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"text": "\n136577\nRetrospective Analysis of the Blood Component Utilization in a University Hospital of Maximum Medical Care.\n\nGeißler, RG\n\nFranz, D\n\nBuddendick, H\n\nKrakowitzky, P\n\nBunzemeier, H\n\nRoeder, N\n\nVan Aken, H\n\nKessler, T\n\nBerdel, W\n\nSibrowski, W\n\nSchlenke, P\n\nBeiträge in Fachzeitschriften\nISI:000303076300010\n22670131.0\n10.1159/000337956\nPMC3364044\nBACKGROUND: Demographic data illustrate clearly that people in highly developed countries get older, and the elderly need more blood transfusions than younger patients. Additionally, special extensive therapies result in an increased consumption of blood components. Beyond that the aging of the population reduces the total number of preferably young and healthy blood donors. Therefore, Patient Blood Management will become more and more important in order to secure an increasing blood supply under fair-minded conditions. METHODS: At the University Hospital of Münster (UKM) a comprehensive retrospective analysis of the utilization of all conventional blood components was performed including all medical and surgical disciplines. In parallel, a new medical reporting system was installed to provide a monthly analysis of the transfusional treatments in the whole infirmary, in every department, and in special blood-consuming cases of interest, as well. RESULTS: The study refers to all UKM in-patient cases from 2009 to 2011. It clearly demonstrates that older patients (>60 years, 35.2-35.7% of all cases, but 49.4-52.6% of all cases with red blood cell (RBC) transfusions, 36.4-41. 6% of all cases with platelet (PTL, apheresis only) transfusions, 45.2-48.0% of all cases with fresh frozen plasma (FFP) transfusions) need more blood products than younger patients. Male patients (54.4-63.9% of all cases with transfusions) are more susceptible to blood transfusions than female patients (36.1-45.6% of all cases with transfusions). Most blood components are used in cardiac, visceral, and orthopedic surgery (49.3-55.9% of all RBC units, 45.8-61.0% of all FFP units). When regarding medical disciplines, most transfusions are administered to hematologic and oncologic patients (12.9-17.7% of all RBC units, 9.2-12.0% of all FFP units). The consumption of PTL in this special patient cohort (40.6-50.9% of all PTL units) is more pronounced than in all other surgical or in non-surgical disciplines. CONCLUSION: The results obtained from our retrospective analysis may help to further optimize the responsible and medical indication-related utilization of blood transfusions as well as the recruitment of blood donors and their timing. It may be also a helpful tool in order to avoid needless transfusions and transfusionassociated adverse events.\n\nSchlenke, Peter\n\n\n"
},
{
"text": "\n170123\nInternational descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods.\n\nLütjohann, D\n\nBjörkhem, I\n\nFriedrichs, S\n\nKerksiek, A\n\nGeilenkeuser, WJ\n\nLövgren-Sandblom, A\n\nAnsorena, D\n\nAstiasarán, I\n\nBaila-Rueda, L\n\nBarriuso, B\n\nBretillon, L\n\nBrowne, RW\n\nCaccia, C\n\nCenarro, A\n\nCrick, PJ\n\nFauler, G\n\nGarcía-Llatas, G\n\nGriffiths, WJ\n\nIuliano, L\n\nLagarda, MJ\n\nLeoni, V\n\nLottenberg, AM\n\nMatysik, S\n\nMcDonald, J\n\nRideout, TC\n\nSchmitz, G\n\nNunes, VS\n\nWang, Y\n\nZerbinati, C\n\nDiczfalusy, U\n\nSchött, HF\n\nBeiträge in Fachzeitschriften\nISI:000446007300004\n30063945.0\n10.1016/j.biochi.2018.07.016\nNone\nIncreasing numbers of laboratories develop new methods based on gas-liquid and high-performance liquid chromatography to determine serum concentrations of oxygenated cholesterol metabolites such as 7α-, 24(S)-, and 27-hydroxycholesterol. We initiated a first international descriptive oxycholesterol (OCS) survey in 2013 and a second interventional survey 2014 in order to compare levels of OCS reported by different laboratories and to define possible sources of analytical errors. In 2013 a set of two lyophilized serum pools (A and B) was sent to nine laboratories in different countries for OCS measurement utilizing their own standard stock solutions. In 2014 eleven laboratories were requested to determine OCS concentrations in lyophilized pooled sera (C and D) utilizing the same provided standard stock solutions of OCS. The participating laboratories submitted results obtained after capillary gas-liquid chromatography-mass selective detection with either epicoprostanol or deuterium labelled sterols as internal standards and high-performance liquid chromatography with mass selective detection and deuterated OCS as internal standard. Each participant received a clear overview of the results in form of Youden-Plots and basic statistical evaluation in its used unit. The coefficients of variation of the concentrations obtained by all laboratories using their individual methods were 58.5-73.3% (survey 1), 56.8-60.3% (survey 2); 36.2-35.8% (survey 1), 56.6-59.8, (survey 2); 61.1-197.7% (survey 1), 47.2-74.2% (survey 2) for 24(S)-, 27-, and 7α-hydroxycholesterol, respectively. We are surprised by the very great differences between the laboratories, even under conditions when the same standards were used. The values of OCS's must be evaluated in relation to the analytical technique used, the efficiency of the ample separation and the nature of the internal standard used. Quantification of the calibration solution and inappropriate internal standards could be identified as major causes for the high variance in the reported results from the different laboratories. A harmonisation of analytical standard methods is highly needed.\n Copyright © 2018. Published by Elsevier B.V.\n\n\n"
},
{
