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"text": "\n173703\nCoagulation changes induced by lower-body negative pressure in men and women.\n\nCvirn, G\n\nWaha, JE\n\nBrix, B\n\nRössler, A\n\nJantscher, A\n\nSchlagenhauf, A\n\nKoestenberger, M\n\nWonisch, W\n\nWagner, T\n\nGoswami, N\n\nBeiträge in Fachzeitschriften\nISI:000468207400005\n30763159.0\n10.1152/japplphysiol.00940.2018\nNone\nWe investigated whether lower-body negative pressure (LBNP) application leads to coagulation activation in whole blood (WB) samples in healthy men and women. Twenty-four women and 21 men, all healthy young participants, with no histories of thrombotic disorders and not on medications, were included. LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both men and women using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. LBNP led to coagulation activation determined in both plasma and WB samples. At baseline, women were hypercoagulable compared with men, as evidenced by their shorter "lag times" and higher thrombin peaks and by shorter "coagulation times" and "clot formation times." Moreover, men were more susceptible to LBNP, as reflected in their elevated factor VIII levels and decreased lag times following LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. Women appear to be relatively hypercoagulable compared with men, but men are more susceptible to coagulation changes during LBNP. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis. NEW & NOTEWORTHY LBNP led to coagulation activation determined in both plasma and whole blood samples. At baseline, women were hypercoagulable compared with men. Men were, however, more susceptible to coagulation changes during LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis.\n\nBrix, Bianca\n\nCvirn, Gerhard\n\nGoswami, Nandu\n\nJantscher, Andreas\n\nKoestenberger, Martin\n\nRössler, Andreas\n\nSchlagenhauf, Axel\n\nWagner, Thomas\n\nWaha, James Elvis\n\nWonisch, Willibald\n\n\n"
},
{
"text": "\n177452\nEukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer.\n\nGolob-Schwarzl, N\n\nWodlej, C\n\nKleinegger, F\n\nGogg-Kamerer, M\n\nBirkl-Toeglhofer, AM\n\nPetzold, J\n\nAigelsreiter, A\n\nThalhammer, M\n\nPark, YN\n\nHaybaeck, J\n\nBeiträge in Fachzeitschriften\nISI:000491944600006\n31586263.0\n10.1007/s00432-019-03030-x\nPMC6800842\nGallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers. The study focus was the role of eIF6 (an anti-association factor for the ribosomal subunits) in GBC.\n In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR).\n High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis.\n Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.\n\nAigelsreiter, Ariane\n\nBirkl-Töglhofer, Anna Maria\n\nGolob-Schwarzl, Nicole\n\nHaybäck, Johannes\n\nSkofler, Christina\n\nThalhammer, Michael\n\n\n"
},
{
"text": "\n181104\nEnhanced cutinase-catalyzed hydrolysis of polyethylene terephthalate by covalent fusion to hydrophobins.\n\nRibitsch, D\n\nHerrero Acero, E\n\nPrzylucka, A\n\nZitzenbacher, S\n\nMarold, A\n\nGamerith, C\n\nTscheließnig, R\n\nJungbauer, A\n\nRennhofer, H\n\nLichtenegger, H\n\nAmenitsch, H\n\nBonazza, K\n\nKubicek, CP\n\nDruzhinina, IS\n\nGuebitz, GM\n\nBeiträge in Fachzeitschriften\nISI:000353912000001\n25795674.0\n10.1128/AEM.04111-14\nPMC4421044\nCutinases have shown potential for hydrolysis of the recalcitrant synthetic polymer polyethylene terephthalate (PET). We have shown previously that the rate of this hydrolysis can be enhanced by the addition of hydrophobins, small fungal proteins that can alter the physicochemical properties of surfaces. Here we have investigated whether the PET-hydrolyzing activity of a bacterial cutinase from Thermobifida cellulosilytica (Thc_Cut1) would be further enhanced by fusion to one of three Trichoderma hydrophobins, i.e., the class II hydrophobins HFB4 and HFB7 and the pseudo-class I hydrophobin HFB9b. The fusion enzymes exhibited decreased kcat values on soluble substrates (p-nitrophenyl acetate and p-nitrophenyl