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"text": "\n187072\nTrends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic.\n\nGrassner, L\n\nPetr, O\n\nWarner, FM\n\nDedeciusova, M\n\nMathis, AM\n\nPinggera, D\n\nGsellmann, S\n\nMeiners, LC\n\nFreigang, S\n\nMokry, M\n\nResch, A\n\nKretschmer, T\n\nRossmann, T\n\nNavarro, FR\n\nGruber, A\n\nSpendel, M\n\nWinkler, PA\n\nMarhold, F\n\nSherif, C\n\nWais, JP\n\nRössler, K\n\nPfisterer, W\n\nMühlbauer, M\n\nTrivik-Barrientos, FA\n\nRath, S\n\nVoldrich, R\n\nKrska, L\n\nLipina, R\n\nKerekanic, M\n\nFiedler, J\n\nKasik, P\n\nPriban, V\n\nTichy, M\n\nKrupa, P\n\nCesak, T\n\nKroupa, R\n\nCallo, A\n\nHaninec, P\n\nPohlodek, D\n\nKrahulik, D\n\nSejkorova, A\n\nSames, M\n\nDvorak, J\n\nSuchomel, P\n\nTomas, R\n\nKlener, J\n\nJuran, V\n\nSmrcka, M\n\nLinzer, P\n\nKaiser, M\n\nHrabovsky, D\n\nJancalek, R\n\nKälin, V\n\nBozinov, O\n\nNiggli, C\n\nSerra, C\n\nGuatta, R\n\nKuhlen, DE\n\nWanderer, S\n\nMarbacher, S\n\nLavé, A\n\nSchaller, K\n\nEsculier, C\n\nRaabe, A\n\nKramer, JLK\n\nThomé, C\n\nNetuka, D\n\nBeiträge in Fachzeitschriften\nISI:000630511700015\n33731753.0\n10.1038/s41598-021-85526-6\nPMC7969942\nThe world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th-April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4, 52 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017-2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.\n\nFreigang, Sascha\n\nMokry, Michael\n\n\n"
},
{
"text": "\n6842\nThe use of atorvastatin treatment in usual care environments: pooled analysis of six prospective, observational studies in 90,535 patients.\n\nVetter, S\n\nRuf, G\n\nRegourd, E\n\nMärz, W\n\nBeiträge in Fachzeitschriften\nISI:000223030000002\n15366322.0\nNone\nNone\nOBJECTIVE: We investigated the pattern of use as well as the efficacy and safety of atorvastatin in unselected inpatients and outpatients in routine clinical practice in Germany. DESIGN: Six prospective, observational studies with a similar design were pooled. The studies lasted for up to 12 weeks and data from 90, 35 patients (7, 87 inpatients, 83, 48 outpatients) were collected. The studies were performed in Germany in 2000 and 2001. Hospital or office-based physicians selected hyperlipemic patients with or without coronary heart disease (CHD) for once daily treatment with atorvastatin. Information on demographics, atorvastatin dosage, concomitant medication, concomitant diseases, cardiovascular risk factors, lipid profile as well as adverse events (AEs) and serious adverse events (SAEs) were obtained at 2-3 visits and descriptively analyzed. MAIN OUTCOME MEASURES: Absolute and relative changes in lipid parameters, percentage of patients with low-density lipoprotein cholesterol (LDL-C) values within target ranges according to the National Cholesterol Education Program (NCEP) criteria, and frequencies of AEs. RESULTS: On average, patients were treated for 22.4 days (inpatients) and 106.0 days (outpatients), respectively. The overall mean atorvastatin dose of 14.4 mg/day was well tolerated by a heterogeneous patient population with a variety of concomitant diseases and medications. Overall, 0.8% of patients suffered from one or more AEs, 0.6% were considered as treatment-related. The corresponding figures for SAEs and treatment-related SAEs were 0.1% (131 patients) and 0.01% (13 patients), respectively. Subgroup analyses did not reveal a particular safety concern in any subgroup. In total, 99% of patients judged the tolerability of atorvastatin as very good or good. The mean percentages of reduction in LDL-C at the final visit ranged between 24.8% and 28.5%. Overall, 26.3% of patients reached the NCEP LDL-C goal compared to 4.9% at baseline. Inpatients achieved the target range for LDL-C more frequently than outpatients (35.3% vs 25.6%). An underuse of atorvastatin titration in clinical practice in Germany was apparent, particularly in outpatients. CONCLUSIONS: The use of atorvastatin in usual care environments is effective and safe. There is a gap between treatment guidelines and clinical practice in Germany as reflected by the number of patients outside the target range for LDL-C. A major opportunity exists to increase the number of patients who achieve LDL-C target ranges by appropriate dose titration and/or giving patients a higher initial dose. Available guidelines need to be implemented more stringently.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n107563\nNo Rectopexy Versus Rectopexy Following Rectal Mobilization for Full-Thickness Rectal Prolapse: A Randomized Controlled Trial.