"text": "\n182058\nMAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia.\n\nPlastira, I\n\nBernhart, E\n\nJoshi, L\n\nKoyani, CN\n\nStrohmaier, H\n\nReicher, H\n\nMalle, E\n\nSattler, W\n\nBeiträge in Fachzeitschriften\nISI:000530144300001\n32326963.0\n10.1186/s12974-020-01809-1\nPMC7178949\nIn the extracellular environment, lysophosphatidic acid (LPA) species are generated via autotaxin (ATX)-mediated hydrolysis of lysophospholipid precursors. Members of the LPA family are potent lipid mediators transmitting signals via six different G protein-coupled LPA receptors (LPAR1-6). The LPA signaling axis is indispensable for brain development and function of the nervous system; however, during damage of the central nervous system, LPA levels can increase and aberrant signaling events counteract brain function. Here, we investigated regulation of the ATX/LPA/LPAR axis in response to lipopolysaccharide-induced systemic inflammation in mice and potential neurotoxic polarization programs in LPA-activated primary murine microglia.\n In vivo, LPAR1-6 expression was established by qPCR in whole murine brain homogenates and in FACS-sorted microglia. ELISAs were used to quantitate LPA concentrations in the brain and cyto-/chemokine secretion from primary microglia in vitro. Transcription factor phosphorylation was analyzed by immunoblotting, and plasma membrane markers were analyzed by flow cytometry. We used MAPK inhibitors to study signal integration by the JNK, p38, and ERK1/2 branches in response to LPA-mediated activation of primary microglia.\n Under acute and chronic inflammatory conditions, we observed a significant increase in LPA concentrations and differential regulation of LPAR, ATX (encoded by ENPP2), and cytosolic phospholipase A2 (encoded by PLA2G4A) gene expression in the brain and FACS-sorted microglia. During pathway analyses in vitro, the use of specific MAPK antagonists (SP600125, SB203580, and PD98059) revealed that JNK and p38 inhibition most efficiently attenuated LPA-induced phosphorylation of proinflammatory transcription factors (STAT1 and -3, p65, and c-Jun) and secretion of IL-6 and TNFα. All three inhibitors decreased LPA-mediated secretion of IL-1β, CXCL10, CXCL2, and CCL5. The plasma membrane marker CD40 was solely inhibited by SP600125 while all three inhibitors affected expression of CD86 and CD206. All MAPK antagonists reduced intracellular COX-2 and Arg1 as well as ROS and NO formation, and neurotoxicity of microglia-conditioned media.\n In the present study, we show that systemic inflammation induces aberrant ATX/LPA/LPAR homeostasis in the murine brain. LPA-mediated polarization of primary microglia via MAPK-dependent pathways induces features reminiscent of a neurotoxic phenotype.\n\nBernhart, Eva Maria\n\nHinteregger, Helga\n\nJoshi, Lisha\n\nMalle, Ernst\n\nPlastira, Ioanna\n\nSattler, Wolfgang\n\nStrohmaier, Heimo\n\n\n"
},
{
"text": "\n187627\nEffect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.\n\nBakris, GL\n\nAgarwal, R\n\nAnker, SD\n\nPitt, B\n\nRuilope, LM\n\nRossing, P\n\nKolkhof, P\n\nNowack, C\n\nSchloemer, P\n\nJoseph, A\n\nFilippatos, G\n\nFIDELIO-DKD Investigators\n\nBeiträge in Fachzeitschriften\nNone\n33264825.0\n10.1056/NEJMoa2025845\nNone\nFinerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.\n In this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin-angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer's label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.\n During a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P = 0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P = 0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively).\n In patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.).\n Copyright © 2020 Massachusetts Medical Society.\n\nSourij, Harald\n\n\n"
},
{
"text": "\n1917\nPathophysiological mechanisms of the renin-angiotensin system and its pharmacologic modification by ACE inhibitors or angiotensin II (type 1) receptor blockers in cardiovascular diseases\n\nHuber, K\n\nPachinger, O\n\nPichler, M\n\nKlein, W\n\nBeiträge in Fachzeitschriften\nISI:A1997WX37300001\n9235795.0\n10.1007%2Fs003920050055\nNone\nAs a net effect of ACE-inhibitors and AT1-receptor antagonists on the renin-angiotensin system (RAS) cardioprotection due to vasodilative (reduction of blood pressure, afterload reduction), antiproliferative (reduced cell growth, reduction of "vascular" and/or "ventricular remodeling", reduced formation of extracellular matrix), as well as antiadrenergic actions and due to the stimulating effect on natriuresis, reduction of blood pressure, preload reduction can be expected. These aims of therapy have mostly been confirmed for the action of ACE-inhibitors by experimental and clinical studies but except for the treatment of arterial hypertension and few preliminary reports concerning the treatment of cardiac dysfunction, no comparable data are available for AT1-receptor antagonists. To date, an antithrombotic and profibrinolytic action could only be demonstrated for ACE-inhibitors. This effect has been discussed to be responsible for the improvement of long-term prognosis in patients with coronary artery disease. Despite the similar spectrum of action there exist important differences between ACE-inhibitors and AT1-receptor antagonists that might underline the need of an individual use of these drugs: the dual action of ACE-inhibitors on the RAS and the kinin system bears many benefits but has been also shown to be accompanied by side-effects, mainly chronic dry cough, in a relatively high percentage of patients thus leading to discontinuation of therapy in 8-14%. This respective side-effect can be prevented by the use of AT1-receptor antagonists. It has been discussed whether the incomplete action of ACE-inhibitors on AT1-receptor-mediated effects is at least in part responsible for the efficacy of this drug which is relatively high (75-80%) as compared to other substances. Due to their direct action, AT1-receptor-blockers might also be of high effectiveness for the treatment of severe heart failure. A combination of the ACE-inhibitor-mediated activation of the kinin-system with the more specific blockade of AT1-receptors by AT1-receptor antagonists might be of benefit and is currently under investigation. Finally, it has been discussed that the increased AT II concentration in case of AT1-receptor-blockade activates AT2-receptor-mediated mechanisms thus leading to an additive vasoprotective effect.\n\n\n"