butyrate) and strongly decreased the hydrophilicity of glass but caused only small changes in the hydrophobicity of PET. When the enzyme was fused to HFB4 or HFB7, the hydrolysis of PET was enhanced >16-fold over the level with the free enzyme, while a mixture of the enzyme and the hydrophobins led only to a 4-fold increase at most. Fusion with the non-class II hydrophobin HFB9b did not increase the rate of hydrolysis over that of the enzyme-hydrophobin mixture, but HFB9b performed best when PET was preincubated with the hydrophobins before enzyme treatment. The pattern of hydrolysis by the fusion enzymes differed from that of Thc_Cut1 as the concentration of the product mono(2-hydroxyethyl) terephthalate relative to that of the main product, terephthalic acid, increased. Small-angle X-ray scattering (SAXS) analysis revealed an increased scattering contrast of the fusion proteins over that of the free proteins, suggesting a change in conformation or enhanced protein aggregation. Our data show that the level of hydrolysis of PET by cutinase can be significantly increased by fusion to hydrophobins. The data further suggest that this likely involves binding of the hydrophobins to the cutinase and changes in the conformation of its active center. \n Copyright © 2015, American Society for Microbiology. All Rights Reserved.\n\n\n"
},
{
"text": "\n185152\nInflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism.\n\nScharrer, S\n\nPrimas, C\n\nEichinger, S\n\nTonko, S\n\nKutschera, M\n\nKoch, R\n\nBlesl, A\n\nReinisch, W\n\nMayer, A\n\nHaas, T\n\nFeichtenschlager, T\n\nFuchssteiner, H\n\nSteiner, P\n\nLudwiczek, O\n\nPlatzer, R\n\nMiehsler, W\n\nTillinger, W\n\nApostol, S\n\nSchmid, A\n\nSchweiger, K\n\nVogelsang, H\n\nDejaco, C\n\nHerkner, H\n\nNovacek, G\n\nBeiträge in Fachzeitschriften\nNone\n33386735.0\n10.1093/ibd/izaa337\nNone\nLittle is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE.\n This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used.\n We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events.\n The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.\n © 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.\n\nBlesl, Andreas\n\n\n"
},
{
"text": "\n1214\nHomozygous gene deletions of the glutathione S-transferases M1 and T1 are associated with thimerosal sensitization.\n\nWestphal, GA\n\nSchnuch, A\n\nSchulz, TG\n\nReich, K\n\nAberer, W\n\nBrasch, J\n\nKoch, P\n\nWessbecher, R\n\nSzliska, C\n\nBauer, A\n\nHallier, E\n\nBeiträge in Fachzeitschriften\nISI:000089088300005\n11007341.0\n10.1007%2Fs004200000159\nNone\nOBJECTIVE: Thimerosal is an important preservative in vaccines and ophthalmologic preparations. The substance is known to be a type IV sensitizing agent. High sensitization rates were observed in contact-allergic patients and in health care workers who had been exposed to thimerosal-preserved vaccines. There is evidence for the involvement of the glutathione system in the metabolism of thimerosal or its decomposition products (organomercury alkyl compounds). Thus detoxification by polymorphically expressed glutathione S-transferases such as GSTT1 and GSTM1 might have a protective effect against sensitization by these substances. METHODS: To address this question, a case control study was conducted, including 91 Central European individuals with a positive patch-test reaction to thimerosal. This population was compared with 169 healthy controls and additionally with 114 individuals affected by an allergy against para-substituted aryl compounds. The latter population was included in order to test whether possible associations were due to substance-specific effects, or were a general feature connected with type IV immunological diseases. Homozygous deletions of GSTT1 and GSTM1 were determined by polymerase chain reaction. RESULTS: Glutathione S-transferase M1 deficiency was significantly more frequent among patients sensitized to thimerosal (65.9%, P = 0.013) compared with the healthy control group (49.1%) and