\n\nKaras, JR\n\nUranues, S\n\nAltomare, DF\n\nSokmen, S\n\nKrivokapic, Z\n\nHoch, J\n\nBartha, I\n\nBergamaschi, R\n\nfor the Rectal Prolapse Recurrence Study Group\n\nBeiträge in Fachzeitschriften\nISI:000285377500006\n21160310.0\n10.1007/DCR.0b013e3181fb3de3\nNone\nBACKGROUND: No randomized controlled trial has compared no rectopexy with rectopexy for external full-thickness rectal prolapse. OBJECTIVE: This study was performed to test the hypothesis that recurrence rates following no rectopexy are not inferior to those following rectopexy for fullthickness rectal prolapse. DESIGN: This was a multicenter randomized controlled trial. Eligible patients were randomly assigned to no rectopexy or rectopexy. The end point was recurrence rates defined as the presence of external full-thickness rectal prolapse after surgery. A prerandomized controlled trial meta-analysis suggested a sample size of 251 patients based on a 15% expected difference in the 5-year cumulative recurrence rate. Recurrence-free curves were generated and compared using the Kaplan-Meier method and log-rank test, respectively. Data were presented as median (range). SETTING: This study was conducted in 41 tertiary centers in 21 countries. PATIENTS: Patients with prior surgery for rectal prolapse or pelvic floor descent were not included. INTERVENTIONS: The no-rectopexy arm was defined as abdominal surgery with rectal mobilization only. The rectopexy arm was defined as abdominal surgery with mobilization and rectopexy. Sigmoid resection was not randomized and was added in the presence of constipation. MAIN OUTCOME MEASURES: Two hundred fifty-two patients with external full-thickness rectal prolapse were randomly assigned to undergo no rectopexy or rectopexy in 41 centers. All patients but one underwent the allocated intervention. One hundred sixteen no-rectopexy patients were comparable to 136 rectopexy patients for age (P = .21), body mass index (P = .61), ASA grade (P = .29), and previous abdominal surgery (P = .935), but not for sex (P = .013) and external full-thickness rectal prolapse length (8 (1-25) cm vs 5 (1-20) cm, P = .026). Sigmoid resection was performed more frequently in the no-rectopexy arm (P = .001). There was no significant difference in complication rates (11% vs 17.9%; P = .139). The mortality rate was 0.8%. The loss of patients to 5-year follow-up was 10.3%. Actuarial analysis demonstrated a significant difference in 5-year recurrence rates between study arms (8.6% vs 1.5%) (log-rank, P = .003). LIMITATIONS: Limitations were the high proportion of male patients, randomization timing, the lack of standardization for rectopexy technique, and the 10% loss to follow-up. CONCLUSIONS: Recurrence rates following no rectopexy are inferior to those following rectopexy for external fullthickness rectal prolapse.\n\nUranüs, Selman\n\n\n"
},
{
"text": "\n108660\nDacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG).\n\nHauschild, A\n\nGarbe, C\n\nStolz, W\n\nEllwanger, U\n\nSeiter, S\n\nDummer, R\n\nUgurel, S\n\nSebastian, G\n\nNashan, D\n\nLinse, R\n\nAchtelik, W\n\nMohr, P\n\nKaufmann, R\n\nFey, M\n\nUlrich, J\n\nTilgen, W\n\nBeiträge in Fachzeitschriften\nISI:000168635800005\n11308250.0\n10.1054/bjoc.2001.1731\nPMC2363865\nIn several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.\n\n\n"
},
{
"text": "\n111355\nTherapeutic approaches in the treatment of juvenile dermatomyositis in patients with recent-onset disease and in those experiencing disease flare: An international multicenter PRINTO study.\n\nHasija, R\n\nPistorio, A\n\nRavelli, A\n\nDemirkaya, E\n\nKhubchandani, R\n\nGuseinova, D\n\nMalattia, C\n\nCanhao, H\n\nHarel, L\n\nFoell, D\n\nWouters, C\n\nDe Cunto, C\n\nHuemer, C\n\nKimura, Y\n\nMangge, H\n\nMinetti, C\n\nNordal, EB\n\nPhilippet, P\n\nGarozzo, R\n\nMartini, A\n\nRuperto, N\n\nfor the Paediatric Rheumatology International Trials Organisation (PRINTO)\n\nBeiträge in Fachzeitschriften\nISI:000295293000036\n21647864.0\n10.1002/art.30475\nNone\nObjective. To evaluate response to therapy over a 24-month period in a large prospective international cohort of patients with juvenile dermatomyositis (DM). Methods. The study included 145 patients with recent-onset juvenile DM and 130 juvenile DM patients experiencing disease flare, all of whom were <18 years old. Disease activity parameters and therapeutic approaches in 4 geographic areas were analyzed at baseline and at 6, 12, and 24 months. Response was assessed according to the Pediatric Rheumatology International Trials Organization (PRINTO) juvenile DM response criteria, and data were reported "as observed" and in the intent-to-treat (ITT) population. Results. Patients with recent-onset juvenile DM at baseline had higher baseline disease activity and greater improvement over 24 months when compared to juvenile DM patients experiencing disease flare at baseline. Methotrexate (MTX) or high-dose corticosteroids were administered more frequently to patients with recent-onset juvenile DM, compared to juvenile DM patients experiencing disease flare, who were more likely to receive cyclosporine. Compared to patients from Western and Eastern Europe, a higher proportion of patients from South and Central America and North America received pulse steroids, and the average steroid dosage was higher in the North American and South and Central American patients. The use of MTX was similar in all 4 regions, while cyclosporin A was more frequently used in Western Europe. In the "as observed" analysis, 57.9% of the patients with recent-onset juvenile DM and 36.4% of the patients experiencing disease flare (P<0.001) reached at least a 70% response by PRINTO criteria at 6 months; these proportions had increased at month 24 to 78.4% and 51.2%, respectively (P<0.001). Corresponding results of the ITT analysis were much lower, with only one-third of the patients able to maintain the initial assigned therapy over 24 months. Conclusion. Patients with recent-onset juvenile DM are more likely to achieve significant clinical improvement over 24 months, when compared to patients experiencing flares of juvenile DM. Internationally, various therapeutic approaches are used to treat this disease.\n\nMangge, Harald\n\n\n"
