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"text": "\n145174\nMulticenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.\n\nWeber, B\n\nGürtler, L\n\nThorstensson, R\n\nMichl, U\n\nMühlbacher, A\n\nBürgisser, P\n\nVillaescusa, R\n\nEiras, A\n\nGabriel, C\n\nStekel, H\n\nTanprasert, S\n\nOota, S\n\nSilvestre, MJ\n\nMarques, C\n\nLadeira, M\n\nRabenau, H\n\nBerger, A\n\nSchmitt, U\n\nMelchior, W\n\nBeiträge in Fachzeitschriften\nISI:000176159200008\n12037046.0\n10.1128/JCM.40.6.1938-1946.2002\nPMC130745\nFourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody that were available on the international market until now have antigen detection modules with relatively poor sensitivity and produce a higher rate of false-positive results than third-generation enzyme immunoassays (EIAs). The new Cobas Core HIV Combi EIA with an improved sensitivity for HIV p24 antigen was compared to alternative fourth- and third-generation assays, the p24 antigen test, and HIV type 1 (HIV-1) RNA reverse transcriptase PCR (RT-PCR). A total of 94 seroconversion panels (n = 709 sera), samples from the acute phase of infection after seroconversion (n = 32), anti-HIV-1-positive specimens (n = 730) from patients in different stages of the disease, 462 subtyped samples from different geographical locations, anti-HIV-2-positive sera (n = 302), dilutions of cell culture supernatants (n = 62) from cells infected with different HIV-1 subtypes, selected performance panels from Boston Biomedica Inc., 7, 79 unselected samples from blood donors, 303 unselected daily routine samples, 997 specimens from hospitalized patients, and potentially interfering samples (n = 1, 22) were tested with Cobas Core HIV Combi EIA. The new assay showed a sensitivity comparable to that of the Abbott HIV-1 AG Monoclonal A for early detection of HIV infection in seroconversion panels. The mean time delay of Cobas Core HIV Combi EIA (last negative sample plus 1 day) in comparison to that for HIV-1 RT-PCR for 87 panels tested with both methods was 2.75 days. The diagnostic window was reduced with Cobas Core HIV Combi EIA by between 3.6 and 5.7 days from that for third-generation assays. The specificities of Cobas Core HIV Combi EIA in blood donors were 99.84 and 99.85% (after repeated testing). Overall, 30 repeatedly reactive false-positive results out of 10, 31 HIV-negative samples were obtained with Cobas Core HIV Combi EIA. Our results show that a fourth-generation assay with improved specificity such as Cobas Core HIV Combi EIA is suitable for blood donor screening because of its low number of false positives and because it detects HIV p24 antigen with a sensitivity comparable to that of single-antigen assays.\n\n\n"
},
{
"text": "\n146744\nSynthetische Tränen - Ein Schritt näher der menschlichen Tränenflüssigkeit.\n\nHeidinger, A\n\nSchmut, O\n\nWedrich A\n\nBeiträge in Fachzeitschriften\nISI:000359292600003\nNone\n10.1007/s00717-015-0262-9\nNone\nToday it is not possible to synthesize tear substitutes identical to human tears. Beside water and sodium chloride natural tears contain various other components like proteins, lipids, mucins, antioxidants and buffer substances. Tear substitutes which are used for therapy of dry eye syndrome contain little to no of these components. To create tear substitutes identical to human tears an addition of several components of natural tears is necessary. One of these components concerns ingredients with antioxidative potential. Aim of this study is to identify substances with protective function against ultraviolet light and ozone, which could be used in artificial tear substitutes. Furthermore this paper examines physiological components of natural tears for creation of an optimized artificial tear substitute. Viscosity measurements were used to identify substances with protective function against environmental influences. All substances investigated are described in literature as radical scavengers with possible antioxidant function. They were dissolved in accurately defined concentrations in 0.25 % hyaluronic acid solution and irradiated with ultraviolet light or steamed with ozone followed by a viscosity measurement with a KPG-Ubbelohde viscosimeter. Ultraviolet light and ozone lead to a depolymerisation of hyaluronic acid associated with a decrease of viscosity, which can be traced back to the formation of free radicals. A lower decrease of viscosity or no change of viscosity despite irradiation or steaming can be interpreted as protective function of the added substance. Concerning other tear film components a research of actual literature has been summarized. All in all 11 substances with possible protective function against ultraviolet light and ozone were investigated: eyebright and mannitol could significantly protect hyaluronic acid from depolymerisation through influence of ultraviolet light and ozone (p < 0, 5). Uric acid and melatonine were able to achieve a significant effect against ultraviolet light (p < 0, 5), but not against ozone. Arginine, curcumin, fructose, urea, lysine, spermidine and taurine were not able to protect hyaluronic acid from depolymerisation. Sodium chloride, glucose and bicarbonate are tear ingredients with important function in maintaining homeostasis of ocular surface. For creation of an ideal tear substitute a use of natural tear components like sodium chloride, glucose and bicarbonate should be preferred. For maintaining the antioxidative function of tears eyebright and mannitol, could be added. Both substances are capable of preventing hyaluronic acid in tears from depolymerisation through influence of ultraviolet light and ozone. Also hyaluronic acid in artificial tears may be protected and retention time and lubricating effect on the ocular surface may be extended.\n\nWedrich, Andreas\n\n\n"
},
{