the "para-compound" group (48%, P = 0.034). Glutathione S-transferase T1 deficiency in the thimerosal/mercury group (19.8%) was barely elevated versus healthy controls (16.0%) and the "para-compound" group (14.0%). The combined deletion (GSTT1-/GSTM1-) was markedly more frequent among thimerosal-sensitized patients than in healthy controls (17.6% vs. 6.5%, P = 0.0093) and in the "para-compound" group (17.6% vs. 6.1%, P =0.014), revealing a synergistic effect of these enzyme deficiencies (healthy controls vs. thimerosal GSTM1 negative individuals, OR = 2.0 [CI = 1.2-3.4], GSTT1-, OR = 1.2 [CI = 0.70-2.1], GSTM1/T1-, OR = 3.1 [CI = 1.4-6.5]). CONCLUSIONS: Since the glutathione-dependent system was repeatedly shown to be involved in the metabolism of thimerosal decomposition products, the observed association may be of functional relevance.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n2096\nPrognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia.\n\nKaddu, S\n\nSmolle, J\n\nCerroni, L\n\nKerl, H\n\nBeiträge in Fachzeitschriften\nISI:A1996VZ91500001\n9001978.0\n10.1111/j.1600-0560.1996.tb01440.x\nNone\nThe relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42-83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or bandlike (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p < 0.01; z = 5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.\n\nCerroni, Lorenzo\n\nKaddu, Steven\n\nKerl, Helmut\n\nSmolle, Josef\n\n\n"
},
{
"text": "\n22738\nEvaluation of HLA-DR expression and T-lymphocyte infiltration in osteosarcoma.\n\nTrieb, K\n\nLechleitner, T\n\nLang, S\n\nWindhager, R\n\nKotz, R\n\nDirnhofer, S\n\nBeiträge in Fachzeitschriften\nISI:000076587700002\n9820863.0\n10.1016/S0344-0338(98)80126-X\nNone\nAlthough in recent years the outcome of patients with osteosarcoma has considerably been improved by combining neoadjuvant chemotherapy with radical surgery, there still remains the problem of nonresponse to chemotherapy. T-lymphocytes play a critical role in tumor immunology, and MHC molecules are of central importance in the regulation of the immune response. It is the aim of this study to investigate whether T-lymphocyte infiltration of osteosarcomas and HLA-DR expression on tumor cells and infiltrating immune cells are of predictive or diagnostic value. Expression of CD3, CD8 and HLA-II was evaluated immunohistochemically on paraffin-embedded sections of 35 patients with high-grade osteosarcoma at the time of biopsy before chemotherapy and correlated with histologic response to chemotherapy, tumor size, age, alkaline-phosphatase serum levels and duration of symptoms. Thirty-four patients with osteoblastoma (n = 7), osteoid osteoma (n = 7) or fibrous dysplasia (n = 20) served as controls. Osteosarcomas were infiltrated by CD3+ (33/35, 95%) and CD8+ T-lymphocytes (24/35, 68%), non malignant bone tumors by CD3+ in 91% (31/34) and CD8+ T-lymphocytes in 74% (25/34), respectively. T-lymphocytes were positive for HLA-DR expression in 29% (10/35) in osteosarcomas and in 11% (4/34) in non-malignant controls. Osteosarcoma cells were positive for HLA-DR in 11/35 (31%) and non-malignant tumor cells in only 9% (3/34). Therefore, HLA-DR is overexpressed in osteosarcoma (p < 0.05). HLA-DR expression on osteosarcoma cells showed a positive correlation with HLA-DR expression on lymphocytes (p < 0.001) as well as with duration of symptoms and age (p < 0.05). Response to preoperative chemotherapy, gender, tumor size and serum alkaline-phosphatase levels did not correlate with the expression of the molecules tested. Our results show that HLA-DR is overexpressed in osteosarcoma cells compared to non-malignant bone-tumors. This overexpression, however, fails to serve as a predictive marker for response to neoadjuvant chemotherapy. The same is also true for tumor-infiltrating lymphocytes expressing CD3, CD8 and HLA-DR. Increased HLA-DR expression in osteosarcoma is most likely due to the immune response against the tumor.\n\n\n"
},
{