},
{
"text": "\n121206\nPatients with polymorphic light eruption have decreased serum levels of 25-hydroxyvitamin-D(3) that increase upon 311 nm UVB photohardening.\n\nGruber-Wackernagel, A\n\nObermayer-Pietsch, B\n\nByrne, SN\n\nWolf, P\n\nBeiträge in Fachzeitschriften\nISI:000311281900008\n22952008.0\n10.1039/c2pp25188d\nNone\nBackground: Polymorphic light eruption (PLE) is a very common condition whose pathogenesis may involve immunological abnormalities. Vitamin D sufficiency is thought to be important for normal immune function. Objective: To determine whether PLE patients are vitamin D deficient and to study how photohardening with 311 nm UVB affects the vitamin D status of PLE patients. Methods: The vitamin D status of 23 PLE patients (21 females and 2 males; age range, 18-55 years) was analysed at four different time points (early spring, late spring, summer, and winter) by measuring 25-hydroxyvitamin-D-3 (25(OH)D) serum levels through a standardised immunoassay. Fifteen of those patients received 311 nm UVB in early spring for prevention of PLE symptoms. 25(OH)D levels of the PLE patients were compared to that of 23 sex-, age-, and body-mass-index post hoc-matched control subjects. Results: PLE patients had low levels of 25(OH)D throughout the year compared to that of the control subjects. At baseline in early spring, the mean +/- SD 25(OH)D level was 14.9 +/- 3.0 ng ml(-1) in the PLE patients that would later receive 311 nm UVB and 14.4 +/- 2.4 ng ml(-1) in the patients not receiving 311 nm UVB. Successful prophylactic treatment with 311 nm UVB significantly increased 25(OH)D levels to a mean of 21.0 +/- 3.4 ng ml(-1) (p ANDlt; 0.001; ANOVA, TukeyANDapos;s test). Heading into summer, the 25(OH)D levels in treated patients decreased again, reaching their lowest levels in winter. In contrast, the 25(OH)D levels of untreated PLE patients stayed in the low range in early and late spring but increased by trend towards summer, reaching similar levels to that of the PLE patients who had received 311 nm UVB (17.1 +/- 2.3 vs. 17.3 +/- 6.0 ng ml-1). Like the treated PLE patients, 25(OH)D levels of untreated patients significantly decreased in winter to comparable levels (12.2 +/- 1.9 vs. 13.8 +/- 1.8 ng ml(-1)). Taken together, the 25(OH)D levels of PLE patients were significantly lower at all time points than that observed in the matched control population (34.4 +/- 12.5 ng ml(-1)) (p ANDlt; 0.000003). Conclusions: PLE patients have low 25(OH)D serum levels. 311 nm UVB phototherapy that prevented PLE symptoms increased those levels. Thus, we speculate that boosting levels of vitamin D may be important in ameliorating PLE.\n\nGruber-Wackernagel, Alexandra\n\nObermayer-Pietsch, Barbara\n\nWolf, Peter\n\n\n"
},
{
"text": "\n131020\nThe prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis.\n\nRodseth, RN\n\nBiccard, BM\n\nLe Manach, Y\n\nSessler, DI\n\nLurati Buse, GA\n\nThabane, L\n\nSchutt, RC\n\nBolliger, D\n\nCagini, L\n\nCardinale, D\n\nChong, CP\n\nChu, R\n\nCnotliwy, M\n\nDi Somma, S\n\nFahrner, R\n\nLim, WK\n\nMahla, E\n\nManikandan, R\n\nPuma, F\n\nPyun, WB\n\nRadović, M\n\nRajagopalan, S\n\nSuttie, S\n\nVanniyasingam, T\n\nvan Gaal, WJ\n\nWaliszek, M\n\nDevereaux, PJ\n\nBeiträge in Fachzeitschriften\nISI:000329839200012\n24076282.0\n10.1016/j.jacc.2013.08.1630\nNone\nThe objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured.\n Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done.\n We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery.\n Eighteen eligible studies provided individual patient data (n = 2, 79). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1, 80 to 1, 04; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1, 20 to 1, 00; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery.\n Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.\n Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.\n\nMahla, Elisabeth\n\n\n"
},
{
"text": "\n167638\nAssociation of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer.\n\nMargonis, GA\n\nBuettner, S\n\nAndreatos, N\n\nKim, Y\n\nWagner, D\n\nSasaki, K\n\nBeer, A\n\nSchwarz, C\n\nLøes, IM\n\nSmolle, M\n\nKamphues, C\n\nHe, J\n\nPawlik, TM\n\nKaczirek, K\n\nPoultsides, G\n\nLønning, PE\n\nCameron, JL\n\nBurkhart, RA\n\nGerger, A\n\nAucejo, FN\n\nKreis, ME\n\nWolfgang, CL\n\nWeiss, MJ\n\nBeiträge in Fachzeitschriften\nISI:000439168600001\n29799910.0\n10.1001/jamasurg.2018.0996\nPMC6137519\nBRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied.\n To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations.\n In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes.\n Hepatectomy in patients with CRLM.\n The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS).\n Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).\n The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.\n\nGerger, Armin\n\nSmolle, Maria Anna\n\nWagner, Doris\n\n\n"
},
{