"text": "\n6811\nAmelanotic/hypomelanotic melanoma: clinical and dermoscopic features.\n\nPizzichetta, MA\n\nTalamini, R\n\nStanganelli, I\n\nPuddu, P\n\nBono, R\n\nArgenziano, G\n\nVeronesi, A\n\nTrevisan, G\n\nRabinovitz, H\n\nSoyer, HP\n\nBeiträge in Fachzeitschriften\nISI:000222685600009\n15214897.0\n10.1111/j.1365-2133.2004.05928.x\nNone\nBackground Amelanotic malignant melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. It may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions. Objectives To evaluate whether dermoscopy is also a useful technique for the diagnosis of amelanotic/hypomelanotic melanoma (AHM). Methods We conducted a retrospective clinical study of 151 amelanotic/hypomelanotic skin lesions from 151 patients with a mean age of 47 years ( +/- 17.5 SD). Digitized images of amelanotic/hypomelanotic skin lesions were converted to JPEG format and sent by e-mail from the five participating centres. Lesions included 55 amelanotic/hypornelanotic nonmelanocytic lesions (AHNML), 52 amelanotic/hypomelanotic benign melanocytic lesions (AFMML), and 44 AHM, 10 (23%) of which were nonpigmented, truly amelanotic melanomas (AM). The 44 AHM lesions were divided into thin melanomas (TnM) less than or equal to 1 mm (2 9 cases) and thick melanomas (TkM) > 1 mm (15 cases), according to the Breslow index. Five clinical features (elevation, ulceration, shape, borders and colour) as well as 10 dermoscopic criteria (pigment network, pigmentation, streaks, dots/globules, blue-whitish veil, regression structures, hypopigmentation, leaf-like areas, multiple grey-bluish globules, central white patch) and eight vascular patterns (comma, arborizing, hairpin, dotted, linear irregular, dotted and linear irregular vessels, and milky-red areas) were evaluated in order to achieve clinical and dermoscopic diagnoses. Statistical analyses were performed with the chi(2)-test and Fisher's exact test, when appropriate. Results The most frequent and significant clinical features for TnM and TkM were asymmetry and ulceration (the latter only for TkM) compared with AHBML. Irregular dots/globules (62% vs. 35%; P less than or equal to 0.03), regression structures (48% vs. 27%; P less than or equal to 0.03), irregular pigmentation (41% vs. 11%; P less than or equal to 0.03) and blue-whitish veil (10% vs. 0%; P less than or equal to 0.03) were the most relevant dermoscopic criteria for TnM in comparison with AHBML. TkM differed significantly from AHBML in frequency of occurrence of irregular pigmentation (87% vs. 11%; P less than or equal to 0.03), irregular dots/globules (73% vs. 35%; P less than or equal to 0.03), regression structures (67% vs. 27%; P less than or equal to 0.03), blue-whitish veil (27% vs. 0%; P less than or equal to 0.03) and hypopigmentation (13% vs. 55%; P less than or equal to 0.03). Linear irregular vessels and the were diagnosed as either benign melanocytic lesion (four cases) or BCC (two cases).\n\n\n"
},
{
"text": "\n63145\nQuantitative determination of proteins in single cells with amidoblack (author's transl)\n\nSchauenstein, E\n\nDesoye, G\n\nNöhammer, G\n\nBeiträge in Fachzeitschriften\nISI:A1980KF09400010\n7410125.0\n10.1007/BF00498503\nNone\nIn aqueous solution Amido Black B (ASB) forms stable and well-defined complexes with bovine serum albumin (RSA) at pH 5.5. The complexes can be separated by column chromatography. The formation of the complexes consist in a fast reaction during which, after 3 to 5 h approximately, 3 molecules of ASB have been bound per molecule RSA, and of a much slower reaction which, even after a laps of 24 h, is still far from approaching its final stage. With solid films of RSA, after denaturation with ethanol, fast reaction is found to approach its final stage after 10 min reaction time. With these model protein preparations, the molar extinction coefficient of the ASB-protein complexes can be determined: the soluble ASB-RSA complexes can be brought to complete dissociation at pH 12.3. After the additivity of the specific absorptions of both RSA and ASB had been proven, it was possible to determine the content of the solution of ASB and RSA, and therefrom the molar extinction coefficient of the ASB-RSA-complex at Ph 5.5: epsilon 620 = 110, 00. ASB-stained ethanol-fixed RSA films show an epsilon 620 of approximately 96, 00, if their thickness and specific weight are known. After incubation in watery or ethanolic/TCA solutions of ASB, also animal cells fixed with ether-ethanol show the ASB absorption band to be in the region of 600 nm after removal of the surplus of ASB by thorough washings. As already observed with the RSA films, the kinetics of the staining of the cells show the fast reaction reaching its final stage already after 15 to 20 min. When alcoholic solution of ASB is used, the extinctions are found to be twice or three times higher than those achieved by an aqueous one. After standardization of the staining procedures with both solvents the total extinctions of EATZ, YATZ, rat hepatocytes, chicken thymus and bursa cells were measured and plotted against the macroscopically determined protein content of the respective cells. Highly significant positive linear correlations resulted with staining both in watery and alcoholic solutions, respectively. From the slope of the straight lines, specific extinction coefficient of ASB stained cellular proteins could be calculated up to epsilon' 620 = 1.76 with watery ASB solution and epsilon' 620 = 3.83 with the alcoholic solvent. The soluble ASB-RSA complexes have an epsilon' 620 = 1.67 the ASB stained ethanol denaturated films of RSA an epsilon' 620 of within a range of 1.21 to 1.80.\n\nDesoye, Gernot\n\n\n"
},
{
"text": "\n174078\nRisk Factors of Subsequent Primary Melanomas in Austria.\n\nMüller, C\n\nWendt, J\n\nRauscher, S\n\nSunder-Plassmann, R\n\nRichtig, E\n\nFae, I\n\nFischer, G\n\nOkamoto, I\n\nBeiträge in Fachzeitschriften\nISI:000458611700008\n30566178.0\n10.1001/jamadermatol.2018.4645\nPMC6439543\nInformation on risk factors of subsequent melanomas would be helpful to identify patients at risk after the diagnosis of their first melanomas.\n To determine risk factors of subsequent melanomas.\n In this retrospective case-control study, 1648 participants with histologically verified cutaneous melanoma diagnosed from January 1, 1968, though March 16, 2015, were recruited from a tertiary referral center as part of the Molecular Markers of Melanoma study. CDKN2A was sequenced in 514 and MC1R in 953 participants. Data were analyzed from March 7, 2008, through March 25, 2015.\n Phenotypic traits and internal and external risk factors for the development of a second, third, or fourth melanoma.