconrel.2013.10.011\nPMC3913890\nThe aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan-thioglycolic acid (CS-TGA) or an S-protected version of the same polymer (CS-TGA-MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately -40 mV to a maximum value of about +44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS-TGA-MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS-TGA-coated liposomes or CS-TGA-MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6h, was achieved for CS-TGA-MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS-TGA-MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin.\n © 2013. Published by Elsevier B.V. All rights reserved.\n\nAlmer, Gunter\n\nFröhlich, Eleonore\n\nMangge, Harald\n\nPrassl, Ruth\n\n\n"
},
{
"text": "\n135053\nSuramin analogues as subtype-selective G protein inhibitors.\n\nFreissmuth, M\n\nBoehm, S\n\nBeindl, W\n\nNickel, P\n\nIjzerman, AP\n\nHohenegger, M\n\nNanoff, C\n\nBeiträge in Fachzeitschriften\nISI:A1996UD68900004\n8609887.0\nNone\nNone\nG protein alpha subunits expose specific binding sites that allow for the sequential, conformation-dependent binding of protein reaction partners, e.g., G protein beta gamma dimers, receptors, and effectors. These domains represent potential sites for binding of low-molecular-weight inhibitors. We tested the following suramin analogues as G protein antagonists: 8-(3-nitrobenzamido)-1, , -naphtalenetrisulfonic acid (NF007), 8-(3-(3-nitrobenzamido)benzamido)-1, , -naphtalenetrisulfonic++ + acid NF018), 8, '-(carbonylbis(imino-3, -phenylene))bis-(1, , -naphtalenetri sulfonic acid) (NF023), 8, '-(carbonylbis(imino-3, -phenylene)carbonylimino-(3, -phe nylene))bis-(1, , 5-naphtalenetrisulfonic acid) (NF037), and suramin. The compounds suppressed [35S]GTPgammaS binding to purified, recombinant G protein alpha subunits, an effect that is due to inhibition of GDP release. Suramin is selective for recombinant Gsalpha-s (EC50 values o f approximately 240 nM; rank order of potency, suramin > NF037 > NF023 > NF018 > NF007), whereas NF023 is selective for recombinant Gi alpha-1 and recombinant Go alpha (EC50 value of approximately 300 nM; rank order of potency, NF023 > / = NF037 > suramin >0 NF018 > NF007). Selectivity was also demonstrated on a cellular level. In rat sympathetic neurons, alpha-2-adrenergic and muscarinic receptor-dependent inhibition of the voltage-sensitive calcium current is mediated by Gi/Go, whereas inhibition by vasoactive intestinal peptide (VIP) is mediated by Gs. Calcium current inhibition by alpha2-adrenergic and muscarinic receptors was greatly reduced when 100 microM NF023 was applied intracellularly, whereas the response to VIP was unaffected; in contrast, the response to VIP was blunted only with 100 microM suramin in the recording pipette. The suramin analogues do not interfere with the interaction between alpha subunits and G protein beta gamma dimer but compete with binding of the effector. The addition of purified adenylyl cyclase reverses the inhibitory effect of suramin on the rate of [35S]GTPgammaS binding to recombinant Gsalpha-s, indicating direct competition for a common site; similarly, immunoprecipitation by an antibody directed against an epitope of the effector binding site is inhibited by suramin. Our results show that it is possible to design G protein inhibitors that target the effector binding site on the alpha subunits.\n\n\n"
},
{
"text": "\n136639\nSex and body mass index but not CXCL12 801 G/A polymorphism determine the efficacy of hematopoietic cell mobilization: a study in healthy volunteer donors.