"text": "\n174473\nAddressing Profiles of Systemic Inflammation Across the Different Clinical Phenotypes of Acutely Decompensated Cirrhosis.\n\nTrebicka, J\n\nAmoros, A\n\nPitarch, C\n\nTitos, E\n\nAlcaraz-Quiles, J\n\nSchierwagen, R\n\nDeulofeu, C\n\nFernandez-Gomez, J\n\nPiano, S\n\nCaraceni, P\n\nOettl, K\n\nSola, E\n\nLaleman, W\n\nMcNaughtan, J\n\nMookerjee, RP\n\nCoenraad, MJ\n\nWelzel, T\n\nSteib, C\n\nGarcia, R\n\nGustot, T\n\nRodriguez Gandia, MA\n\nBañares, R\n\nAlbillos, A\n\nZeuzem, S\n\nVargas, V\n\nSaliba, F\n\nNevens, F\n\nAlessandria, C\n\nde Gottardi, A\n\nZoller, H\n\nGinès, P\n\nSauerbruch, T\n\nGerbes, A\n\nStauber, RE\n\nBernardi, M\n\nAngeli, P\n\nPavesi, M\n\nMoreau, R\n\nClària, J\n\nJalan, R\n\nArroyo, V\n\nBeiträge in Fachzeitschriften\nISI:000461592400001\n30941129.0\n10.3389/fimmu.2019.00476\nPMC6434999\nBackground: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5-2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF). Results: Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating "full-blown" systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF (p < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes. Conclusions: Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.\n\nÖttl, Karl\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n175230\nEffective Increase of Serum Vitamin D3 by IV Application of a Cholecalciferol-N-Acetyl-Galactosamine-Stabilized Dimer: a Clinical Murine Trial Study.\n\nGreilberger, J\n\nGreilberger, M\n\nPetek, T\n\nStiegler, P\n\nLeber, B\n\nReichl, H\n\nKamel, A\n\nHerwig, R\n\nBeiträge in Fachzeitschriften\nISI:000468526200023\n31115209.0\n10.7754/Clin.Lab.2019.181114\nNone\nPre-clinical toxicology studies of human Gc-protein (vitamin D binding protein) are of special interest as to the transport of vitamin D and its biological activities. We have demonstrated that the oral application of a special dimeric vitamin D complex reduces oxidative stress and increases the quality of life in autistic children. Therefore, safety and toxic effects of two dimeric cholecalciferol-N-acetyl-galactosamine-albumin complexes were evaluated in increasing intravenous (iv.) vitamin D levels administered in a pre-clinical trial in mice over a 5-week period.\n Over a period of 5 weeks, two times a week, mice received iv. administration of one of the following: (a) 1.2 IE of vitamin D-N-acetyl-galactosamine-albumin (Vitamin D3 NAGA, ImmunoD® group), (b) 1.2 IE of vitamin-D-poly-N-acetyl-galactosamine-albumin (Poly-Nac group), or (c) isotonic saline solution (sham group). Before and after the trial, red and white blood cell panels (RBS, WBC and platelets) were determined. Furthermore, vitamin D levels, electrolytes, and C-reactive protein levels were measured directly before sacrificing.\n No toxic effects were observed during iv. injection with dimeric vitamin D complexes, neither in the sham group, nor in the two treatment groups. Vitamin D levels increased significantly within 5 weeks in the Poly-Nac group (26.6 ± 8.8 ng/mL; p = 0.001) compared to the sham group (3.1 ± 0.9 ng/mL), and the Poly-Nac group to the ImmunoD group (7.0 ± 3.6 ng/mL; p = 0.003). A significant increase of vitamin D was also obtained in favor of the ImmunoD group compared to the sham (p = 0.03). Electrolytes (K, Na, Cl, Mg, Ca) and C-reactive protein showed no significant differences after administration in all three mice groups. Also, no significant differences were observed between these three groups in the WBC and RBC blood panels.\n The two dimeric vitamin D complexes used in this pre-clinical study showed no side or toxic effects after iv. administration in mice, but a sole increase in vitamin D levels without any change in electrolytes or blood cells. Therefore, we assume this newly developed composition to be safe in oral or iv.-administration and further pre-clinical studies can be conducted to evaluate the value in treatment of various diseases related to vitamin D deficiencies.\n\nGreilberger, Joachim\n\nLeber, Bettina\n\nStiegler, Philipp\n\n\n"
},
{
"text": "\n955\nEndoscopy of the lacrimal system.\n\nMüllner, K\n\nBodner, E\n\nMannor, GE\n\nBeiträge in Fachzeitschriften\nISI:000081829300019\n10413700.0\n10.1136/bjo.83.8.949\nPMC1723140\nBACKGROUND/AIM: Until recently, diagnosis of disorders of the lacrimal system has depended on digital dacryocystography and on clinical examinations such as the fluorescein dye test, lacrimal probing, and irrigation. The lacrimal system and its mucous membranes can now be viewed directly with a lacrimal endoscope. While the first endoscopes were rigid and limited by poor picture quality in axial illuminations, the new generation of endoscopes are a great leap forward for new diagnostic and therapeutic approaches. METHODS: 132 patients ranging in age from 8 months to 73 years with nasolacrimal obstruction were referred to the lacrimal department. Diagnostic lacrimal imaging utilising various small calibre endoscopes less than 0.5 mm in external diameter was performed. The endoscopes are coupled to specially designed lacrimal probes as well as a CCD camera and a video recorder. The imaging was performed during standard lacrimal probing and irrigation in an outpatient clinic setting in 120 of 132 patients RESULTS: All patients reported the pain of endoscopy as being similar to that of standard lacrimal probing and irrigation. No adverse effects such as bleeding or lacrimal perforation were noted. Endoscopic manipulation