\n In total, 1648 patients (53.6% men; mean [SD] age, 54 [15] years) were enrolled, including 1349 with single and 299 with multiple primary melanoma. Mean (SD) age at recruitment was 57 (15) years for the single-melanoma and 62 (14) years for the multiple-melanoma groups. From the internal risk factors, family history (odds ratio [OR], 1.76; 95% CI, 1.22-2.55; P = .006), CDKN2A high-risk mutations (OR, 4.03; 95% CI, 1.28-12.70; P = .02), and high numbers of nevi as a phenotypic risk factor (ORs, 2.23 [95% CI, 1.56-3.28, P < .001] for 20-30 smaller nevi and 2.56 [95% CI, 1.50-4.36; P = .003] for 20-30 larger nevi) were significantly associated with the risk of developing a subsequent primary melanoma using multivariate logistic regression analysis. Nonmelanoma skin cancer (OR, 2.57; 95% CI, 1.84-3.58; P < .001) and signs of actinic skin damage, particularly on the back (ORs, 1.91 [95% CI, 1.12-3.25; P = .04] for freckling and 1.92 [95% CI, 1.29-3.08; P = .007] for solar lentigines), additionally increased risk of a subsequent melanoma. All those factors were also associated with an earlier development of the second melanoma. Patients with 3 melanomas developed their second melanoma earlier than patients with only 2 melanomas (mean [SD] age, 55 [15] years for those with 2 primary melanomas; 52 [15] years for those with 3 primary melanomas). Time spent outdoors, solarium use, outdoor occupation, and hair color had no significant associations in these models.\n According to the results of this study, internal factors (family history and genetic variants), number of nevi, and actinic damage on the back are more relevant for the development of subsequent melanomas than skin phototype or hair color. Patients with many nevi were younger at the time of the diagnosis of their first melanoma. This finding could help to identify persons at increased risk of developing multiple primary melanomas.\n\nRichtig, Erika\n\n\n"
},
{
"text": "\n161210\nPrevalence of Celiac Disease in 52,721 Youth With Type 1 Diabetes: International Comparison Across Three Continents.\n\nCraig, ME\n\nPrinz, N\n\nBoyle, CT\n\nCampbell, FM\n\nJones, TW\n\nHofer, SE\n\nSimmons, JH\n\nHolman, N\n\nTham, E\n\nFröhlich-Reiterer, E\n\nDuBose, S\n\nThornton, H\n\nKing, B\n\nMaahs, DM\n\nHoll, RW\n\nWarner, JT\n\nAustralasian Diabetes Data Network (ADDN)\n\nT1D Exchange Clinic Network (T1DX)\n\nNational Paediatric Diabetes Audit (NPDA) and the Royal College of Paediatrics and Child Health\n\nProspective Diabetes Follow-up Registry (DPV) initiative\n\nBeiträge in Fachzeitschriften\nISI:000406014200019\n28546222.0\n10.2337/dc16-2508\nPMC6463736\nCeliac disease (CD) has a recognized association with type 1 diabetes. We examined international differences in CD prevalence and clinical characteristics of youth with coexisting type 1 diabetes and CD versus type 1 diabetes only.\n Data sources were as follows: the Prospective Diabetes Follow-up Registry (DPV) (Germany/Austria); the T1D Exchange Clinic Network (T1DX) (U.S.); the National Paediatric Diabetes Audit (NPDA) (U.K. [England/Wales]); and the Australasian Diabetes Data Network (ADDN) (Australia). The analysis included 52, 21 youths <18 years of age with a clinic visit between April 2013 and March 2014. Multivariable linear and logistic regression models were constructed to analyze the relationship between outcomes (HbA1c, height SD score [SDS], overweight/obesity) and type 1 diabetes/CD versus type 1 diabetes, adjusting for sex, age, and diabetes duration.\n Biopsy-confirmed CD was present in 1, 35 youths (3.5%) and was diagnosed at a median age of 8.1 years (interquartile range 5.3-11.2 years). Diabetes duration at CD diagnosis was <1 year in 37% of youths, >1-2 years in 18% of youths, >3-5 years in 23% of youths, and >5 years in 17% of youths. CD prevalence ranged from 1.9% in the T1DX to 7.7% in the ADDN and was higher in girls than boys (4.3% vs. 2.7%, P < 0.001). Children with coexisting CD were younger at diabetes diagnosis compared with those with type 1 diabetes only (5.4 vs. 7.0 years of age, P < 0.001) and fewer were nonwhite (15 vs. 18%, P < 0.001). Height SDS was lower in those with CD (0.36 vs. 0.48, adjusted P < 0.001) and fewer were overweight/obese (34 vs. 37%, adjusted P < 0.001), whereas mean HbA1c values were comparable: 8.3 ± 1.5% (67 ± 17 mmol/mol) versus 8.4 ± 1.6% (68 ± 17 mmol/mol).\n CD is a common comorbidity in youth with type 1 diabetes. Differences in CD prevalence may reflect international variation in screening and diagnostic practices, and/or CD risk. Although glycemic control was not different, the lower height SDS supports close monitoring of growth and nutrition in this population.\n © 2017 by the American Diabetes Association.\n\nFröhlich-Reiterer, Elke\n\n\n"
},
{
"text": "\n181154\nCell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer.\n\nZhou, Q\n\nPerakis, SO\n\nUlz, P\n\nMohan, S\n\nRiedl, JM\n\nTalakic, E\n\nLax, S\n\nTötsch, M\n\nHoefler, G\n\nBauernhofer, T\n\nPichler, M\n\nGerger, A\n\nGeigl, JB\n\nHeitzer, E\n\nSpeicher, MR\n\nBeiträge in Fachzeitschriften\nISI:000517995400001\n32087735.0\n10.1186/s13073-020-0719-6\nPMC7036260\nBevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are largely unknown. Here, we employed whole-genome sequencing of plasma DNA to evaluate the tumor genome of patients undergoing treatment with bevacizumab to determine novel aberrations associated with resistance.\n Using longitudinal plasma analyses, we studied the evolution of tumor genomes in a mCRC cohort (n = 150) and conducted analyses of CRC cases from The Cancer Genome Atlas (TCGA) database (n = 619) to identify associations between genomic aberrations and clinical features. We employed whole-genome sequencing to identify the most frequently occurring focal somatic copy number alterations (SCNAs). Using the TCGA data as a comparative and supporting dataset, we defined the minimally amplified overlapping region and studied the mechanistic consequences of copy number gain of the involved genes in this segment. In addition, we established an in vitro cell model and conducted downstream gene expression and cell viability assays to confirm our findings from the patient dataset.\n We observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of CRC cases from the TCGA database suggested that this amplicon is associated with more advanced stages. We confirmed that this 13q12.2 amplicon frequently emerges later during the clinical course of disease. After defining the minimally amplified region, we observed that the amplification and expression of one gene, POLR1D, impacted cell proliferation and resulted in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab treatment. In fact, in several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with therapy resistance.\n Non-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients.\n\nBauernhofer, Thomas\n\nGeigl, Jochen Bernd\n\nGerger, Armin\n\nHasenleithner, Samantha\n\nHeitzer, Ellen\n\nHöfler, Gerald\n\nPichler, Martin\n\nRiedl, Jakob\n\nSpeicher, Michael\n\nTalakic, Emina\n\nUlz, Peter\n\nZhou, Qing\n\n\n"
},
{