\n\nLenk, J\n\nBornhauser, M\n\nKramer, M\n\nHölig, K\n\nPoppe-Thiede, K\n\nSchmidt, H\n\nWiesneth, M\n\nSchaefer-Eckart, K\n\nSchlenke, P\n\nPunzel, M\n\nMartin, S\n\nKroschinsky, F\n\nSchmidt, AH\n\nEhninger, G\n\nThiede, C\n\nBeiträge in Fachzeitschriften\nISI:000324975000018\n23891749.0\n10.1016/j.bbmt.2013.07.018\nNone\nAnalyses of healthy donors of granulocyte colony-stimulating factor (G-CSF) mobilized hematopoietic stem and progenitor cells (HSPCs) and of patients undergoing autologous stem cell transplantation have suggested that individuals harboring the CXCL12-A allele mobilize a higher number of CD34 + HSPCs after G-CSF administration. We typed 463 healthy unrelated donors (376 men and 87 women) who had received daily subcutaneous injections at a mean dose of 7.36 ± 1.71 μg/kg G-CSF for 5 days for CXCL12 801 G/A using a real-time PCR assay. Interestingly, the median concentration of mobilized CD34 + cells on day 5 was almost identical in donors with the A-allele (79/μL; range, 11 to 249/μL) and the G/G-group (82/μL; range, 15 to 268/μL). In addition, the allelic distribution was not different in donors (n = 11) who mobilized less than 20/μL CD34 + cells. No difference in the overall yield of CD34 + cells in the apheresis product and in the number of CD34 + cells/kg recipient could be detected between both groups. In a multivariate regression model for the endpoint CD34 + cells/μL at day 5, only male sex (regression coefficient, 11.5; 95% confidence interval, 1.7 to 21.2, P = .021) and body mass index as continuous variables (regression coefficient, 3.5; 95% confidence interval, 2.5 to 4.5, P = .0001) but not age, smoking status, or CXCL12 allelic status represented independent variables. Our data derived from a large well-controlled cohort contradict previous analyses suggesting an association between CXCL12 allelic status and the yield of CD34 + HSPC after G-CSF mobilization. Concentration of CD34 + cells in the peripheral blood, the most objective parameter, could not be predicted by CXCL12 genotype.\n Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.\n\nSchlenke, Peter\n\n\n"
},
{
"text": "\n152446\nHigh-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration.\n\nPertl, L\n\nKern, S\n\nWeger, M\n\nHausberger, S\n\nTrieb, M\n\nGasser-Steiner, V\n\nHaas, A\n\nScharnagl, H\n\nHeinemann, A\n\nMarsche, G\n\nBeiträge in Fachzeitschriften\nISI:000376588600068\n27171197.0\n10.1371/journal.pone.0154397\nPMC4865135\nHigh-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.\n Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.\n In our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01).\n The investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.\n\nHaas, Anton\n\nHeinemann, Akos\n\nMarsche, Gunther\n\nPinter-Hausberger, Silke\n\nPosch-Pertl, Laura\n\nScharnagl, Hubert\n\nWeger, Martin\n\n\n"
},
{
"text": "\n155878\nEffects of hemodynamic instability on brain death-induced prepreservation liver damage.\n\nGolling, M\n\nMehrabi, A\n\nBlum, K\n\nJahnke, C\n\nKellner, H\n\nBud, O\n\nHashemi, B\n\nBreitkreutz, R\n\nBecker-Brandenburg, K\n\nSchemmer, P\n\nGebhard, MM\n\nHerfarth, C\n\nKraus, T\n\nBeiträge in Fachzeitschriften\nISI:000182573100024\n12717195.0\n10.1097/01.TP.0000062868.34247.8F\nNone\nBrain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD.\n BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver).\n Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01).\n During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n161808\nPrognostic significance of Fuhrman grade and age for cancer-specific and overall survival in patients with papillary renal cell carcinoma: results of an international multi-institutional study on 2189 patients.\n\nBorgmann, H\n\nMusquera, M\n\nHaferkamp, A\n\nVilaseca, A\n\nKlatte, T\n\nShariat, SF\n\nScavuzzo, A\n\nJimenez Rios, MA\n\nWolff, I\n\nCapitanio, U\n\nDell'Oglio, P\n\nKrabbe, LM\n\nHerrmann, E\n\nEcke, T\n\nVergho, D\n\nHuck, N\n\nWagener, N\n\nPahernik, S\n\nZastrow, S\n\nWirth, M\n\nSurcel, C\n\nMirvald, C\n\nProchazkova, K\n\nHutterer, G\n\nZigeuner, R\n\nCindolo, L\n\nHora, M\n\nStief, CG\n\nMay, M\n\nBrookman-May, SD\n\nBeiträge in Fachzeitschriften\nISI:000415833400011\n28836063.0\n10.1007/s00345-017-2078-5\nNone\nBecause the prognostic impact of the clinical and pathological features on cancer-specific survival (CSS) and overall survival (OS) in patients with papillary renal cell carcinoma (papRCC) is still controversial, we want to assess the impact of clinicopathological features, including Fuhrman grade and age, on survival in surgically treated papRCC patients in a large multi-institutional series.