was not too difficult and the picture quality, depth of focus, and illumination were satisfactory in all cases. The most common site of stenosis was the nasolacrimal duct (59 patients), followed by the lacrimal sac (39 patients) and the canaliculi (34 patients). In 25 patients, partial obstruction, rather than complete stenosis, was visualised as a narrow lumen, which widened during irrigation. In 14 of 28 patients, obstruction was due to canalicular submucosal folds and was removed with laser. In addition, the colour and consistency of the lining mucosa correlated with type of obstruction. Normal mucosa is smooth and light pink in colour. Inflammatory changes manifest as thickened and reddish grey mucosa. More complete stenosis is shown as fibrotic plaques with grey white inelastic membranes. CONCLUSION: Lacrimal endoscopy is a new, non-invasive method used to view directly and localise obstructions precisely. It allows differentiation between inflammatory, partial, and complete stenosis. Endoscopy enables one to choose the appropriate surgical therapy for patients. Patients tolerated the procedure well without any adverse reactions or effects. While it may not replace standard probing and irrigation, this technique is an extremely useful adjunct in determining the proper surgical modality, ease, and tolerance of the endoscopic manipulation by patients, and obtaining sharp and clear images of the nasolacrimal outflow system anatomy and pathology. Differentiation of various types of obstruction by precise location and severity can be achieved.\n\n\n"
},
{
"text": "\n135933\nQuantitative electroencephalography: a method to assess cerebral injury after hypothermic circulatory arrest.\n\nMezrow, CK\n\nMidulla, PS\n\nSadeghi, AM\n\nGandsas, A\n\nWang, W\n\nBodian, C\n\nShing, HH\n\nZappulla, R\n\nDapunt, OE\n\nGriepp, RB\n\nBeiträge in Fachzeitschriften\nISI:A1995QX36800015\n7739254.0\n10.1016/S0022-5223(95)70318-7\nNone\nAlthough hypothermic circulatory arrest and low-flow cardiopulmonary bypass are routinely used for surgical correction of congenital cardiac anomalies, use of long durations of arrest, often required for more complex repairs, raises serious concerns about cerebral safety. Searching for an intraoperative assessment that can reliably predict cerebral injury, we have found an excellent correlation between changes in quantitative electroencephalography intraoperatively and immediately postoperatively after prolonged hypothermic arrest, and neurologic and behavioral evidence of cerebral injury. After epidural placement of four recording electroencephalographic electrodes and baseline neurologic/behavioral and electroencephalographic assessment, 32 puppies were randomly assigned to one of four groups: hypothermic controls in which cooling to 18 degrees C was followed immediately by rewarming, 30 minutes of hypothermic circulatory arrest at 18 degrees C, 90 minutes of arrest at 18 degrees C, and 90 minutes of low-flow cardiopulmonary bypass at 25 ml/kg per minute at 18 degrees C. An electroencephalogram was recorded at baseline, after cooling, during rewarming, and at 2, 4, and 8 hours after the start of rewarming, as well as before the operation and 1 week after the operation. Postoperative neurologic and behavioral outcome was assessed 24 hours after cardiopulmonary bypass and daily for 1 week by means of a graded scale in which 0 is normal and 12 and 13 indicate severe neurologic injury (coma and death). Thirty animals survived the experimental protocol: two animals in the 90-minute hypothermic arrest group died before neurologic evaluation could be completed, and the remainder exhibited various degrees of neurologic and behavioral impairment, more severe on day 1 than on day 6. No animal in the remaining groups had a significant neurologic deficit. Quantitative electroencephalographic analysis shows marked differences between the 90-minute arrest group and the controls in the percent electroencephalographic silence during rewarming and at 2 hours, and in the percent recovery of baseline power at 2, 4, and 8 hours. At 2 hours after the start of rewarming, a correlation between electroencephalographic amplitude and neurologic/behavioral score on day 1 was carried out, which predicts with great certainty (p < 0.00001) that if electroencephalographic power at this time is less than 500 microV2, overt neurologic injury will subsequently become apparent. In addition, a significant shift from higher to lower frequency in the day 6 postoperative electroencephalogram compared with baseline occurs only in the 90-minute arrest group.(ABSTRACT TRUNCATED AT 400 WORDS)\n\n\n"
},
{