"text": "\n3192\nSynthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone.\n\nel-Shabrawi, Y\n\nEckhardt, M\n\nBerghold, A\n\nFaulborn, J\n\nAuboeck, L\n\nMangge, H\n\nArdjomand, N\n\nBeiträge in Fachzeitschriften\nISI:000088486600020\n11027004.0\n10.1038/eye.2000.92\nNone\nPurpose To determine changes in production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the ciliary body, the trabecular meshwork and the retinal pigment epithelium induced by both prostaglandins and corticosteroids.Methods Explant organ cultures were removed by a scleral incision 3 mm posterior to the limbus. Retinal pigment epithelium was grown to confluence. Organ and cell cultures were treated with latanoprost and/or dexamethasone for 72 h. The activity of MMP-2, -3 and -9 was assessed using zymography. The synthesis pattern of MMPs and TIMP-1 and -2 was identified using immunostaining.Results Treatment of explant organ cultures with 10 mu g/ml of latanoprost induced a mean upregulation of MMP-2 by 36%, MMP-3 by 112% and MMP-9 by 156% as seen by zymography. Dexamethasone 500 nm reduced the amounts of secreted MMP-2 by 13%, MMP-3 by 69%. MMP-9 was not detectable in the media of corticosteroid-treated explant organ cultures. The addition of 10 mu g/ml of latanoprost to dexamethasone-treated cultures increased MMP-2 by 14%, MMP-3 by 43% and MMP-9 by 49%. Using immunohistochemistry we found staining with antibodies against MMP-2, -3, -9 and TIMP-1 and -2 within the ciliary body, and only to a lesser degree in the trabecular meshwork. Latanoprost treatment caused an increase of 29% in MMP-2 (p < 0.0001), 98% in MMP-9 (p < 0.0001) and 108% in MMP-9 (p < 0.0001). Dexamethasone reduced the staining for MMP-2 by 32% (p < 0.0001), for MMP-3 by 33% (p < 0.0001) and for MMP-9 by 83% (p < 0.0001). Almost no change in staining for MMPs was detectable in the trabecular meshwork. Neither latanoprost treatment nor dexamethasone induced significant changes (p < 0.93) in the secretion of TIMPs. In the media of non-treated retinal pigment epithelium (RPE) cells the only MMP detected was MMP-2. RPE cells in culture did not respond to either treatment with a change in their MMP secretion.Conclusion We detected a profound upregulation of both MMP-3 and MMP-9 and a mild induction of MMP-2 through latanoprost in the ciliary body, but not the trabecular meshwork or RPE cells. Corticosteroids, on the other hand, downregulated MMP expression in both tissues. This inhibiting effect of corticosteroids on MMP production was reversed by latanoprost.\n\nArdjomand, Navid\n\nBerghold, Andrea\n\nEl-Shabrawi, Yosuf\n\nMangge, Harald\n\n\n"
},
{
"text": "\n5143\nA single-center experience with retrograde reperfusion in liver transplantation.\n\nKniepeiss, D\n\nIberer, F\n\nGrasser, B\n\nSchaffellner, S\n\nStadlbauer, V\n\nTscheliessnigg, KH\n\nBeiträge in Fachzeitschriften\nISI:000186684300006\n12819865.0\n10.1007/s00147-003-0621-3\nNone\nPoor graft function secondary to injury by ischemia and reperfusion remains a major problem with regard to morbidity and mortality in clinical liver transplantation (LTX). Up to one fifth of patients suffer from poor initial liver function due to severe damage to hepatocytes. This situation leads either to primary nonfunction described in approximately 6% of LTX or to slow recovery. We present a new method of reperfusion during LTX. From July 1998 to July 2002, 42 LTX in 39 recipients, (10 female, 52 years old (26-70) were performed. LTX was carried out in piggy-back technique. After completing the piggy-back anastomosis, the caval vein was declamped immediately, and retrograde low pressure reperfusion of the graft with low oxygenated venous blood was established. Portal anastomosis was performed using a running suture. In order to provide optimal retrograde liver perfusion, no clamping of the donor portal vein was done. After completing portal anastomosis, the recipient portal vein was declamped immediately. During arterial anastomosis, the transplanted liver was antegradely perfused via the portal vein. After completing hepatic artery anastomosis, declamping of the hepatic artery was done and arterial perfusion started. No backtable or in-situ-flushing except the described reperfusion technique was performed. Forty-two LTX in 39 recipients using piggy-back technique and retrograde reperfusion via the caval vein followed by antegrade reperfusion via the portal vein were performed; 38 out of 39 patients (97.44%) were alive and well at day 8 after LTX. One patient (2.56%) died of a pre-existing portal vein thrombosis on day 2 after LTX. Three patients had to undergo retransplantation for hepatic artery thrombosis (7.14%). Liver enzymes, bilirubine, prothrombine time and AT III on day 1, 3, 5 and 8 after LTX showed favourable values. Median aspartate aminotransferase (ASAT) was 219 U/l on day 1 after LTX. One-month survival rate was 95.23%, and 1-year survival rate 87.88%. Two patients died of liver-associated causes (5.12%). One patient died of a late hepatic artery thrombosis, and one more of rejection. No other severe case of rejection appeared. We can conclude that retrograde reperfusion might be highly sufficient method of removing perfusion fluid from the transplanted liver. Low pressure perfusion with low oxygenated blood might reduce the production of free oxygen radicals. Retrograde reperfusion via the caval vein and antegrade reperfusion via the portal vein seemed to lower postoperative liver enzyme values and to improve initial liver function after LTX.\n\nKniepeiss, Daniela\n\nSchaffellner, Silvia\n\nStadlbauer-Köllner, Vanessa\n\n\n"
},
{
"text": "\n142834\nHealth-related quality of life in pediatric patients after allogeneic SCT: development of the PedsQL Stem Cell Transplant module and results of a pilot study.