"text": "\n65939\nDetermination of pravastatin by high performance liquid chromatography.\n\nSiekmeier, R\n\nGross, W\n\nMärz, W\n\nBeiträge in Fachzeitschriften\nISI:000089254200001\n11020028.0\nNone\nNone\nBACKGROUND: Pravastatin is a hydrophilic liver-specific inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. It effectively lowers plasma cholesterol and low-density lipoprotein concentrations in humans. Pharmacokinetic studies of pravastatin have been mostly performed by means of radioactively labelled drug or by measuring plasma concentrations with gas chromatography and mass spectrometry. AIMS OF THE STUDY: Aim of our study was to develop a simple, but reliable method which allows the determination of pravastatin plasma concentrations under clinical routine conditions. SUBJECTS, MATERIALS AND METHODS: Samples were prepared by solid-phase extraction on cyclohexyl bond elut cartridges. Chromatography was carried out on an octyl matrix. Triamcinolone acetonide was used as internal standard. The method was linear within the range of 5 to 200 microg/l pravastatin. The coefficient of variation depended on the pravastatin concentration, but was less than 10% throughout. The pharmacokinetics of pravastatin were determined in healthy individuals. Five healthy subjects received single oral doses of pravastatin (60 mg) and one of these subjects additionally received a dose of 80 mg at three different study days. In all subjects blood was sampled 0, 30, 60, 90, 120, 150, 180, 240 and 300 min after drug intake. RESULTS: Peak plasma concentrations of pravastatin were found between 60 min and 120 min after oral administration of 60 mg and reached values between 37 microg/l and 126 microg/l. The calculated AUCs were between 52 ng/ml x h and 311 ng/ml x h and the corresponding plasma elimination half-life times were between 95 min and 165 min. In all subjects plasma concentrations of pravastatin 5 hours after oral drug administration were near the detection limit of the method (5 microg/l). Intraindividually, there was only little variation in the kinetics of pravastatin. However, marked differences were encountered between the subjects studied. CONCLUSION: The data suggest that the determination of pravastatin plasma concentrations by means of a HPLC system can be used for routine analysis of pravastatin plasma concentrations. The obtained pharmacokinetic data in healthy individuals stand in ample agreement with the results of prior studies in which the concentrations of pravastatin were determined by other more sophisticated methods.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n90030\nOral status among seniors in nine nursing homes in Styria, Austria.\n\nGluhak, C\n\nArnetzl, GV\n\nKirmeier, R\n\nJakse, N\n\nArnetzl, G\n\nBeiträge in Fachzeitschriften\nISI:000274667100008\n19371391.0\n10.1111/j.1741-2358.2009.00281.x\nNone\nTo investigate the oral state in participants cared for in residences for senior citizens in Styria, Austria.\n Four hundred and nine participants in Styria from nine homes for senior citizens were examined employing parameters in accordance with those of Folstein's Mini Mental Status (MMS), DMFT, basic periodontal examination, the modified oral hygiene index, pain experienced during the preceding year, the subjective and objective need for treatment, and also requirements involving surgical and prosthetic treatment. Furthermore, the habitual methods of maintaining oral hygiene were examined establishing by whom this was carried out - whether by the patient, the nurse, or by patient and nurse together.\n Four hundred and nine participants were examined, 48.3% were found to have retained on average 4.9 of their own teeth while 69% were fitted with dentures; however, 81% of the participants required prosthetic treatment. 