},
{
"text": "\n6268\nEffect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.\n\nNeer, RM\n\nArnaud, CD\n\nZanchetta, JR\n\nPrince, R\n\nGaich, GA\n\nReginster, JY\n\nHodsman, AB\n\nEriksen, EF\n\nIsh-Shalom, S\n\nGenant, HK\n\nWang, O\n\nMitlak, BH (Study group members, Leb, G\n\nDobnig, H\n\nFahrleitner, A)\n\nBeiträge in Fachzeitschriften\nISI:000168554000004\n11346808.0\n10.1056%2FNEJM200105103441904\nNone\nBACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. METHODS: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. RESULTS: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). CONCLUSIONS: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.\n\nFahrleitner-Pammer, Astrid\n\n\n"
},
{
"text": "\n22202\nTreatment of humoral rejection after heart transplantation.\n\nGrauhan, O\n\nMüller, J\n\nv Baeyer, H\n\nVolk, HD\n\nFietze, E\n\nCohnert, T\n\nMeyer, R\n\nPfitzmann, R\n\nMansfeld, H\n\nSiniawski, H\n\nWarnecke, H\n\nHetzer, R\n\nBeiträge in Fachzeitschriften\nISI:000077747200006\n9883759.0\nNone\nNone\nBACKGROUND: Until a few years ago, the incidence of humoral rejection after heart transplantation was underestimated. These episodes were frequently very aggressive and often fatal, because the maintenance and emergency immunosuppression available at the time only inadequately covered the humoral branch of the immune response. In spite of individual case reports, the effects of blood purification procedures or cyclophosphamide in this situation can only be insufficiently estimated. METHODS: To evaluate this therapy concept, 20 dog-lymphocyte-antigen-matched dogs underwent heterotopic neck-heart transplantation. Fourteen dogs underwent transplantation after having been previously sensitized through multiple skin transplantations, 6 dogs were not sensitized (control). The animals received an induction with 3x 250 mg prednisolone, as well as triple immunosuppression (cyclosporine, azathioprine, and cortisone). Biopsy (light microscopy, immunofluorescence), intramyocardial voltage, electric myocardial impedance (>200 kHz, <10 kHz), and echocardiographic (left ventricular wall thickness, diastolic relaxation velocity) examinations were performed daily to monitor rejection. Rejection therapy was continued for 3 days according to the following regimen: apheresis, cortisone boluses (CB), and cyclophosphamide in group A1 (n = 4), apheresis and CB without cyclophosphamide in group A2 (n = 4), and CB only in group C (n = 6). The subsequent course under triple immunosuppression was then observed. RESULTS: In the sensitized animals the onset of severe humoral rejection on the fifth day deteriorated cardiac function down to 75% (70% to 80%) of the initial values. In groups A1 and A2, apheresis resulted in recovery to near-control values (89% to 94%) within two hours, and indeed to complete recovery (97% to 101%) after the second apheresis, that is, within 1 day. In group C recovery was delayed (2 days) and incomplete (84% to 91 %). After therapy was discontinued, rejection-related functional deterioration recurred immediately in group C, and from 2 to 3 days after apheresis, regardless of whether cyclophosphamide therapy was performed (group A1) or not (group A2). In the control group all animals showed a rejection-free posttransplantation course. CONCLUSIONS: By diluting inflammatory mediators, apheresis leads to a rapid improvement in cardiac function during severe humoral rejection after head transplantation. Neither apheresis nor cyclophosphamide therapy are able to have an immediate positive influence on the activation of the immune cascade and to prevent an ongoing rejection.\n\nCohnert, Tina Ulrike\n\n\n"
},
{
"text": "\n77918\nThe effect of exercise on the absorption of inhaled human insulin in healthy volunteers.\n\nPetersen, AH\n\nKohler, G\n\nKorsatko, S\n\nWutte, A\n\nWonisch, M\n\nMautner, A\n\nRonn, BB\n\nClauson, P\n\nLaursen, T\n\nWollmer, P\n\nPieber, TR\n\nBeiträge in Fachzeitschriften\nISI:000252773800005\n17764475.0\n10.1111/j.1365-2125.2007.03000.x\nPMC2291224\nWhat is already known about this subject: Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans. What this paper adds: This report is the first to investigate the effect of exercise on the absorption of inhaled insulin. In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged overall absorption. AIMS: To investigate the effect of moderate exercise on the absorption of inhaled insulin. METHODS: A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via a nebulizer and followed in random order by either 1) no exercise (NOEX), 2) 30 min exercise starting immediately after dosing (EX0), or 3) 30 min exercise starting 30 min after dosing (EX30). The study was carried out as a 10 h euglycaemic glucose clamp (90 mg dl(-1) (5.0 mmol l(-1))). RESULTS: The absorption of insulin over the first 2 h after start of exercise was 16% increased for EX0 (ratio (95%CI) 1.16 (1.04, 1.30), P = 0.01) and 20% increased for EX30 (1.20 (1.05, 1.36), P < 0.01), both compared with NOEX; the overall insulin absorption during 6 h and 10 h after dosing was not influenced by exercise. The maximum insulin concentration (C(max)) increased by 32% for EX0 and 35% for EX30 (both P < 0.01) compared with NOEX, while the time to C(max) was 31 min faster for EX0 (P < 0.01), but not significantly different after EX30, compared with NOEX. CONCLUSIONS: A significant and clinically relevant increase of insulin absorption over the first 2 h after the beginning of exercise was observed. Until data from studies using the specific insulin inhalers exists, patients using inhaled insulin should be made aware of a potential increased absorption and higher concentration of insulin in connection with exercise.