"text": "\n162585\nMedian time to low disease activity is shorter in tocilizumab combination therapy with csDMARDs as compared to tocilizumab monotherapy in patients with active rheumatoid arthritis and inadequate responses to csDMARDs and/or TNF inhibitors: sub-analysis of the Swiss and Austrian patients from the ACT-SURE study.\n\nMueller, RB\n\nGraninger, W\n\nSidiropoulos, P\n\nGoger, C\n\nvon Kempis, J\n\nBeiträge in Fachzeitschriften\nISI:000410653600005\n28776300.0\n10.1007/s10067-017-3779-2\nNone\nTo analyse efficacy and safety of tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and/or tumour necrosis factor (TNF) inhibitors of the Swiss and Austrian patients from the ACT-SURE study. This is a sub-analysis of RA patients from Switzerland and Austria, who participated in the international phase 3b, open-label, ACT-SURE study. Patients with an inadequate response to csDMARDs or TNF antagonists receiving 8 mg/kg of IV tocilizumab every 4 weeks during a 24-week time period were included into the study. Therapy with one or more csDMARDs could be continued as combination therapy with tocilizumab (Combo) or stopped, resulting in tocilizumab monotherapy (Mono), at the treating physician's discretion. These two patient groups were analysed in separate and compared. Overall, 107 (22 on Mono vs. 85 on Combo) patients were treated with tocilizumab. The percentage of patients with at least one adverse event was significantly lower in the tocilizumab combination (58.8%) as compared to the monotherapy group (81.8%, p = 0.0458). No differences in ACR20/50/70/90 response rates were observed between both treatment groups at week 24 (Mono 63.6, 40.9, 22.7, and 18.2% vs. Combo 61.2, 43.5, 25.9, and 10.6%). The median time to low disease activity (LDA) was significantly shorter in patients treated with tocilizumab combination therapy (Mono 9.1, Combo 7.9 weeks, log rank p = 0.038). In this post hoc regional sub-analysis of the ACT-SURE study, no differences for disease activity were found comparing the two patient groups at week 24. However, median time to LDA was statistically shorter in patients treated with tocilizumab combination therapy as compared to tocilizumab monotherapy. Consequently, adding tocilizumab to csDMARD therapy rather than changing to tocilizumab monotherapy may be, in our opinion, the safest strategy to reach maximum effect in RA patients with active disease despite treatment with csDMARD. csDMARDs can be withdrawn either immediately due to adverse events or after at least low disease activity has been reached.\n\nGraninger, Winfried\n\n\n"
},
{
"text": "\n175418\nTrying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths.\n\nMartucci, G\n\nMcNally, D\n\nParekh, D\n\nZajic, P\n\nTuzzolino, F\n\nArcadipane, A\n\nChristopher, KB\n\nDobnig, H\n\nAmrein, K\n\nBeiträge in Fachzeitschriften\nISI:000470310000001\n31164148.0\n10.1186/s13054-019-2472-z\nPMC6549317\nVitamin D supplementation has shown promise for reducing mortality in the intensive care setting. As a steroid prohormone with pleiotropic effects, there may be a lag between administration and observing clinical benefit. This secondary analysis of the VITdAL-ICU study sought to explore whether the effect size of vitamin D on mortality was different when study participants who died or were discharged early were excluded.\n The VITdAL-ICU study was a randomized, placebo-controlled trial in critically ill adults who received placebo or 540, 00 IU cholecalciferol followed by monthly supplementation. The effect of vitamin D on 28-day mortality was evaluated after exclusion of participants who died or were discharged within 7 days from study drug administration, according to vitamin D concentrations on day 3, using a bivariate analysis adjusted for confounders and in a stepwise multiple analysis.\n Of 475 study participants, 65 died or were discharged within the first 7 days. In the remaining 410 patients, vitamin D supplementation was associated with a reduction in 28-day mortality [OR 0.58 (95% CI 0.35-0.97) p value = 0.035]. The effect on mortality was not significant after adjusting for age, severity scores, female gender, chronic liver and kidney disease, COPD, diagnosis of the tumor, mechanical ventilation, and vasopressors at enrollment (all p > 0.05). In a multiple model, the mortality reduction by vitamin D supplementation did not remain independently significant [OR 0.61 (95% CI 0.35-1.05) p = 0.075]. Vitamin D metabolite response, in the treatment group, demonstrated that survivors at 28 days, had higher levels of 25-hydroxyvitamin D (34.4 vs 25.4 ng/ml, p = 0.010) and 1, 5-dihydroxyvitamin D (107.6 vs 70.3 pg/ml, p = 0.049) on day 3. The increase of plasma metabolites after vitamin D oral supplementation, independent of the baseline value, was associated with lower odds of death [OR 0.48 (95% CI 0.27-0.87) p value = 0.016].\n High-dose vitamin D3 supplementation was associated with a reduction of 28-day mortality in a mixed population of critically ill adults with vitamin D deficiency when excluding patients who died or were discharged within 7 days after study inclusion. However, this survival benefit was not independently confirmed when adjusted for other factors strongly associated with mortality.\n\nAmrein, Karin\n\nZajic, Paul\n\n\n"
},
{