28.9% of the participants had experienced acute dental pain during the preceding year and surgical treatment was found to be necessary in 47.7% of those with original teeth. Eighty-four per cent of the participants showed acute inflammation of the periodontium while the state of oral hygiene, measured on a scale of 0-4, reached an average of 2.43. Oral hygiene was carried out by the nurses in only 7.46% of the cases which showed an average MMS measurement of 18.\n The results compared with those reported in other recent surveys and our data show an urgent need in Austria to improve the standards in dental care for the hospitalised elderly. Regular dental checks, carried out in the actual home by a dental surgeon should be introduced, whilst the nursing staff should be made fully aware of the problems caused by insufficient oral care and receive regular support from specialised oral hygiene assistants. The results of this survey also suggest that nursing staff should be equipped with simple instruments in order to judge to the extent to which the patient is capable of carrying out oral care independently and then according to the results to supplement this with additional care.\n\nJakse, Norbert\n\n\n"
},
{
"text": "\n95606\nTriangular osteosynthesis and iliosacral screw fixation for unstable sacral fractures: a cadaveric and biomechanical evaluation under cyclic loads.\n\nSchildhauer, TA\n\nLedoux, WR\n\nChapman, JR\n\nHenley, MB\n\nTencer, AF\n\nRoutt, MLC\n\nBeiträge in Fachzeitschriften\nISI:000180117400004\n12499964.0\n10.1097/00005131-200301000-00004\nNone\nOBJECTIVE: To conduct a biomechanical comparison of a new triangular osteosynthesis and the standard iliosacral screw osteosynthesis for unstable transforaminal sacral fractures in the immediate postoperative situation as well as in the early postoperative weight-bearing period. DESIGN: Twelve preserved human cadaveric lumbopelvic specimens were cyclicly tested in a single-limb-stance model. A transforaminal sacral fracture combined with ipsilateral superior and inferior pubic rami fractures were created and stabilized. Loads simulating muscle forces and body weight were applied. Fracture site displacement in three dimensions was evaluated using an electromagnetic motion sensor system. INTERVENTION: Specimens were randomly assigned to either an iliosacral and superior pubic ramus screw fixation or to a triangular osteosynthesis consisting of lumbopelvic stabilization (between L5 pedicle and posterior ilium) combined with iliosacral and superior pubic ramus screw fixation. MAIN OUTCOME MEASURES: Peak loaded displacement at the fracture site was measured for assessment of initial stability. Macroscopic fracture behavior through 10, 00 cycles of loading, simulating the early postoperative weight-bearing period, was classified into type 1 with minimal motion at the fracture site, type 2 with complete displacement of the inferior pubic ramus, or type 3 with catastrophic failure. RESULTS: The triangular osteosynthesis had a statistically significantly smaller displacement under initial peak loads (mean +/- standard deviation [SD], 0.163 +/- 0.073 cm) and therefore greater initial stability than specimens with the standard iliosacral screw fixation (mean +/- SD, 0.611 +/- 0.453 cm) ( = 0.0104), independent of specimen age or sex. All specimens with the triangular osteosynthesis demonstrated type 1 fracture behavior, whereas iliosacral screw fixation resulted in one type 1, two type 2, and three type 3 fracture behaviors before or at 10, 00 cycles of loading. CONCLUSION: Triangular osteosynthesis for unstable transforaminal sacral fractures provides significantly greater stability than iliosacral screw fixation under in vitro cyclic loading conditions. In vitro cyclic loading, as a limited simulation of early stages of patient mobilization in the postoperative period, allows for a time-dependent evaluation of any fracture fixation system.\n\n\n"
},
{