\n\nLawitschka, A\n\nGüclü, ED\n\nVarni, JW\n\nPutz, M\n\nWolff, D\n\nPavletic, S\n\nGreinix, H\n\nPeters, C\n\nFelder-Puig, R\n\nBeiträge in Fachzeitschriften\nISI:000341283000017\n24820217.0\n10.1038/bmt.2014.96\nNone\nWith increased survival after pediatric allogeneic hematopoietic SCT health-related quality of life (HRQL) has emerged as an essential health outcome. The impact of transplant and chronic GVHD (cGVHD)-associated morbidity remains a major obstacle. In 2005, the National Institutes of Health (NIH) Consensus Conference on Criteria for Clinical Trials in cGVHD recommended HRQL tools as an independent measure of the impact of disease burden. The NIH recommendations did not provide a cGVHD-specific tool for HRQOL measures in children. This report focuses on the development of an SCT-specific instrument to assess HRQL in children and adolescents. For the assessment of generic HRQL we chose the PedsQL (Pediatric Quality of Life Inventory) Generic Cores Scales, which have been used in a large number of healthy, acutely ill and chronically ill children and adolescents. To capture SCT- and, specifically, cGVHD-related problems, we developed the PedsQL Stem Cell Transplant module by reviewing the literature, taking over some items/scales of other PedsQL modules, interviewing patients, parents and members of the health-care team, and applying the PedsQL measurement methods. The final PedsQL Stem Cell Transplant module consists of the HRQL domains: pain and hurt, fatigue/sleeping problems/weakness, nausea, worry/anxiety about disease/treatment, nutritional problems, neurocognitive problems, communication about disease/treatment, loneliness, physical functioning and additional somatic complaints (pruritus, skin inflammation, oral problems, eyes or breathing) including patients' and parents' assessment. It was tested in 35 pediatric patients, who were referred to our SCT Outpatient Clinic about 100 days post SCT. Both the generic PedsQL and the SCT-specific scales showed high internal consistency, with Cronbach alpha levels of ⩾0.70 in almost all scales. Most problems were detected within the HRQL domains of physical functioning and pain. The summary scores of the generic PedsQL and the PedsQL Stem Cell Transplant module showed high correlations (r=0.89 in patients' and r=0.81 in parents' assessments). Moreover, both tools discriminated between patients with and without cGVHD. The PedsQL Stem Cell Transplant module is practical for use and suitable across a broad age range (2-18 years) both in patients with and without cGVHD. However, it is still a pilot instrument and needs further development and testing in a larger patient population.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n187875\nGenome-wide association study of circulating interleukin 6 levels identifies novel loci\n\nAhluwalia, TS\n\nPrins, BP\n\nAbdollahi, M\n\nArmstrong, NJ\n\nAslibekyan, S\n\nBain, L\n\nJefferis, B\n\nBaumert, J\n\nBeekman, M\n\nBen-Shlomo, Y\n\nBis, JC\n\nMitchell, BD\n\nde Geus, E\n\nDelgado, GE\n\nMarek, D\n\nEriksson, J\n\nKajantie, E\n\nKanoni, S\n\nKemp, JP\n\nLu, C\n\nMarioni, RE\n\nMcLachlan, S\n\nMilaneschi, Y\n\nNolte, IM\n\nPetrelis, AM\n\nPorcu, E\n\nSabater-Lleal, M\n\nNaderi, E\n\nSeppala, I\n\nShah, T\n\nSinghal, G\n\nStandl, M\n\nTeumer, A\n\nThalamuthu, A\n\nThiering, E\n\nTrompet, S\n\nBallantyne, CM\n\nBenjamin, EJ\n\nCasas, JP\n\nToben, C\n\nDedoussis, G\n\nDeelen, J\n\nDurda, P\n\nEngmann, J\n\nFeitosa, MF\n\nGrallert, H\n\nHammarstedt, A\n\nHarris, SE\n\nHomuth, G\n\nHottenga, JJ\n\nJalkanen, S\n\nJamshidi, Y\n\nJawahar, MC\n\nJess, T\n\nKivimaki, M\n\nKleber, ME\n\nLahti, J\n\nLiu, Y\n\nMarques-Vidal, P\n\nMellstrom, D\n\nMooijaart, SP\n\nMuller-Nurasyid, M\n\nPenninx, B\n\nRevez, JA\n\nRossing, P\n\nRaikkonen, K\n\nSattar, N\n\nScharnagl, H\n\nSennblad, B\n\nSilveira, A\n\nSt Pourcain, B\n\nTimpson, NJ\n\nTrollor, J\n\nvan Dongen, J\n\nVan Heemst, D\n\nVisvikis-Siest, S\n\nVollenweider, P\n\nVolker, U\n\nWaldenberger, M\n\nWillemsen, G\n\nZabaneh, D\n\nMorris, RW\n\nArnett, DK\n\nBaune, BT\n\nBoomsma, DI\n\nChang, YPC\n\nDeary, IJ\n\nDeloukas, P\n\nEriksson, JG\n\nEvans, DM\n\nFerreira, MA\n\nGaunt, T\n\nGudnason, V\n\nHamsten, A\n\nHeinrich, J\n\nHingorani, A\n\nHumphries, SE\n\nJukema, JW\n\nKoenig, W\n\nKumari, M\n\nKutalik, Z\n\nLawlor, DA\n\nLehtimaki, T\n\nMarz, W\n\nMather, KA\n\nNaitza, S\n\nNauck, M\n\nOhlsson, C\n\nPrice, JF\n\nRaitakari, O\n\nRice, K\n\nSachdev, PS\n\nSlagboom, E\n\nSorensen, TIA\n\nSpector, T\n\nStacey, D\n\nStathopoulou, MG\n\nTanaka, T\n\nWannamethee, SG\n\nWhincup, P\n\nRotter, JI\n\nDehghan, A\n\nBoerwinkle, E\n\nPsaty, BM\n\nSnieder, H\n\nAlizadeh, BZ\n\nBeiträge in Fachzeitschriften\nISI:000654638100007\n33517400.0\n10.1093/hmg/ddab023\nNone\nInterleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.\n\nMärz, Winfried\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n9248\nTopical versus systemic capsaicin desensitization: specific and unspecific effects as indicated by modification or reflex micturition in rats.\n\nMaggi, CA\n\nLippe, IT\n\nGiuliani, S\n\nAbelli, L\n\nSomma, V\n\nGeppetti, P\n\nJancsó, G\n\nSanticioli, P\n\nMeli, A\n\nBeiträge in Fachzeitschriften\nISI:A1989AY13800016\n2480553.0\n10.1016/0306-4522(89)90438-7\nNone\nThe aim of this study was to determine the acute and delayed effect of topical application of high concentrations of capsaicin on the rat urinary bladder on micturition reflex and compare the effects of "topical" bladder desensitization with those produced by systemic (subcutaneous administration) capsaicin desensitization. On acute application, capsaicin (1-3%) produced a transient bladder contraction, not observed in capsaicin-pretreated rats. After a transient increase in excitability of the micturition reflex, topical capsaicin suppressed micturition and overflow incontinence ensued which was reverted by intravenous injection of 4-aminopyridine. Topical capsaicin also abolished reflex micturition in rats which had been systemically treated with capsaicin as adults (50 mg/kg, 7 days before) and reduced significantly the neurogenic bladder contractions produced by intravenous dimethylphenylpiperazinium or neurokinin A, while the direct (myogenic) response to neurokinin A was unaffected. In rats whose bladder was pre-exposed to 1-3% topical capsaicin (7 days before) the micturition reflex was affected in a manner which is qualitatively and quantitatively similar to that observed in rats treated with capsaicin as adults, e.g. increase in bladder capacity with no change in voiding efficiency. Topical capsaicin desensitization of the rat urinary bladder was shown to produce a selective impairment of bladder sensory nerves without any sign of desensitization in other areas of the body using both functional (hot plate, wiping, plasma extravasation) and neurochemical (determination of substance P-like immunoreactivity) assays. Systemically administered capsaicin (7 days before) had little effect on reflex micturition at 12.5 mg/kg but the change in bladder capacity produced at a dose of 25 mg/kg was comparable with that produced at 350 mg/kg. These findings provide evidence that selective desensitization of peripheral terminals of capsaicin-sensitive nerves of the rat urinary bladder inactivates their sensory and "efferent" function in a manner similar to that observed after systemic capsaicin desensitization in adult rats. The functional deficit of reflex micturition produced in this way can be overcome by increasing the stimulus to void. By contrast, neonatal capsaicin desensitization produced a long lasting abolition of reflex micturition. These data are in keeping with the hypothesis that adult versus neonatal capsaicin desensitization may be used as a tool to distinguish between two sets of sensory nerves in the rat urinary bladder.(ABSTRACT TRUNCATED AT 400 WORDS)\n\nLippe, Irmgard\n\n\n"