\n\nKöhler, Gerd\n\nKorsatko, Stefan\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n116513\nCardiac movement identified on prehospital echocardiography predicts outcome in cardiac arrest patients.\n\nAichinger, G\n\nZechner, PM\n\nPrause, G\n\nSacherer, F\n\nWildner, G\n\nAnderson, CL\n\nPocivalnik, M\n\nWiesspeiner, U\n\nFox, JC\n\nBeiträge in Fachzeitschriften\nISI:000300788700010\n22235765.0\n10.3109/10903127.2011.640414\nNone\nThe prognostic value of emergency echocardiography (EE) in the management of cardiac arrest patients has previously been studied in an in-hospital setting. These studies mainly included patients who underwent cardiopulmonary resuscitation (CPR) by emergency medicine technicians at the scene and who arrived at the emergency department (ED) still in a state of cardiac arrest. In most European countries, cardiac arrest patients are normally treated by physician-staffed emergency medical services (EMS) teams on scene. Transportation to the ED while undergoing CPR is uncommon.\n To evaluate the ability of EE to predict outcome in cardiac arrest patients when it is performed by ultrasound-inexperienced emergency physicians on scene.\n We performed a prospective, observational study of nonconsecutive, nontrauma, adult cardiac arrest patients who were treated by physician-staffed urban EMS teams on scene. Participating emergency physicians (EPs) received a two-hour course in EE during CPR. After initial procedures were accomplished, EE was performed during a rhythm and pulse check. A single subxiphoid, four-chamber view was required for study enrollment. We defined sonographic evidence of cardiac kinetic activity as any detected motion of the myocardium, ranging from visible ventricular fibrillation to coordinated ventricular contractions. The CPR had to be continued for at least 15 minutes after the initial echocardiography. No clinical decisions were made based on the results of EE.\n Forty-two patients were enrolled in the study. The heart could be visualized successfully in all patients. Five (11.9%) patients survived to hospital admission. Of the 32 patients who had cardiac standstill on initial EE, only one (3.1%) survived to hospital admission, whereas four out of 10 (40%) patients with cardiac movement on initial EE survived to hospital admission (p = 0.008). Neither asystole on initial electrocardiogram nor peak capnography value, age, bystander CPR, or downtime was a significant predictor of survival. Only cardiac movement was associated with survival, and cardiac standstill at any time during CPR resulted in a positive predictive value of 97.1% for death at the scene.\n Our results support the idea of focused echocardiography as an additional criterion in the evaluation of outcome in CPR patients and demonstrate its feasibility in the prehospital setting.\n\nPocivalnik, Mirjam\n\nPrause, Gerhard\n\nWießpeiner, Ulrike Josefine\n\nWildner, Gernot\n\n\n"
},
{
"text": "\n153016\nThe AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients.\n\nRief, P\n\nPichler, M\n\nRaggam, R\n\nHafner, F\n\nGerger, A\n\nEller, P\n\nBrodmann, M\n\nGary, T\n\nBeiträge in Fachzeitschriften\nISI:000378053000023\n27310963.0\n10.1097/MD.0000000000003843\nPMC4998449\nThe aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI.In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9-28.23] vs median 4.3 mg/L [2.0-11.5]) and fibrinogen (median 427.5 mg/dL [344.25-530.0] vs 388.0 mg/dL [327.0-493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7-2.3) for CLI even after adjustment for other well-established vascular risk factors.An increased AAR is significantly associated with patients at high risk for CLI and other cardiovascular endpoints. The AAR is a broadly available and cheap marker, which might be useful to highlight patients at high risk for vascular endpoints.\n\nBrodmann, Marianne\n\nEller, Philipp\n\nGary, Thomas\n\nGerger, Armin\n\nHafner, Franz\n\nPichler, Martin\n\nRaggam, Reinhard Bernd\n\nRief, Peter\n\n\n"
},
{
"text": "\n168516\nStraight proximal humeral nailing: Risk of iatrogenic tendon injuries with respect to different entry points in anatomical specimens.\n\nSchwarz, AM\n\nHohenberger, GM\n\nEuler, S\n\nWeiglein, AH\n\nRiedl, R\n\nKuchling, S\n\nKrassnig, R\n\nPlecko, M\n\nBeiträge in Fachzeitschriften\nISI:000444908500005\n30017183.0\n10.1016/j.injury.2018.07.007\nNone\nThe purpose of the study was to evaluate the relationship of implant-related injuries to the adjacent anatomical structures in a newer generation straight proximal humeral nail (PHN) regarding different entry points. The proximity of the proximal lateral locking-screws of the MultiLoc proximal humeral nail (ML PHN) may cause iatrogenic tendon injuries to the lateral edge of the bicipital humeral groove (BG) as reference point for the tendon of the long head of biceps brachii (LBT) as well as the lateral insertion of the infraspinatus tendon (IST).\n The study comprised n = 40 upper extremities. Nail application was performed through a deltoid approach and supraspinatus tendon (SSP) split with a ML PHN. All tests were performed in three different entry points. First nail (N1) - standard position in line with the humeral shaft axis; second nail (N2) - a more lateral entry point; third alternative (N3) - medial position, centre of the humeral head. After nail placement, each specimen was screened for potential implant-related injuries or worded differently hit rates (HR) to the BG and the IST. The distances to the anatomical structures were measured and statistically interpreted.\n The observed iatrogenic IST injury rate was 17.5% (n = 7/40) for N1, 5% (n = 2/40) for N2 and 62.5% (n = 25/40) for N3, which was statistically significantly higher (p < 0.001). Regarding the BG, the evaluated HR was 7.5% (n = 3/40) for both N1 and N2. Only the nail placed in the head centre (N3) showed an iatrogenic injury rate of 20% (n = 8/40) (p < 0.062). No statistically significant association between humeral head size and the HR could be observed (head diameter: IST: p = 0.323, BG: p = 0.621; head circumference: IST: p = 0.167; BG: p = 0.940). For the IST and BG, all distances in nail positions N1 and N2 as well as N2 and N3 differ statistically significant (p < 0.001).\n An entry point for nail placement in line or slightly laterally to the humeral shaft axis - but still at the cartilage - should be advocated.\n Copyright © 2018 Elsevier Ltd. All rights reserved.\n\nHohenberger, Gloria\n\nKrassnig, Renate\n\nPlecko, Michael\n\nRiedl, Regina\n\nSchwarz, Angelika\n\n\n"