"text": "\n176360\nGeneration of a cohort of whole-torso cardiac models for assessing the utility of a novel computed shock vector efficiency metric for ICD optimisation.\n\nPlancke, AM\n\nConnolly, A\n\nGemmell, PM\n\nNeic, A\n\nMcSpadden, LC\n\nWhitaker, J\n\nO'Neill, M\n\nRinaldi, CA\n\nRajani, R\n\nNiederer, SA\n\nPlank, G\n\nBishop, MJ\n\nBeiträge in Fachzeitschriften\nISI:000487566700007\n31352217.0\n10.1016/j.compbiomed.2019.103368\nPMC6873640\nImplanted cardiac defibrillators (ICDs) seek to automatically detect and terminate potentially lethal ventricular arrhythmias by applying strong internal electric shocks across the heart. However, the optimisation of the specific electrode design and configurations represents an intensive area of research in the pursuit of reduced shock strengths and fewer device complications and risks. Computational whole-torso simulations play an important role in this endeavour, although knowing which specific metric should be used to assess configuration efficacy and assessing the impact of different patient anatomies and pathologies, and the corresponding effect this may have on different metrics has not been investigated. We constructed a cohort of CT-derived high-resolution whole torso-cardiac computational models, including variants of cardiomyopathies and patients with differing torso dimensions. Simulations of electric shock application between electrode configurations corresponding to transveneous (TV-ICD) and subcutaneous (S-ICD) ICDs were modelled and conventional metrics such as defibrillation threshold (DFT) and impedance computed. In addition, we computed a novel metric termed the shock vector efficiency (η), which quantifies the fraction of electrical energy dissipated in the heart relative to the rest of the torso. Across the cohort, S-ICD configurations showed higher DFTs and impedances than TV-ICDs, as expected, although little consistent difference was seen between healthy and cardiomyopathy variants. η was consistently <2% for S-ICD configurations, becoming as high as 13% for TV-ICD setups. Simulations also suggested that a total torso height of approximately 20 cm is required for convergence in η. Overall, η was seen to be approximately negatively correlated with both DFT and impedance. However, important scenarios were identified in which certain values of DFT (or impedance) were associated with a range of η values, and vice-versa, highlighting the heterogeneity introduced by the different torsos and pathologies modelled. In conclusion, the shock vector efficiency represents a useful additional metric to be considered alongside DFT and impedance in the optimisation of ICD electrode configurations, particularly in the context of differing torso anatomies and cardiac pathologies, which can induce significant heterogeneity in conventional metrics of ICD efficacy.\n Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nNeic, Aurel-Vasile\n\nPlank, Gernot\n\n\n"
},
{
"text": "\n183063\nDifferences in Hypothalamic Lipid Profiles of Young and Aged Male Rats With Impaired and Unimpaired Spatial Cognitive Abilities and Memory.\n\nWackerlig, J\n\nKöfeler, HC\n\nKorz, V\n\nHussein, AM\n\nFeyissa, DD\n\nHöger, H\n\nUrban, E\n\nLanger, T\n\nLubec, G\n\nLubec, J\n\nBeiträge in Fachzeitschriften\nISI:000552343800001\n32719597.0\n10.3389/fnagi.2020.00204\nPMC7349000\nLipids play a major role for several brain functions, including cognition and memory. There is a series of work on individual lipids showing involvement in memory mechanisms, a concise lipidome was not reported so far. Moreover, there is no evidence for age-related memory decline and there is only work on brain of young vs. aging animals. Aging animals, however, are not a homogeneous group with respect to memory impairments, thus animals with impaired and unimpaired memory can be discriminated. Following recent studies of hippocampal lipid profiles and hypothalamus controlled hormone profiles, the aim of this study was to compare hypothalamic, lipidomic changes in male Sprague-Dawley rats between young (YM), old impaired (OMI) and old unimpaired (OMU) males. Grouping criterions for aged rats were evaluated by testing them in a spatial memory task, the hole-board. YMs were also tested. Subsequently brains were removed, dissected and hypothalami were kept at -80°C until sample preparation and analysis on liquid chromatography / mass spectrometry (LC-MS). Significant differences in the amounts of a series of lipids from several classes could be detected between young and aged and between OMI and OMU. A large number of lipids were increased in OMI and a smaller number in OMU as compared to young rats. Differences of lipid ratios (log2 of ratio) between OMI and OMU consisted of glycerophosphocholines (aPC 36:2 and 36:3; PC 34:0, 36:1, 36:3 and 40:2); Glycerophosphoethanolamines (aPE 34:2, 38:5 and 40:5; LPE 18:1, 20:1, 20:4, 22:4 and 22:6; PE36:1 and 38:4); glycerophosphoserines (PS 36:1, 40:4, and 40:6); triacylglycerol TG 52:4; ceramide Cer 17:2 and sphingomyelin SM 20:0. Thus, hypothalamic lipid profiles across different lipid classes discriminate aged male animals into OMU and OMI. The underlying mechanisms may be related to different functional networks of lipids in memory mechanisms and differences in metabolic processes. The study underlines the importance of lipidomics in the pathophysiology of age-related cognitive decline. The necessity of evaluating the cognitive status of aged subjects by behavioral tests results in more specific detection of critical lipids in memory decline, on which now can be focused in subsequent memory studies in animals and humans.\n Copyright © 2020 Wackerlig, Köfeler, Korz, Hussein, Feyissa, Höger, Urban, Langer, Lubec and Lubec.\n\nKöfeler, Harald\n\n\n"
},
{