},
{
"text": "\n62680\nRegional distribution of predisposition to maligant hyperthermia in Germany: tate in 1997\n\nHartung, E\n\nAnetseder, M\n\nOlthoff, D\n\nDeutrich, C\n\nLehmann-Horn, F\n\nBaur, C\n\nMortier, W\n\nTzanova, I\n\nDoetsch, S\n\nQuasthoff, S\n\nHofmann, M\n\nSchwefler, B\n\nJantzen, JP\n\nWappler, F\n\nScholz, J\n\nBeiträge in Fachzeitschriften\nISI:000073687700004\n9617422.0\n10.1055/s-2007-994238\nNone\nMalignant hyperthermia (MH) is a rare autosomally dominantly hereditary and potentially life-threatening disease. The prevalence of the genetic MH predisposition is estimated as 1:10, 00 to 1:20, 00. In Germany no data on the regional distribution are available. Therefore, the purpose of this investigation is to summarise and present the epidemiological data of all German MH laboratories. Nine German hospitals offer the specific in vitro contracture test to diagnose the MH predisposition. All German MH laboratories carry out the examination in accordance with the standardised protocol of the European Malignant Hyperthermia Group. The laboratories were asked to provide the number of all patients investigated, excluding those suffering from other neuromuscular diseases, separated according to diagnostic groups and their places of residence, the number of the identified MH-families as well as the number of the clinically suspected and investigated MH cases with their places of residence. Eight MH laboratories provided the requested data. Until September 1997 a total of 2620 patients were investigated. In 865 patients (34%) MH suspicion was confirmed (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH-suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients 757 were clinically suspected MH cases. 35% of these suspected MH cases were classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients places of residence classified as MHS and MHE into a map of Germany demonstrates an exhaustive distribution with an increased regional prevalence in the areas of the MH laboratories. This concentration in the area of the MH laboratories becomes even more evident, when the places of residence of the MH suspected cases are demonstrated. In conclusion, the distribution of the MH predisposition is uniform and exhaustive in Germany. The presented regional concentration of clinically suspected MH cases among the MH laboratories is mainly interpreted as an expression of effective regional education and information. Considering the overall incidence of the MH predisposition as described above only 15-20% of the MH patients have so far been identified. The MH laboratories have already released about 10, 00 patients from the suspicion of MH predisposition. A preliminary prevalence of at least 1:60, 00 to 1:80, 00 in Germany can be estimated according to the presented data.\n\nQuasthoff, Stefan\n\n\n"
},
{
"text": "\n134995\nSexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs.\n\nLa Torre, A\n\nGiupponi, G\n\nDuffy, DM\n\nPompili, M\n\nGrözinger, M\n\nKapfhammer, HP\n\nConca, A\n\nBeiträge in Fachzeitschriften\nISI:000329861900001\n24222012.0\n10.1055/s-0033-1358683\nNone\nSexual dysfunction is a potential side effect of mood stabilizers and anxiolytic drugs: this article presents a critical review of the current literature. Although many studies have been published on sexual side effects of psychopharmacological treatment, only a minority relate to mood stabilizers and anxiolytic drugs. Most of these studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, many of the studies on sexual dysfunction associated with mood stabilizers and anxiolytic drugs are limited by other methodological flaws. While there is evidence to suggest that mood stabilizers, with some exceptions, negatively affect sexual functioning, there is still insufficient evidence to draw any clear conclusions about the effects of anxiolytic drugs on sexual function. There is some weak evidence to indicate that switching from enzyme-inducing to non-enzyme-inducing anticonvulsant drugs, could be clinically useful. Some researchers recommend that sexual dysfunction in patients taking antiepileptic drugs should in general be treated according to standard guidelines for the management of sexual dysfunction, since reliable data on special populations is not available. However, specific approaches may be useful, but cannot yet be recommended until further validating research has been conducted. We did not find evidence supporting the use of any specific treatment strategy for sexual dysfunction associated with anxiolytic treatment.\n This study was conducted in 2013 using the paper and electronic resources of the library of the Azienda Provinciale per i Servizi Sanitari (APSS) in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http://atoz.ebsco.com/Titles/2793, or at the APSS web site (http://www.apss.tn.it). In completing this review, a literature search was conducted using the key words "anxiolytic drugs", "mood stabilizers", "benzodiazepines", "psychotrophic drugs", "sexual dysfunction", "sexual side effects", "treatment-emergent sexual dysfunction". All resulting listed articles were reviewed.\n This review includes studies that investigated the relationship between mood stabilizer and anxiolytic drug treatment and sexual dysfunction. The purpose was to identify possible intervention strategies for sexual dysfunction related to these drugs.\n © Georg Thieme Verlag KG Stuttgart · New York.\n\nKapfhammer, Hans-Peter\n\n\n"
},
{