},
{
"text": "\n175356\nOrthopedic Injury Profiles in Adolescent Elite Athletes: A Retrospective Analysis From a Sports Medicine Department.\n\nCassel, M\n\nMüller, J\n\nMoser, O\n\nStrempler, ME\n\nReso, J\n\nMayer, F\n\nBeiträge in Fachzeitschriften\nISI:000467447800001\n31143127.0\n10.3389/fphys.2019.00544\nPMC6520583\nAim: The aim of the study was to identify common orthopedic sports injury profiles in adolescent elite athletes with respect to age, sex, and anthropometrics. Methods: A retrospective data analysis of 718 orthopedic presentations among 381 adolescent elite athletes from 16 different sports to a sports medical department was performed. Recorded data of history and clinical examination included area, cause and structure of acute and overuse injuries. Injury-events were analyzed in the whole cohort and stratified by age (11-14/15-17 years) and sex. Group differences were tested by chi-squared-tests. Logistic regression analysis was applied examining the influence of factors age, sex, and body mass index (BMI) on the outcome variables area and structure (α = 0.05). Results: Higher proportions of injury-events were reported for females (60%) and athletes of the older age group (66%) than males and younger athletes. The most frequently injured area was the lower extremity (47%) followed by the spine (30.5%) and the upper extremity (12.5%). Acute injuries were mainly located at the lower extremity (74.5%), while overuse injuries were predominantly observed at the lower extremity (41%) as well as the spine (36.5%). Joints (34%), muscles (22%), and tendons (21.5%) were found to be the most often affected structures. The injured structures were different between the age groups (p = 0.022), with the older age group presenting three times more frequent with ligament pathology events (5.5%/2%) and less frequent with bony problems (11%/20.5%) than athletes of the younger age group. The injured area differed between the sexes (p = 0.005), with males having fewer spine injury-events (25.5%/34%) but more upper extremity injuries (18%/9%) than females. Regression analysis showed statistically significant influence for BMI (p = 0.002) and age (p = 0.015) on structure, whereas the area was significantly influenced by sex (p = 0.005). Conclusion: Events of soft-tissue overuse injuries are the most common reasons resulting in orthopedic presentations of adolescent elite athletes. Mostly, the lower extremity and the spine are affected, while sex and age characteristics on affected area and structure must be considered. Therefore, prevention strategies addressing the injury-event profiles should already be implemented in early adolescence taking age, sex as well as injury entity into account.\n\nMoser, Othmar\n\n\n"
},
{
"text": "\n179077\nEnd-of-life decision making by Austrian physicians - a cross-sectional study.\n\nJahn-Kuch, D\n\nDomke, A\n\nBitsche, S\n\nStöger, H\n\nAvian, A\n\nJeitler, K\n\nPosch, N\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000512002100001\n31901225.0\n10.1186/s12904-019-0509-3\nPMC6942327\nAustria has recently been embroiled in the complex debate on the legalization of measures to end life prematurely. Empirical data on end-of-life decisions made by Austrian physicians barely exists. This study is the first in Austria aimed at finding out how physicians generally approach and make end-of-life therapy decisions.\n The European end-of-life decisions (EURELD) questionnaire, translated and adapted by Schildmann et al., was used to conduct this cross-sectional postal survey. Questions on palliative care training, legal issues, and use of and satisfaction with palliative care were added. All Austrian specialists in hematology and oncology, a representative sample of doctors specialized in internal medicine, and a sample of general practitioners, were invited to participate in this anonymous postal survey.\n Five hundred forty-eight questionnaires (response rate: 10.4%) were evaluated. 88.3% of participants had treated a patient who had died in the previous 12 months. 23% of respondents had an additional qualification in palliative medicine. The cause of death in 53.1% of patients was cancer, and 44.8% died at home. In 86.3% of cases, pain relief and / or symptom relief had been intensified. Further treatment had been withheld by 60.0%, and an existing treatment discontinued by 49.1% of respondents. In 5 cases, the respondents had prescribed, provided or administered a drug which had resulted in death. 51.3% of physicians said they would never carry out physician-assisted suicide (PAS), while 30.3% could imagine doing so under certain conditions. 38.5% of respondents supported the current prohibition of PAS, 23.9% opposed it, and 33.2% were undecided. 52.4% of physicians felt the legal situation with respect to measures to end life prematurely was ambiguous. An additional qualification in palliative medicine had no influence on measures taken, or attitudes towards PAS.\n The majority of doctors perform symptom control in terminally ill patients. PAS is frequently requested but rarely carried out. Attending physicians felt the legal situation was ambiguous. Physicians should therefore receive training in current legislation relating to end-of-life choices and medical decisions. The data collected in this survey will help political decision-makers provide the necessary legal framework for end-of-life medical care.\n\nAvian, Alexander\n\nJeitler, Klaus\n\nPosch, Nicole\n\nSiebenhofer-Kroitzsch, Andrea\n\nStoeger, Herbert\n\n\n"