"text": "\n132411\nDysfunctional nitric oxide signalling increases risk of myocardial infarction.\n\nErdmann, J\n\nStark, K\n\nEsslinger, UB\n\nRumpf, PM\n\nKoesling, D\n\nde Wit, C\n\nKaiser, FJ\n\nBraunholz, D\n\nMedack, A\n\nFischer, M\n\nZimmermann, ME\n\nTennstedt, S\n\nGraf, E\n\nEck, S\n\nAherrahrou, Z\n\nNahrstaedt, J\n\nWillenborg, C\n\nBruse, P\n\nBrænne, I\n\nNöthen, MM\n\nHofmann, P\n\nBraund, PS\n\nMergia, E\n\nReinhard, W\n\nBurgdorf, C\n\nSchreiber, S\n\nBalmforth, AJ\n\nHall, AS\n\nBertram, L\n\nSteinhagen-Thiessen, E\n\nLi, SC\n\nMärz, W\n\nReilly, M\n\nKathiresan, S\n\nMcPherson, R\n\nWalter, U\n\nCARDIoGRAM\n\nOtt, J\n\nSamani, NJ\n\nStrom, TM\n\nMeitinger, T\n\nHengstenberg, C\n\nSchunkert, H\n\nBeiträge in Fachzeitschriften\nISI:000328575300051\n24213632.0\n10.1038/nature12722\nNone\nMyocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n133831\nDisease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.\n\nMoinzadeh, P\n\nAberer, E\n\nAhmadi-Simab, K\n\nBlank, N\n\nDistler, JH\n\nFierlbeck, G\n\nGenth, E\n\nGuenther, C\n\nHein, R\n\nHenes, J\n\nHerich, L\n\nHerrgott, I\n\nKoetter, I\n\nKreuter, A\n\nKrieg, T\n\nKuhr, K\n\nLorenz, HM\n\nMeier, F\n\nMelchers, I\n\nMensing, H\n\nMueller-Ladner, U\n\nPfeiffer, C\n\nRiemekasten, G\n\nSárdy, M\n\nSchmalzing, M\n\nSunderkoetter, C\n\nSusok, L\n\nTarner, IH\n\nVaith, P\n\nWorm, M\n\nWozel, G\n\nZeidler, G\n\nHunzelmann, N\n\nall participating DNSS centers\n\nBeiträge in Fachzeitschriften\nISI:000351615700018\n24389298.0\n10.1136/annrheumdis-2013-204487\nPMC4392314\nSystemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status.\n To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc).\n The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed.\n Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset.\n These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.\n\n\n"
},
{
"text": "\n135176\nMedication use in pregnancy: a cross-sectional, multinational web-based study.\n\nLupattelli, A\n\nSpigset, O\n\nTwigg, MJ\n\nZagorodnikova, K\n\nMårdby, AC\n\nMoretti, ME\n\nDrozd, M\n\nPanchaud, A\n\nHämeen-Anttila, K\n\nRieutord, A\n\nGjergja Juraski, R\n\nOdalovic, M\n\nKennedy, D\n\nRudolf, G\n\nJuch, H\n\nPassier, A\n\nBjörnsdóttir, I\n\nNordeng, H\n\nBeiträge in Fachzeitschriften\nISI:000334459100076\n24534260.0\n10.1136/bmjopen-2013-004365\nPMC3927801\nIntercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use.\n Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire.\n Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia.\n Pregnant women and new mothers with children less than 1 year of age.\n Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use.\n The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants.\n In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.\n\nJuch, Herbert\n\n\n"
},
{
"text": "\n150358\nCancer patients' emotional distress, coping styles and perception of doctor-patient interaction in European cancer settings.\n\nMeggiolaro, E\n\nBerardi, MA\n\nAndritsch, E\n\nNanni, MG\n\nSirgo, A\n\nSamorì, E\n\nFarkas, C\n\nRuffilli, F\n\nCaruso, R\n\nBellé, M\n\nJuan Linares, E\n\nde Padova, S\n\nGrassi, L\n\nBeiträge in Fachzeitschriften\nISI:000381290300005\n26155817.0\n10.1017/S1478951515000760\nNone\nAs a part of a European study, we cross-culturally examined the rate of emotional distress and maladaptive coping and their association with cancer patients' satisfaction with their interactions with the physician responsible for their care.\n Cancer patients (n = 302) from one Middle European (Austria) and two Southern European (Italy, Spain) countries completed the NCCN Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation (AP) and Hopelessness (H) sub-scales, and the Physician Patient Satisfaction with Doctors Questionnaire (PSQ).\n The prevalence of emotional distress (DT caseness) was 60% (26.1% mild, 18.8% moderate, and 14.9% severe distress). Maladaptive coping (Mini-MAC cases) was found in 22.8% (hopeless cases), and 22.5% (anxious preoccupation cases). PSQ-MD was significantly correlated with Mini-MAC/H and Mini-Mac/AP, while PSQ-PS was negatively correlated with Mini-MAC/H. DT cases and those with higher levels of hopelessness reported higher scores on PSQ-MD and lower on PSQ-PS than non-cases. Some differences were found between countries both as far as patients' coping and perception of the interaction with doctors. In hierarchical multiple regression analysis, after adjusting for socio-demographic and medical variables, Mini-MAC/H significantly predicted the scores on PSQ-MD (positive direction) and PSQ-PS (negative direction).