"text": "\n153963\nEstimating Retinal Blood Flow Velocities by Optical Coherence Tomography.\n\nSeidel, G\n\nAschinger, G\n\nSinger, C\n\nHerzog, SA\n\nWeger, M\n\nHaas, A\n\nWerkmeister, RM\n\nSchmetterer, L\n\nGarhöfer, G\n\nBeiträge in Fachzeitschriften\nISI:000386486900011\n27490674.0\n10.1001/jamaophthalmol.2016.2507\nNone\nWhile optical coherence tomography (OCT) angiography has been considered to evaluate retinal capillary blood flow instead of fluorescein angiography, the reflectance pattern of blood vessels on structural OCT might also provide retinal capillary flow data in the absence of fluorescein angiography. This potential has been insufficiently explored, despite promising data concerning a possible relationship between the reflectance pattern of blood vessels and their perfusion velocity in a laboratory setting.\n To evaluate the potential of retinal blood flow velocity estimation by structural OCT.\n Cross-sectional observational study conducted from June to November 2015 at a tertiary clinical referral center. Sixty arteries (the superior and inferior temporal arteries) from 30 eyes of 30 patients (17 female, 13 male) were included in the study.\n Based on the intraluminal contrast patterns of retinal arteries on OCT, 3 independent graders categorized the blood flow velocities as low, medium, or high. These results and the results from a software-based intraluminal contrast analysis were compared with the retinal blood flow velocities measured by video fluorescein angiography.\n Among the 30 eyes of 30 patients (mean [SD] age, 72.6 [12.3] years; 17 female, 13 male), 15 were controls without retinal occlusion, 6 had a branch retinal artery occlusion, and 9 had a central retinal artery occlusion. When discriminating between low flow velocities and medium or high flow velocities, the graders' sensitivity ranged from 88.2% to 100% (grader 1: 88.2%; 95% CI, 63.6%-98.5%; grader 2: 88.2%; 95% CI, 63.6%-98.5%; and grader 3: 100%; 95% CI, 69.8%-100%) and their specificity ranged from 97.6% to 100% (grader 1: 100%; 95% CI, 87.7%-100%; grader 2: 97.6%; 95% CI, 87.4%-99.9%; and grader 3: 100%; 95% CI, 87.7%-100%). The κ coefficients of the comparison between the 3 graders and the angiography were 0.77 (95% CI, 0.60-0.93; P < .001), 0.64 (95% CI, 0.44-0.83; P < .001), and 0.87 (95% CI, 0.74-0.99; P < .001). In the computer-based assessment, the contrast reduction of the intraluminal pattern could be numerically expressed in a specific coefficient in the model (I2, describing the angular change of the backscattering intensity in the model), which presented nonoverlapping intervals between low flow velocities and medium or high flow velocities (mean [SD] I2, 0.3 [5.3], 20.4 [6.4], and 21.7 [4.0], respectively).\n This study suggests that a low retinal blood flow velocity reflects in a visually distinct contrast reduction of the intraluminal pattern of retinal vessels on OCT. Larger studies are required to assess the clinical benefits.\n\nHaas, Anton\n\nHerzog, Sereina Annik\n\nSeidel, Gerald\n\nSinger, Christoph\n\nWeger, Martin\n\n\n"
},
{
"text": "\n166748\nLong-term effect of critical illness after severe paediatric burn injury on cardiac function in adolescent survivors: an observational study.\n\nHundeshagen, G\n\nHerndon, DN\n\nClayton, RP\n\nWurzer, P\n\nMcQuitty, A\n\nJennings, K\n\nBranski, L\n\nCollins, VN\n\nMarques, NR\n\nFinnerty, CC\n\nSuman, OE\n\nKinsky, MP\n\nBeiträge in Fachzeitschriften\nISI:000453160200018\n29581998.0\n10.1016/S2352-4642(17)30122-0\nPMC5865217\nSepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury.\n Subjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e'), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis.\n Sixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e' (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction.\n Severe pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality.\n Conflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).\n\nBranski, Ludwik\n\nWurzer, Paul\n\n\n"
},
{
"text": "\n178207\nEffect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: a study protocol of a multicentre, placebo-controlled double-blind phase III RCT (the VITDALIZE study).\n\nAmrein, K\n\nParekh, D\n\nWestphal, S\n\nPreiser, JC\n\nBerghold, A\n\nRiedl, R\n\nEller, P\n\nSchellongowski, P\n\nThickett, D\n\nMeybohm, P\n\nVITDALIZE Collaboration Group\n\nBeiträge in Fachzeitschriften\nISI:000512774800179\n31722941.0\n10.1136/bmjopen-2019-031083\nPMC6858186\nObservational studies have demonstrated an association between vitamin D deficiency and increased risk of morbidity and mortality in critically ill patients. Cohort studies and pilot trials have suggested promising beneficial effects of vitamin D replacement in the critical ill, at least in patients with severe vitamin D deficiency. As vitamin D is a simple, low-cost and safe intervention, it has potential to improve survival in critically ill patients.\n In this randomised, placebo-controlled, double-blind, multicentre, international trial, 2400 adult patients with severe vitamin D deficiency (25-hydroxyvitamin D≤12 ng/mL) will be randomised in a 1:1 ratio by www.randomizer.at to receive a loading dose of 540 000 IU cholecalciferol within 72 hours after intensive care unit (ICU) admission, followed by 4000 IU daily for 90 days or placebo. Hypercalcaemia may occur as a side effect, but is monitored by regular checks of the calcium level. The primary outcome is all-cause mortality at 28 days after randomisation. Secondary outcomes are: ICU, hospital, 90-day and 1-year mortality; hospital and ICU length of stay, change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment (SOFA) score, number of organ failures; hospital and ICU readmission until day 90; discharge destination, self-reported infections requiring antibiotics until day 90 and health-related quality of life. Recruitment status is ongoing.\n National ethical approval was obtained by the Ethics Committee of the University of Graz for Austria, Erasme University Brussels (Belgium) and University Hospital Frankfurt (Germany), and will further be gained according to individual national processes. On completion, results will be published in a peer-reviewed scientific journal. The study findings will be presented at national and international meetings with abstracts online.\n NCT03188796, EudraCT-No: 2016-002460-13.\n © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nAmrein, Karin\n\nBerghold, Andrea\n\nDeininger, Marlene Sandra\n\nEller, Philipp\n\nHoffmann, Magdalena\n\nKöstenberger, Markus\n\nLindenau, Ines\n\nMünch, Andreas\n\nPichler, Alexander\n\nRiedl, Regina\n\nSimonis, Holger\n\nUrbanic Purkart, Tadeja\n\nVerheyen, Nicolas Dominik\n\nvon Lewinski, Dirk\n\nZajic, Paul\n\n\n"
},
{