"text": "\n2081\nPrimary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma.\n\nCerroni, L\n\nSignoretti, S\n\nHöfler, G\n\nAnnessi, G\n\nPütz, B\n\nLackinger, E\n\nMetze, D\n\nGiannetti, A\n\nKerl, H\n\nBeiträge in Fachzeitschriften\nISI:A1997YD72100005\n9351568.0\n10.1097%2F00000478-199711000-00005\nNone\nRecently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.\n\nCerroni, Lorenzo\n\nHöfler, Gerald\n\nKerl, Helmut\n\n\n"
},
{
"text": "\n4100\nFirst clinical experience with the rapid-, short-acting amiodarone derivative E 047/1 after cardiac surgery.\n\nGombotz, H\n\nVicenzi, M\n\nMahla, E\n\nRehak, P\n\nMetzler, H\n\nBeiträge in Fachzeitschriften\nISI:000173708900004\n11913800.0\nNone\nNone\nBackground and objective: Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects. Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks. It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on haemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery.Methods: Testing E 047/1 was performed prospectively in two consecutive phase 11 open, clinical studies. Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, haemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg(-1) (pilot study, n = 15) or randomized to a 2 or 3 mg kg-1 bolus of E 047/1, followed by a 1 mg kg(-1) h(-1) continuous infusion for 2h (n = 10 in each group). Dysrhythmias, PQ, QTc intervals and haemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation.Results: At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per minute. Within the first 2-3 min of application in the pilot trial E 047/1 induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment. The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per hour. In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per hour after a 3 mg bolus. Approximately 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients. In only three patients did the incidence of dysrhythmias return to inclusion criteria levels. In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCWI in both groups. E 047/1 did not cause QTc prolongation.Conclusions: E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.\n\nMahla, Elisabeth\n\nMetzler, Helfried\n\nVicenzi, Martin\n\n\n"
},
{
"text": "\n134855\nThe peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells.\n\nDressel, U\n\nAllen, TL\n\nPippal, JB\n\nRohde, PR\n\nLau, P\n\nMuscat, GE\n\nBeiträge in Fachzeitschriften\nISI:000187072900008\n14525954.0\n10.1210/me.2003-0151\nNone\nLipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyl-transferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARbeta/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.\n\n\n"
},
{
"text": "\n182537\nPre-trained MRI-based Alzheimer's disease classification models to classify memory clinic patients.\n\nde Vos, F\n\nSchouten, TM\n\nKoini, M\n\nBouts, MJRJ\n\nFeis, RA\n\nLechner, A\n\nSchmidt, R\n\nvan Buchem, MA\n\nVerhey, FRJ\n\nOlde Rikkert, MGM\n\nScheltens, P\n\nde Rooij, M\n\nvan der Grond, J\n\nRombouts, SARB\n\nBeiträge in Fachzeitschriften\nISI:000561850400012\n32554321.0\n10.1016/j.nicl.2020.102303\nPMC7303669\nAnatomical magnetic resonance imaging (MRI), diffusion MRI and resting state functional MRI (rs-fMRI) have been used for Alzheimer's disease (AD) classification. These scans are typically used to build models for discriminating AD patients from control subjects, but it is not clear if these models can also discriminate AD in diverse clinical populations as found in memory clinics. To study this, we trained MRI-based AD classification models on a single centre data set consisting of AD patients (N = 76) and controls (N = 173), and used these models to assign AD scores to subjective memory complainers (N = 67), mild cognitive impairment (MCI) patients (N = 61), and AD patients (N = 61) from a multi-centre memory clinic data set. The anatomical MRI scans were used to calculate grey matter density, subcortical volumes and cortical thickness, the diffusion MRI scans were used to calculate fractional anisotropy, mean, axial and radial diffusivity, and the rs-fMRI scans were used to calculate functional connectivity between resting state networks and amplitude of low frequency fluctuations. Within the multi-centre memory clinic data set we removed scan site differences prior to applying the models. For all models, on average, the AD patients were assigned the highest AD scores, followed by MCI patients, and later followed by SMC subjects. The anatomical MRI models performed best, and the best performing anatomical MRI measure was grey matter density, separating SMC subjects from MCI patients with an AUC of 0.69, MCI patients from AD patients with an AUC of 0.70, and SMC patients from AD patients with an AUC of 0.86. The diffusion MRI models did not generalise well to the memory clinic data, possibly because of large scan site differences. The functional connectivity model separated SMC subjects and MCI patients relatively good (AUC = 0.66). The multimodal MRI model did not improve upon the anatomical MRI model. In conclusion, we showed that the grey matter density model generalises best to memory clinic subjects. When also considering the fact that grey matter density generally performs well in AD classification studies, this feature is probably the best MRI-based feature for AD diagnosis in clinical practice.\n Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.\n\nKoini, Marisa\n\nSchmidt, Reinhold\n\n\n"
}
]
}