\n We established a comprehensive multi-institutional database of surgically treated papRCC patients. Histopathological data collected from 2189 patients with papRCC after radical nephrectomy or nephron-sparing surgery were pooled from 18 centres in Europe and North America. OS and CSS probabilities were estimated using the Kaplan-Meier method. Multivariable competing risks analyses were used to assess the impact of Fuhrman grade (FG1-FG4) and age groups (<50 years, 50-75 years, >75 years) on cancer-specific mortality (CSM).\n CSS and OS rates for patients were 89 and 81% at 3 years, 86 and 75% at 5 years and 78 and 41% at 10 years after surgery, respectively. CSM differed significantly between FG 3 (hazard ratio [HR] 4.22, 95% confidence interval [CI] 2.17-8.22; p < 0.001) and FG 4 (HR 8.93, 95% CI 4.25-18.79; p < 0.001) in comparison to FG 1. CSM was significantly worse in patients aged >75 (HR 2.85, 95% CI 2.06-3.95; p < 0.001) compared to <50 years.\n FG is a strong prognostic factor for CSS in papRCC patients. In addition, patients older than 75 have worse CSM than patients younger than 50 years. These findings should be considered for clinical decision making.\n\nHutterer, Georg\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n165408\nMuscle-invasive bladder cancer is characterized by overexpression of thymidine kinase 1.\n\nRausch, S\n\nHennenlotter, J\n\nTeepe, K\n\nKuehs, U\n\nAufderklamm, S\n\nBier, S\n\nMischinger, J\n\nGakis, G\n\nStenzl, A\n\nSchwentner, C\n\nTodenhöfer, T\n\nBeiträge in Fachzeitschriften\nISI:000377121600009\n26231311.0\n10.1016/j.urolonc.2015.06.007\nNone\nThymidine kinases have an important role in the synthesis of DNA and exhibit high activity in rapidly proliferating cells. Thymidine kinase 1 (TK1) activity has been shown to be increased in various cancer types and proposed as a prognostic parameter. Aim of the present study was to investigate TK1 in muscle-invasive urothelial carcinoma (UC).\n Corresponding UC and benign samples from paraffin embedded tissue of 111 patients treated with cystectomy for invasive UC from 1996 to 2006 were immunohistochemically (IHC) assessed for TK1. IHC expression patterns were evaluated in a semiquantitative fashion by 2 independent reviewers. Localization of staining was categorized into pure nuclear and additional cytoplasmic localization. Uni- and multivariate analyses were performed to assess differential expression in normal and UC tissue and to evaluate the diagnostic and predictive capability of TK1 by correlation to clinical data. To correlate TK1 expression with molecular subtypes of UC, analysis of TK1 RNA expression levels of the Cancer Genome Atlas UC cohort was performed.\n TK1 was significantly overexpressed in invasive UC, compared to benign urothelium (P<0.0001), and cytoplasmic expression was more often found in cancer tissue than in benign tissue (P = 0.0001). No correlations of TK1 protein expression patterns to standard histopathological determinants were detected. In univariate analysis, TK1 nuclear and cytoplasmic expression was associated with improved cancer-specific survival (P = 0.0119). However, only metastasis status and histologic grade were identified as independent predictors of cancer-specific survival in multivariate analysis. TK1 expression was merely found in the basal layers of benign urothelium. RNA overexpression of TK1 could be correlated to the biologically more aggressive basal UC subtype.\n TK1 expression is significantly different in invasive UC and benign urothelium, which underlines its potential as a diagnostic marker. Although TK1 is considered to be a marker of proliferation, and TK1 RNA overexpression is associated with an aggressive UC subtype, its capability as a predictive IHC biomarker for invasive UC remains limited.\n Copyright © 2015 Elsevier Inc. All rights reserved.\n\n\n"
},
{