"text": "\n60542\nTransdermal buprenorphine for treatment of chronic tumor and non-tumor pain\n\nLikar, R\n\nGriessinger, N\n\nSadjak, A\n\nSittl, R\n\nBeiträge in Fachzeitschriften\nNone\n12924108.0\nNone\nNone\nPatients with moderate to severe pain were treated with buprenorphine patches in one of 3 concentrations: 35 micrograms/h, 52.5 micrograms/h and 70 micrograms/h (= 0.8 mg/d, 1.2 mg/d and 1.6 mg/d respectively). The aim of this review was to assess the efficacy and tolerability of this transdermal system (TDS) in patients with chronic pain. A total of 445 patients were included in 3 double-blinded studies. The dosage titration with buprenorphine patches followed pretreatment with buprenorphine sublingual tablets, higher doses of weak opioids (level 2 substances), low dose morphine (level 3) or other analgesics. Patients with chronic tumour or non-tumour pain were recruited for these studies and treated with buprenorphine patches or placebo for 6 to 15 days. All patients were offered, in addition, buprenorphine sublingual tablets to be taken as required for supplementary pain relief. Pain intensity, analgesia, consumption of buprenorphine sublingual tablets and sleep duration were all assessed. All patients in the double-blinded studies were between the ages of 22 and 88. 249 patients suffered from tumour pain and 196 patients suffered from non-tumour pain. To examine long-term efficacy and tolerability of the transdermal system, treatment was expanded, if the patients were interested in participating in an open-label-study. In all 3 studies, the number of patients with moderate, severe and very severe pain increased in the placebo-patch treated group, while the patients in the buprenorphine transdermal system treated group had a greater incidence of mild or no pain. A further benefit in the buprenorphine transdermal system treated group was evidenced by a great number of patients with a daily sleep duration of more than 6 hours compared to the placebo group--an indicator of greater well-being. The systemic side-effects were typically opioid in nature and rare and usually only mild. Of particular note was the very low incidence of constipation in only 5.3% of cases. Dermatological reactions to the patches were only rarely encountered. The dermatological reactions consisted mainly of erythema and pruritus with a mild to moderate extent. Half the cases of erythema and more than on third of the cases of pruritus were spontaneously reversible. More than half the patients (53.7%) in the double blind studies wished to continued treatment with buprenorphine transdermal system. These results demonstrate that buprenorphine patches achieved a very good analgesic effect in all 3 studies and that in particular with respect to the quality of life of the patient these patches offer an exceptional alternative to other conventional therapies.\n\nSadjak, Anton\n\n\n"
},
{
"text": "\n124341\nApixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial.\n\nDiener, HC\n\nEikelboom, J\n\nConnolly, SJ\n\nJoyner, CD\n\nHart, RG\n\nLip, GY\n\nO Donnell, M\n\nHohnloser, SH\n\nHankey, GJ\n\nShestakovska, O\n\nYusuf, S\n\nAVERROES Steering Committee and Investigators\n\nBeiträge in Fachzeitschriften\nISI:000301014900010\n22305462.0\n10.1016/S1474-4422(12)70017-0\nNone\nBackground In the AVERROES study, apixaban, a novel factor Xa inhibitor, reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy. We aimed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack (TIA) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events. Methods In AVERROES, 5599 patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin (81-324 mg per day). The mean follow-up was 1.1 years. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Patients and investigators were masked to study treatment. In this prespecified subgroup analysis, we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA. AVERROES is registered at ClinicalTrials.gov, number NCT00496769. Findings In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2.39% per year) compared with 33 in the aspirin group (n=374, 9.16% per year; hazard ratio [HR) (1.29, 95% CI 0.15-0.60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1"68% per year) compared with 80 in the aspirin group (n=2415, 3.06% per year; HR 0.51, 95% CI 0.35-0.74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0.17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2.88, 95% CI 1.77-4.55) but risk of this event did not differ between treatment groups. Interpretation In patients with atrial fibrillation, apixaban is similarly effective whether or not patients have had a previous stroke or TIA. Given that those with previous stroke or TIA have a higher risk of stroke, the absolute benefits might be greater in these patients.\n\n\n"
},
{
"text": "\n145423\nA multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival.\n\nUgurel, S\n\nLoquai, C\n\nKähler, K\n\nHassel, J\n\nBerking, C\n\nZimmer, L\n\nHaubitz, I\n\nSatzger, I\n\nMüller-Brenne, T\n\nMikhaimer, NC\n\nBecker, JC\n\nKilian, KJ\n\nSchadendorf, D\n\nHeinzerling, L\n\nKaatz, M\n\nUtikal, J\n\nGöppner, D\n\nPföhler, C\n\nPflugfelder, A\n\nMössner, R\n\nGutzmer, R\n\nDermatologic Cooperative Oncology Group (DeCOG)\n\nBeiträge in Fachzeitschriften\nISI:000352228700019\n25524477.0\n10.1093/annonc/mdu573\nNone\nKinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib.\n This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib.\n A total of 300 patients from 14 centers were included into this study with a median follow-up time of 13.0 months. Median progression-free survival (PFS) was 5.1 months; median overall survival (OS) was 7.6 months. Best response under vemurafenib was associated with serum lactate dehydrogenase (LDH; ≤ versus >upper normal limit; P = 0.0000001), Eastern Cooperative Oncology Group (ECOG) overall performance status (OPS) (0 versus ≥ 1; P = 0.00089), and BRAF mutation subtype (V600E versus V600K; P = 0.016). Multivariate analysis identified ECOG OPS ≥ 1 [hazard ratio (HR) = 1.88; P = 0.00005], immunotherapy pretreatment (HR = 0.53; P = 0.0067), elevated serum LDH (HR = 1.45; P = 0.012), age >55 years (HR = 0.72; P = 0.019), and chemotherapy pretreatment (HR = 1.39; P = 0.036) as independent predictors of PFS. For OS, elevated serum LDH (HR = 1.99; P = 0.00012), ECOG OPS ≥ 1 (HR = 1.90; P = 0.00063), age >55 years (HR = 0.65; P = 0.011), kinase inhibitor pretreatment (HR = 1.86; P = 0.014), immunotherapy pretreatment (HR = 0.57; P = 0.025), chemotherapy pretreatment (HR = 2.17; P = 0.039), and male gender (HR = 0.70; 95% confidence interval 0.50-0.98; P = 0.039) were found as predictors.\n Our data demonstrate that the type of pretreatment strongly influences the outcome of vemurafenib therapy, with a precedent immunotherapy showing a positive, and a prior chemotherapy and kinase inhibitors showing a negative impact on survival, respectively. Moreover, we show that the patient's OPS, serum LDH, age, and gender independently impact vemurafenib therapy outcome. These findings should be taken into account for the future design of therapy sequencing in BRAF V600 mutation-positive melanoma patients.\n © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.\n\n\n"
}
]
}