},
{
"text": "\n185300\nUsing the RETAIN Tabletop Simulator as a Summative Assessment Tool for Neonatal Resuscitation Healthcare Professionals: A Pilot Study.\n\nGhoman, SK\n\nCutumisu, M\n\nSchmölzer, GM\n\nBeiträge in Fachzeitschriften\nNone\n33224907.0\n10.3389/fped.2020.569776\nPMC7674399\nBackground: Frequent and objective summative assessment of neonatal healthcare providers is important to ensure high-quality care to patients during neonatal resuscitation. Currently, neonatal resuscitation providers are only individually assessed using an at-home online multiple-choice questionnaire. While simulation-based assessment is preferred, resource constraints limit its widespread uptake. An alternative approach to simulation-based summative assessment is needed. Simulation-based serious games may provide a solution. Objective: The aim of this study was to examine if individual performance on the RETAIN (REsuscitation TrAINing for healthcare professionals) tabletop simulator can be used as a summative assessment of neonatal resuscitation providers, regardless of their prior board game experience. Method: Neonatal healthcare providers were recruited from a tertiary perinatal center to complete a (1) demographic pre-survey, (2) neonatal resuscitation scenario using an open-answer written pre-test, (3) neonatal resuscitation scenario using the RETAIN tabletop simulator, and (4) post-survey measuring usage and attitudes toward board games. Multiple linear regression analyses using the Johnson-Neyman technique were conducted in R to probe the moderation effect of years of board game on the relationship between pre-test and game performance. Results: Twenty Neonatal Resuscitation Program-trained healthcare providers (nurses, nurse practitioners, respiratory therapists, and fellows) were recruited for this study (n = 19 females). Participants' mean (standard deviation) pre-test score was 8.35 (1.81) out of a total 16 possible points (52%) and a score of 18 (4.41) out of a total of 40 possible points (45%) using RETAIN. Overall board game experience was 22.5 (12.6) years. Finally, years of board game moderated significantly the relation between the pre-test and game performance (B = -0.13, SE = 0.05, beta = -0.48, t = -2.77, p < 0.05; 95% CI [-0.24, -0.03]). Thus, participants' performance on the two tests (written and simulator) was significantly positively associated, but only for those who reported fewer than 21.5 years of board game experience. Conclusion: This study reports the preliminary results of a pilot study, indicating that the RETAIN tabletop simulator could be used as a simulation-based summative assessment, an enjoyable, low-cost alternative to traditional assessment approaches. RETAIN offers a solution to the need for more frequent and continued assessment of neonatal resuscitation providers.\n Copyright © 2020 Ghoman, Cutumisu and Schmölzer.\n\n\n"
},
{
"text": "\n186025\nPeriprosthetic fractures of hip and knee-A morbidity and mortality analysis.\n\nSmolle, MA\n\nHörlesberger, N\n\nMaurer-Ertl, W\n\nPuchwein, P\n\nSeibert, FJ\n\nLeithner, A\n\nBeiträge in Fachzeitschriften\nNone\n33536128.0\n10.1016/j.injury.2021.01.015\nNone\nPeriprosthetic fractures (PPF) following total knee (TKA) and hip arthroplasty (THA) have become more common over the years. The aim of the present study was to assess morbidity and mortality following surgery for PPF of hip and knee.\n Altogether, 124 patients (mean age: 77 years; 77.4% female) with PPF of the hip (n=97) and knee (n=27), treated between 2005 and 2017 at a level-1 trauma centre, were retrospectively included. In order to assess risk factors for postoperative morbidity, Fine and Gray's model was used to compensate for death as the competing event. Risk factors for mortality were estimated with uni- and multivariate Cox-regression models.\n Vancouver B2 fractures were most common (n=39; 42.4%), followed by B1 fractures (n=23; 25.0%). Lewis-Rorabeck Type I fractures (n=14; 51.9%) were most frequent in PPF of the knee. Overall complication rates were 44.0% and 29.9% for PPF of the knee and hip, respectively, with three patients having both early and late complications, 25 patients developing early complications and 19 patients undergoing surgery for implant-related, late complications. In the multivariate Fine and Gray model, advanced patient age (HR: 0.956; 95%CI: 0.922-0.991; p=0.014) and prosthesis exchange (vs. ORIF; HR: 0.242, 95%CI: 0.068-0.859; p=0.028) were associated with lower risk of implant-related complications, irrespective of gender (p=0.450) and a surgical delay > 2 days (p=0.411). One- and 5-year overall survival-rates were 97.9% and 93.1%, respectively. Gender, type of fixation (ORIF vs. prosthesis exchange), surgical delay > 2 days, BMI and age at surgery were neither in the univariate, nor multivariate Cox-regression model associated with an increased mortality rate.\n Postoperative morbidity caused by implant-related complications is higher in younger patients and those receiving ORIF. With the statistical approach used, potential underestimation of actual complication rates may have been avoided, taking into account death as the competing event. Despite being based on a retrospective, heterogenous patient collective treated at a level-1 trauma centre, our results indicate that careful planning of the surgical procedure beyond 2 days, taking into consideration both patient's age and activity level, has no negative effect on patient outcome.\n Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.\n\nHörlesberger, Nina\n\nLeithner, Andreas\n\nMaurer-Ertl, Werner\n\nPuchwein, Paul\n\nSeibert, Franz\n\nSmolle, Maria Anna\n\n\n"
},
{