"text": "\n176381\nInternational management platform for children's interstitial lung disease (chILD-EU).\n\nGriese, M\n\nSeidl, E\n\nHengst, M\n\nReu, S\n\nRock, H\n\nAnthony, G\n\nKiper, N\n\nEmiralioğlu, N\n\nSnijders, D\n\nGoldbeck, L\n\nLeidl, R\n\nLey-Zaporozhan, J\n\nKrüger-Stollfuss, I\n\nKammer, B\n\nWesselak, T\n\nEismann, C\n\nSchams, A\n\nNeuner, D\n\nMacLean, M\n\nNicholson, AG\n\nLauren, M\n\nClement, A\n\nEpaud, R\n\nde Blic, J\n\nAshworth, M\n\nAurora, P\n\nCalder, A\n\nWetzke, M\n\nKappler, M\n\nCunningham, S\n\nSchwerk, N\n\nBush, A\n\nthe other chILD-EU collaborators\n\nBeiträge in Fachzeitschriften\nISI:000426753500007\n29056600.0\n10.1136/thoraxjnl-2017-210519\nNone\nChildren's interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register.Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases.\n A web-based chILD management platform with a registry and biobank was successfully designed and implemented.\n Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%).The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the 'wrong' answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation.\n We have shown that chILD-EU has generated a platform to help the clinical assessment of chILD.\n Results, NCT02852928.\n © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.\n\nEber, Ernst\n\nPfleger, Andreas\n\n\n"
},
{
"text": "\n182844\nRecipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased <i>Lactobacillus</i> Abundance in the Human Gut Microbiome.\n\nButler, MI\n\nBastiaanssen, TFS\n\nLong-Smith, C\n\nBerding, K\n\nMorkl, S\n\nCusack, AM\n\nStrain, C\n\nBusca, K\n\nPorteous-Allen, P\n\nClaesson, MJ\n\nStanton, C\n\nCryan, JF\n\nAllen, D\n\nDinan, TG\n\nBeiträge in Fachzeitschriften\nISI:000542272700318\n32438623.0\n10.3390/nu12051468\nPMC7285075\nThe gut microbiota plays a role in gut-brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm.\n Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured.\n Relative abundance of the genus Lactobacillus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut-brain module approach.\n While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, Lactobacillus, in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as Lactobacillus, which are recognised as being beneficial for a range of physical and mental health outcomes.\n\nMörkl, Sabrina\n\n\n"
},
{
"text": "\n182887\nInternational real-world study of DLL3 expression in patients with small cell lung cancer.\n\nRojo, F\n\nCorassa, M\n\nMavroudis, D\n\nÖz, AB\n\nBiesma, B\n\nBrcic, L\n\nPauwels, P\n\nSailer, V\n\nGosney, J\n\nMiljkovic, D\n\nHader, C\n\nWu, M\n\nAlmarez, T\n\nPenault-Llorca, F\n\nBeiträge in Fachzeitschriften\nISI:000571476500010\n32745892.0\n10.1016/j.lungcan.2020.07.026\nNone\nExpression of the Notch-family ligand delta-like protein 3 (DLL3), a potential therapeutic target in small cell lung cancer (SCLC), has not been assessed in the real-world setting. To identify the real-world utility of DLL3 as an SCLC therapeutic target, we performed the largest retrospective international noninterventional study to date to evaluate DLL3 prevalence in SCLC patients.\n DLL3 expression was assessed using immunohistochemistry in archived histological and cytological specimens (independent and paired) and correlated to patient demographics, clinical disease characteristics, and survival. The primary endpoint was the proportion of patients with DLL3 expression in ≥25 % of tumor cells. DLL3 expression concordance was assessed in paired specimens.\n Independent tumor specimens were collected from 1073 patients. The mean age at biopsy was 66 years (SD, 10); 682 (64 %) patients were male. Paired specimens were collected from 36 patients. The mean age at biopsy was 62 years (SD, 11); 16 (44 %) patients were male. Most patients had ECOG performance status of 0-1, were smokers/ex-smokers, and received ≥1 prior therapy. Positive DLL3 expression (defined as ≥25 % of tumor cells) was identified in 895/1050 (85 %) patients with 1 specimen and evaluable DLL3 expression; 719/1050 (68 %) patients had high DLL3 expression (defined as ≥75 % of tumor cells). DLL3 expression concordance was 88 % between paired specimens (n = 17; Cohen's kappa P value, .9412). There was no significant difference in median overall survival from SCLC diagnosis for evaluable patients with nonmissing data based on DLL3 expression (negative DLL3 expression [n = 139], 9.5 months; positive DLL3 expression [n = 747], 9.5 months; all evaluable patients [n = 893, 9.5 months).\n These real-world epidemiologic findings indicate that DLL3 is robustly expressed across SCLC disease stages and remains stable despite treatment, consistent with available clinical trial data. There was no prognostic role for DLL3 observed in this study for overall survival.\n Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.\n\nBrcic, Luka\n\n\n"