\n The study confirms that about one out of three cancer patients have moderate to high level of emotional distress and about one out of four, clinically significant maladaptive coping. Also, patients showing hopelessness and distress tended to perceive their doctors as both disengaged and less supportive. These results highlights the need for physicians to monitor their patient's level of distress and coping mechanisms and to adjust their own relational and communication style according to patients' psychological condition. Also, cross-cultural issues should be taken into account when exploring psychosocial variables and cancer patients' perception of and satisfaction with the interaction with their doctors.\n\nAndritsch, Elisabeth\n\nFarkas, Clemens\n\n\n"
},
{
"text": "\n155935\nDifferent impact of normo- and hypotensive brain death on renal macro- and microperfusion--an experimental evaluation in a porcine model.\n\nMehrabi, A\n\nGolling, M\n\nKörting, M\n\nHashemi, B\n\nAhmadi, R\n\nKashfi, A\n\nSchemmer, P\n\nGutt, CN\n\nPahlavan, PS\n\nSchmidt, J\n\nBüchler, MW\n\nKraus, TW\n\nBeiträge in Fachzeitschriften\nISI:000224354300005\n15292465.0\n10.1093/ndt/gfh424\nNone\nDespite the growing use of kidneys from living donors, organs harvested from brain dead donors are the dominant graft types used in renal transplantation. It is accepted that brain death (BD) has a damaging effect on the renal allograft, with a lower graft survival. Amongst various causes, changes in renal microperfusion could be responsible. Renocortical microperfusion was assessed during BD using thermal diffusion in a porcine model.\n Two types of BD were induced in two groups of pigs [hypotension (Hypo-BD): n = 11; normotension (Normo-BD): n = 10] and compared to controls (n = 5) over a period of 210 min. We analysed systemic parameters [heart rate (HR), mean arterial blood pressure (MAP)], aortic blood flow (ABF) and renal perfusion [renal artery blood flow (RABF) and renocortical blood flow (RCBF)].\n Following the two distinct forms of BD induction, a stable normo- or hypotension was observed. Haemodynamic parameters were only slightly changed (control group: MAP, 62+/-2 mmHg; HR, 95+/-3/min; Normo-BD: MAP, 56+/-4 mmHg; HR, 104+/-8/min; Hypo-BD: MAP, 43+/-3 mmHg; HR, 112+/-7/min). Solely dependent on systemic haemodynamics, RABF and RCBF decreased in the Hypo-BD (RABF: 142+/-19 to 94+/-9 ml/100 g/min; RCBF: 80+/-4 to 52+/-2 ml/100 g/min), while in Normo-BD group RABF mildly changed (158+/-13 ml/100 g/min) and RCBF decreased slightly from 76+/-3 to 70+/-6 ml/100 g/min. As opposed to the Normo-BD group, animals with Hypo-BD showed a significant decrease in RABF (reduction of 34%) and RCBF (reduction of 35%) with a sharp drop of MAP (reduction of 25%), however ABF remained relatively constant.\n In this model, a reduction of renocortical microperfusion in brain dead pigs was only found during haemodynamic instability (hypotension) and could not be attributed to BD as such. Our findings would support intensive cardiocirculatory stabilization for potential BD donors in order to minimize kidney preservation damage.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n156646\nResults of micronucleus assays with individuals who are occupationally and environmentally exposed to mercury, lead and cadmium.