"text": "\n52622\nBiased inhibition by a suramin analogue of A1-adenosine receptor/G protein coupling in fused receptor/G protein tandems: the A1-adenosine receptor is predominantly coupled to Goalpha in human brain.\n\nKudlacek, O\n\nWaldhoer, M\n\nKassack, MU\n\nNickel, P\n\nSalmi, JI\n\nFreissmuth, M\n\nNanoff, C\n\nBeiträge in Fachzeitschriften\nISI:000173202900002\n11862328.0\n10.1007/s00210-001-0493-y\nNone\nThe interface between receptors and G proteins can be considered as a drug target. Various classes of low molecular weight inhibitors have been identified that block the ability of receptors to interact with G proteins (e.g. peptides, suramin analogues and amphiphilic cations). Here we have tested if there are compounds that differentially affect the interaction of one receptor with two different (related) G protein alpha-subunits. Fusion proteins comprising the human A1-adenosine receptor and Galphai-1 (A1/Galphai-1) or Galphao (A1/Galphao) were expressed in HEK293 cells. Suramin analogues were screened for their ability to differentially affect high affinity binding of the agonist (-) N6-3-[125I](iodo-4-hydroxyphenylisopropyl) adenosine (IHPIA). One compound [NF326 = 8, '-(carbonylbis-(imino-3, -phenylenecarbonylimino))bis-(1-naphthol-3, -disulfonic acid, disodium salt)] was identified that inhibited high affinity agonist binding to the fusion protein A1/Galphai-1 but modestly enhanced binding of IHPIA to A1/Galphao. This action was specific because NF326 did not affect antagonist binding to either fusion protein. In addition, it was unrelated to a difference in affinity of the receptor for the G protein fusion moiety because the stability of ternary complexes formed by IHPIA + A1/Galphai-1 and IHPIA + A1/Galphao) is comparable and because lowering the affinity of the receptor for the G protein (by introducing point mutations at cys351 of Galphai-1) enhanced the uncoupling effect of NF326. Finally, NF326 did not discriminate between a fusion protein comprising the alpha2A-adrenoceptor and Galphai-1 (alpha2A)/Galphai-1) or Galphao-1 (alpha2A)/Galphao-1); binding of the agonist [3H]UK14304 (bromoxidine) to both fusion proteins was inhibited over a comparable concentration range while binding of the antagonist [3H]yohimbine was unaffected. These observations are consistent with the interpretation that the contact sites that are formed between individual receptors and G proteins differ. These differences suffice to allow for selective disruption by G protein inhibitors of different classes. Using NF326 we show that the bulk of the A1-adenosine receptors in human cerebrocortical membranes interacts with Galphao rather than Galphai.\n\n\n"
},
{
"text": "\n78764\nFurther evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome.\n\nRohkamm, B\n\nReilly, MM\n\nLochmuller, H\n\nSchlotter-Weigel, B\n\nBarisic, N\n\nSchols, L\n\nLaura, M\n\nJanecke, AR\n\nMiltenberger-Miltenyi, G\n\nJohn, E\n\nFischer, C\n\nGrill, F\n\nWakeling, W\n\nDavis, M\n\nPieber, TR\n\nAuer-Grumbach, M\n\nNicholson, G\n\nPareyson, D\n\nBeiträge in Fachzeitschriften\nISI:000253671700017\n17663003.0\n10.1016/j.jns.2007.06.047\nPMC3272403\nOBJECTIVE: Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. Mutations in the heat-shock proteins HSPB1 and HSPB8 can cause related distal hereditary motor neuropathies (dHMN) and are considered candidates for dHMN-V, CMT2, and SS. DESIGN: To define the frequency and distribution of mutations in the GARS, BSCL2, HSPB1 and HSPB8 genes we screened 33 unrelated sporadic and familial patients diagnosed as either dHMN-V, CMT2D or SS. Exon 3 of the BSCL2 gene was screened in further 69 individuals with an unclassified dHMN phenotype or diagnosed as hereditary spastic paraplegia (HSP) complicated by pure motor neuropathy. RESULTS: Four patients diagnosed with dHMN-V or SS carried known heterozygous BSCL2 mutations (N88S and S90L). In one dHMN-V patient we detected a putative GARS mutation (A57V). No mutations were detected in HSPB1 and HSPB8. The diagnostic yield gained in the series of 33 probands was 12% for BSCL2 mutations and 3% for GARS mutations. In the series of unclassified dHMN and complicated HSP cases no mutations were found. CONCLUSIONS: Our data confirm that most likely only two mutations (N88S, S90L) in exon 3 of BSCL2 may lead to dHMN-V or SS phenotypes. Mutations in GARS, HSPB1 and HSPB8. are not a common cause of dHMN-V, SS and CMT2D. We would therefore suggest that a genetic testing of dHMN-V and SS patients should begin with screening of exon 3 of the BSCL2 gene. Screening of the GARS gene is useful in patients with CMT2 with predominant hand involvement and dHMN-V. The rather low frequencies of BSCL2, GARS, HSPB1 and HSPB8 mutations in dHMN-V, CMT2D and SS patients strongly point to further genetic heterogeneity of these related disorders.\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n138559\nCasebook: a virtual patient iPad application for teaching decision-making through the use of electronic health records.\n\nBloice, MD\n\nSimonic, KM\n\nHolzinger, A\n\nBeiträge in Fachzeitschriften\nISI:000341055200001\n25100051.0\n10.1186/1472-6947-14-66\nPMC4149039\nVirtual Patients are a well-known and widely used form of interactive software used to simulate aspects of patient care that students are increasingly less likely to encounter during their studies. However, to take full advantage of the benefits of using Virtual Patients, students should have access to multitudes of cases. In order to promote the creation of collections of cases, a tablet application was developed which makes use of electronic health records as material for Virtual Patient cases. Because electronic health records are abundantly available on hospital information systems, this results in much material for the basis of case creation.