},
{
"text": "\n544\nComplications and surgical interventions during 4 years of biliary extracorporeal shockwave lithotripsy.\n\nSchreiber, F\n\nSteindorfer, P\n\nPristautz, H\n\nGurakuqi, GC\n\nSchnedl, W\n\nTrauner, M\n\nBeiträge in Fachzeitschriften\nISI:A1996VP41800009\n8908539.0\nNone\nNone\nExtracorporeal shockwave lithotripsy (ESWL) of renal concrements, a revolutionary therapeutic concept, was introduced into clinical routine in the early 1980s. In this study, complications and surgical interventions of biliary extracorporeal shockwave lithotripsy were investigated.\n Two hundred-eighty patients with gallbladder stones underwent extracorporeal shockwave lithotripsy during a 4 year (January 1990-December 1993) investigation period. Two hundred four patients were female, and 76 patients were male with a mean age of 48 years. All patients were symptomatic. Selection was carried out following the "Munich criteria" and the selection rate was 15.3% of all referred patients (n = 1831). One hundred eighty-eight patients had solitary stones, 92 patients presented with multiple stones (maximum 3 stones), with an average of 1.7 stones and a mean stone volume of 2.4 cm3 and stone diameter of 16.5 mm. Shockwave lithotripsy was performed with a second generation electrohydraulic lithotriptor with a mean of 2.1 sessions. Mean duration of one session was 50 min, 1331 discharges were applied on average with a mean power of 22.7 kV.\n Analgesia, with Alfetanil (mean 2.3 mg), was necessary in 68% of all treatment sessions. Fragmentation could be achieved in 81% of the cases, stone clearance was observed in 172 cases (66.4%) out of 258 patients after 12 months. Twenty-two patients were treated in 1993 and are still under observance. Side effects such as colic after treatment were observed in 88 cases (31.4%). In seven cases, severe complications such as impaction of fragments in the papilla of Vater followed by serochemical pancreatitis were seen. An urgent endoscopic sphincterotomy was necessary in these 7 cases (2.5%). Within 4 weeks after shockwave treatment in 4 cases 1.4% emergency cholecystenomy had to be performed. Elective cholecystectomy was done in 16 patients (5.7%). There were no deaths observed during the investigation period.\n Based on the results of our series, we do not recommend biliary ESWL in patients with stone volumes exceeding 14 cm3 (3cm), the high fragment volume after sufficient fragmentation by shockwaves indicates long term oral dissolution therapy. The probability of complications will be increased by the presence of larger fragments.\n\n\n"
},
{
"text": "\n2630\nThe structure of the mouse lipoprotein lipase gene: a B1 repetitive element is inserted into the 3' untranslated region of the mRNA.\n\nZechner, R\n\nNewman, TC\n\nSteiner, E\n\nBreslow, JL\n\nBeiträge in Fachzeitschriften\nISI:A1991GA48800008\n1765386.0\n10.1016/0888-7543(91)90102-K\nNone\nThe catabolism of triglycerides-rich lipoproteins and the subsequent uptake of free fatty acids by muscle and adipose tissue is dependent on the enzyme lipoprotein lipase (LPL). To better understand the regulation of this enzyme, we have isolated and characterized the mouse LPL gene. The gene is 28 kb in length and comprises 10 exons which encode a 4.0-kb mRNA. In this report, almost 6 kb of DNA sequence is presented, including 1251 bp 5' to the gene, over 4 kb of exon and exon-intron junctions, and 583 bp 3' to the gene. RNA from differentiated 3T3-L1 adipocytes was used in primer extension and RNase protection assays to show that the 5' untranslated region is not interrupted by an intron and the start site of transcription is 199 bp 5' to the ATG codon that begins translation. The first exon codes for the 5' untranslated region and the signal peptide of 27 amino acids and 2 amino acids of the mature protein, exons 2-9 code for 445 amino acids of the mature protein. These exons are short and vary in length from 102 to 287 bp. The 10th exon codes for the 3' untranslated region and is 2346 bp long. This exon contains a single copy of a B1 repetitive element of 152 bp followed by a 169-bp homopurine stretch. These elements are flanked by a pair of 16-bp direct repeats. The mouse gene is similar in size to the human, which also contains 10 exons in similar locations. There is a high degree of sequence homology between the two genes, 5' region (700 bp), 75%; 5' untranslated region, 74%; coding region, 88%; 3' untranslated region, 75%. The most striking difference is the absence of the B1 repetitive element and homopurine region in the human 3' untranslated region. This information about the mouse LPL gene may lead to a better understanding of its regulation and role in plasma lipoprotein metabolism.\n\n\n"
},
{
"text": "\n3558\nDermoscopic criteria for melanoma in situ are similar to those for early invasive melanoma.\n\nPizzichetta, MA\n\nArgenziano, G\n\nTalamini, R\n\nPiccolo, D\n\nGatti, A\n\nTrevisan, G\n\nSasso, G\n\nVeronesi, A\n\nCarbone, A\n\nSoyer, HP\n\nBeiträge in Fachzeitschriften\nISI:000167348200013\n11251951.0\n10.1002%2F1097-0142%2820010301%2991%3A5%3C992%3A%3AAID-CNCR1089%3E3.0.CO%3B2-I\nNone\nBACKGROUND: Dermoscopy is a noninvasive technique that increases the diagnostic accuracy of pigmented skin lesions, particularly improving the diagnosis of patients with cutaneous melanoma in situ (CMIS) and early invasive melanoma. To establish reliable and reproducible dermoscopic criteria for the diagnosis of CMIS, the authors conducted a retrospective clinical study of 37 patients with CMIS and 53 patients with invasive cutaneous melanomas (ICM). METHODS: The 37 patients with CMIS were divided into three groups: those with CMIS lesions measuring < or = 5 mm in greatest dimension (8 patients), those with CMIS lesions measuring from > 5 mm to < or = 10 mm in greatest dimension (20 patients), and those with CMIS lesions measuring > 10 mm in greatest dimension (9 patients). The 53 patients with ICM were divided into two groups according to Breslow index: those with ICM lesions measuring < or = 0.75 mm in tumor thickness (19 patients) and those with ICM lesions measuring > 0.75 mm in tumor thickness (34 patients). Lesions were examined with a dermatoscope and were photographed at a magnification of x10. Dermoscopic criteria were evaluated from examination of the photomicrographs. RESULTS: Blue-whitish veil, gray-blue areas, black dots, and irregular extensions and branched streaks were the most relevant dermoscopic criteria for CMIS and were present in 78%, 76%, 73%, and 62% of lesions, respectively. Brown globules, irregular pigment network, pseudopods, and depigmentation were present in 57%, 54%, 54%, and 51% of CMIS lesions, respectively. White scar-like areas and linear and/or dotted vascular patterns, two criteria that are associated frequently with ICM, were not found in our patients with CMIS. No clinically significant differences were observed between the three groups of CMIS patients. CONCLUSIONS: Dermoscopic criteria for CMIS were similar to those for ICM, although white scar-like areas and linear and/or dotted vascular patterns were observed only in patients with ICM. Dermoscopic criteria appeared to be independent of CMIS lesions size.\n\n\n"
},
{
"text": "\n53737\nGenotype combinations of plasminogen activator inhibitor-1 and angiotensin-converting enzyme genes and risk for early onset of coronary heart disease.