\n An iPad-based Virtual Patient interactive software system was developed entitled Casebook. The application has been designed to read specially formatted patient cases that have been created using electronic health records, in the form of X-ray images, electrocardiograms, lab reports, and physician notes, and present these to the medical student. These health records are organised into a timeline, and the student navigates the case while answering questions regarding the patient along the way. Each health record can also be annotated with meta-information by the case designer, such as insight into the thought processes and the decision-making rationale of the physician who originally worked with the patient. Students learn decision-making skills by observing and interacting with real patient cases in this simulated environment. This paper discusses our approach in detail.\n Our group is of the opinion that Virtual Patient cases, targeted at undergraduate students, should concern patients who exhibit prototypical symptoms of the kind students may encounter when beginning their first medical jobs. Learning theory research has shown that students learn decision-making skills best when they have access to multitudes of patient cases and it is this plurality that allows students to develop their illness scripts effectively. Casebook emphasises the use of pre-existing electronic health record data as the basis for case creation, thus, it is hoped, making it easier to produce cases in larger numbers. By creating a Virtual Patient system where cases are built from abundantly available electronic health records, collections of cases can be accumulated by institutions.\n\nBloice, Marcus\n\nHolzinger, Andreas\n\nSimonic, Klaus-Martin\n\n\n"
},
{
"text": "\n183877\nReduced mitochondrial resilience enables non-canonical induction of apoptosis after TNF receptor signaling in virus-infected hepatocytes.\n\nLampl, S\n\nJanas, MK\n\nDonakonda, S\n\nBrugger, M\n\nLohr, K\n\nSchneider, A\n\nManske, K\n\nSperl, LE\n\nKläger, S\n\nKüster, B\n\nWettmarshausen, J\n\nMüller, C\n\nLaschinger, M\n\nHartmann, D\n\nHüser, N\n\nPerocchi, F\n\nSchmitt-Kopplin, P\n\nHagn, F\n\nZender, L\n\nHornung, V\n\nBorner, C\n\nPichlmair, A\n\nKashkar, H\n\nKlingenspor, M\n\nPrinz, M\n\nSchreiner, S\n\nConrad, M\n\nJost, PJ\n\nZischka, H\n\nSteiger, K\n\nKrönke, M\n\nZehn, D\n\nProtzer, U\n\nHeikenwälder, M\n\nKnolle, PA\n\nWohlleber, D\n\nBeiträge in Fachzeitschriften\nISI:000590263100013\n32598967.0\n10.1016/j.jhep.2020.06.026\nNone\nSelective elimination of virus-infected hepatocytes occurs through virus-specific CD8 T cells recognizing peptide-loaded MHC molecules. Herein, we report that virus-infected hepatocytes are also selectively eliminated through a cell-autonomous mechanism.\n We generated recombinant adenoviruses and genetically modified mouse models to identify the molecular mechanisms determining TNF-induced hepatocyte apoptosis in vivo and used in vivo bioluminescence imaging, immunohistochemistry, immunoblot analysis, RNAseq/proteome/phosphoproteome analyses, bioinformatic analyses, mitochondrial function tests.\n We found that TNF precisely eliminated only virus-infected hepatocytes independently of local inflammation and activation of immune sensory receptors. TNF receptor I was equally relevant for NF-kB activation in healthy and infected hepatocytes, but selectively mediated apoptosis in infected hepatocytes. Caspase 8 activation downstream of TNF receptor signaling was dispensable for apoptosis in virus-infected hepatocytes, indicating an unknown non-canonical cell-intrinsic pathway promoting apoptosis in hepatocytes. We identified a unique state of mitochondrial vulnerability in virus-infected hepatocytes as the cause for this non-canonical induction of apoptosis through TNF. Mitochondria from virus-infected hepatocytes showed normal biophysical and bioenergetic functions but were characterized by reduced resilience to calcium challenge. In the presence of unchanged TNF-induced signaling, reactive oxygen species-mediated calcium release from the endoplasmic reticulum caused mitochondrial permeability transition and apoptosis, which identified a link between extrinsic death receptor signaling and cell-intrinsic mitochondrial-mediated caspase activation.\n Our findings reveal a novel concept in immune surveillance by identifying a cell-autonomous defense mechanism that selectively eliminates virus-infected hepatocytes through mitochondrial permeability transition.\n The liver is known for its unique immune functions. Herein, we identify a novel mechanism by which virus-infected hepatocytes can selectively eliminate themselves through reduced mitochondrial resilience to calcium challenge.\n Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nJost, Philipp\n\n\n"
},
{
"text": "\n2351\nShort-course therapy with amoxycillin-clarithromycin triple therapy for 10 days (ACT-10) eradicates Helicobacter pylori and heals duodenal ulcer. ACT-10 Study Group.\n\nWurzer, H\n\nRodrigo, L\n\nStamler, D\n\nArchambault, A\n\nRokkas, T\n\nSkandalis, N\n\nFedorak, R\n\nBazzoli, F\n\nHentschel, E\n\nMora, P\n\nArchimandritis, A\n\nMegraud, F\n\nBeiträge in Fachzeitschriften\nISI:A1997YB84000017\n9354205.0\n10.1046%2Fj.1365-2036.1997.00223.x\nNone\nBACKGROUND: Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved. METHODS: Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4-6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4-6 weeks. RESULTS: Two hundred and sixty-seven (267) patients were randomized to ACT-10 (n = 137) or Dual therapy (n = 130). By per-protocol and intention-to-treat analyses, H. pylori eradication at 4-6 weeks follow-up was 91% (115/127) and 88% (120/136), respectively, for ACT-10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P < 0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT-10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre-treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT-10 and in 25% of those receiving Dual therapy. ACT-10 and Dual therapy patients experienced similar rates of drug-related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication. CONCLUSION: In patients with active duodenal ulcer, a 10-day course of amoxycillin-clarithromycin-based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.\n\n\n"
}
]
}