\n\nLoew, M\n\nHoffmann, MM\n\nHahmann, H\n\nMaerz, W\n\nBrenner, H\n\nRothenbacher, D\n\nBeiträge in Fachzeitschriften\nISI:000241026600023\n16926677.0\nNone\nNone\nBACKGROUND: Both angiotensin-converting enzyme genotype and plasminogen activator inhibitor type 1 genotype have an effect on fibrinolytic components and hence, may increase risk or advance occurrence of coronary heart disease. We examined the association of the angiotensin-converting enzyme and the plasminogen activator inhibitor type 1 genotypes, and their combinations, with early onset of coronary heart disease in a cohort of 907 patients with coronary heart disease. DESIGN AND METHODS: All patients with a coronary heart disease (International Classification of Diseases, 9th Rev. pos. 410-414), aged 30-70 years and participating in an inpatient rehabilitation program between January 1999 and May 2000 in two clinical centres in Germany were enrolled. The plasminogen activator inhibitor type 1 and the angiotensin-converting enzyme genotypes were determined by polymerase chain reaction, and the distribution was compared between patients with early (< or =55 years) and late (>55 years) onset of coronary heart disease. A multivariate analysis was employed to adjust for potentially confounding factors. RESULTS: Of the 907 included patients, 408 (45.0%) developed coronary heart disease before the age of 55 years. For the 4G/4G genotype of plasminogen activator inhibitor type 1 the odds ratio for early onset of coronary heart disease was 1.68 [95% confidence interval (CI) 1.01-2.57] and for the D/D genotype of angiotensin-converting enzyme the odds ratio was 1.22 (95% CI 0.84-1.76) after adjustment for covariates. In multivariate analysis an odds ratio of 3.10 (95% CI 1.51-6.36) was found for the association between the combined homozygosity for both polymorphisms (plasminogen activator inhibitor type 1 genotype 4G/4G and angiotensin-converting enzyme genotype D/D) and onset of coronary heart disease before the age of 55 years after controlling for sex, age, smoking, diabetes, hypertension, hyperlipidemia and school education. CONCLUSION: The co-existence of the 4G/5G polymorphism of the plasminogen activator inhibitor type 1 gene and the I/D polymorphism of the angiotensin-converting enzyme gene increases the risk for early onset of coronary heart disease in this population.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n60747\nChromogenic in situ hybridization: a novel approach to a practical and sensitive method for the detection of HER2 oncogene in archival human breast carcinoma.\n\nDandachi, N\n\nDietze, O\n\nHauser-Kronberger, C\n\nBeiträge in Fachzeitschriften\nISI:000177570400005\n12177239.0\n10.1097/01.LAB.0000024360.48464.A4\nNone\nThe high incidence of HER2 overexpression on the cell surface of breast cancer cells and the recognized prognostic and potentially predictive value of HER2 render this cell surface receptor a novel and important therapeutic target. Although immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridization (FISH; PathVysion and INFORM)-both approved by the Food and Drug Administration-have emerged as the most viable assays for evaluation of HER2 status in routine clinical practice, there is still no consensus on which is the best method for assessing HER2 status. Therefore, our specific objective was to establish a chromogenic in situ hybridization (CISH) assay for the detection of HER2 amplification on a cohort of 173 archival invasive breast carcinomas. Results were compared with HercepTest, which is the most frequently used method for detecting HER2 alteration. Additionally, HER2 gene copy number was investigated using differential PCR (dPCR) as a testing system. HER2 overexpression was found by IHC in 24.3%; HER2 amplification was found by CISH in 19.1% and by dPCR in 9.2% of the tumors. The overall concordance rate was 95.9% between CISH and IHC and 85.0% between dPCR and IHC. Kappa statistics revealed an excellent agreement between IHC and CISH (kappa = 0.878), but only a moderate agreement was found between IHC and dPCR (kappa = 0.482). Discrepant cases between CISH and HercepTest and all IHC-positive cases (+2 and +3), a total of 42 cases, were analyzed with the FISH PathVysion (Vysis) assay. Among 25 HercepTest-positive cases (score +3), 2 showed no gene amplification by FISH or CISH. Four of 13 tumors with weak HER2 overexpression (score +2) were negative with both FISH and CISH. Concordance between CISH and FISH was 100% for the 38 cases analyzed. The current study showed that CISH represents a practical and simple assay for evaluating HER2 gene amplification in archival material, offering a promising alternative to IHC or FISH for the routine diagnostic setting.\n\nDandachi, Nadia\n\n\n"
}
]
}