\n\nNersesyan, A\n\nKundi, M\n\nWaldherr, M\n\nSetayesh, T\n\nMišík, M\n\nWultsch, G\n\nFilipic, M\n\nMazzaron Barcelos, GR\n\nKnasmueller, S\n\nBeiträge in Fachzeitschriften\nISI:000390182300011\n27894681.0\n10.1016/j.mrrev.2016.04.002\nNone\nMillions of humans are exposed occupationally and environmentally to lead, mercury and cadmium compounds. Mercury compounds are less abundant but some of them belong to the most toxic chemicals which are known. We evaluated the literature to find out if these metals act in humans as genotoxic carcinogens and if their health effects can be predicted by use of micronucleus (MN) assays with lymphocytes and/or with other genotoxicity tests. Numerous studies showed that lead and mercury induce cancer in humans and also in animals, in vitro experiments with cultured cells indicate that they cause DNA damage via different molecular mechanisms including release of reactive oxygen species and interactions with DNA repair processes. Also in most human studies, positive results were obtained in MN tests with lymphocytes (all 15 occupational studies with lead yielded positive results, with mercury 6 out of 7 investigations were positive). For cadmium, there is clear evidence that it causes cancer in humans; however, induction of chromosomal damage was only seen in high dose experiments with mammalian cells while results of animal and human studies yielded conflicting results (only in 2 of 5MN trials with humans positive findings were reported). Possibly, non-genotoxic mechanisms such as inhibition of apoptosis and interaction with signaling pathways account for the carcinogenic properties of cadmium species. The findings of MN studies with lead and mercury are in excellent agreement with results which were obtained with other endpoints (e.g. chromosomal aberrations and comet formations) and it is evident that this approach can be used for occupational and environmental monitoring of exposed individuals. Important future tasks will be the realization of larger studies with a uniform standardized protocol, the additional evaluation of anomalies other than MN (nuclear buds and bridges) and the combination of such trials with investigations which allow to define the molecular mechanisms relevant for exposed humans.\n Copyright © 2016 Elsevier B.V. All rights reserved.\n\nWultsch, Georg\n\n\n"
},
{
"text": "\n169388\nEffects of a restrictive blood transfusion protocol on acute pediatric burn care: Transfusion threshold in pediatric burns.\n\nVoigt, CD\n\nHundeshagen, G\n\nMalagaris, I\n\nWatson, K\n\nObiarinze, RN\n\nHasanpour, H\n\nWoodson, LC\n\nCapek, KD\n\nLee, JO\n\nNunez Lopez, O\n\nCambiaso-Daniel, J\n\nBranski, LK\n\nNorbury, WB\n\nFinnerty, CC\n\nHerndon, DN\n\nBeiträge in Fachzeitschriften\nISI:000451388100004\n30252776.0\n10.1097/TA.0000000000002068\nPMC6280964\nBlood transfusion is costly and associated with various medical risks. Studies in critically ill adult and pediatric patients suggest that implementation of more restrictive transfusion protocols based on lower threshold hemoglobin concentrations can be medically and economically advantageous. The purpose of this study was to evaluate the implications of a hemoglobin threshold change in pediatric burn patients.\n We implemented a change in hemoglobin threshold from 10 g/dL to 7 g/dL and compared data from patients before and after this protocol change in a retrospective review. Primary endpoints were hemoglobin concentration at baseline, before transfusion, and after transfusion; amount of blood product administered; and mortality. Secondary endpoints were the incidence of sepsis based on the American Burn Association physiological criteria for sepsis and mean number of septic days per patient. All endpoint analyses were adjusted for relevant clinical covariates via generalized additive models or Cox proportional hazard model. Statistical significance was accepted at p less than 0.05.\n Patient characteristics and baseline hemoglobin concentrations (pre, 13.5 g/dL; post, 13.3 g/dL; p > 0.05) were comparable between groups. The group transfused based on the more restrictive hemoglobin threshold had lower hemoglobin concentrations before and after transfusion throughout acute hospitalization, received lower volumes of blood during operations (pre, 1012 mL; post, 824 mL; p < 0.001) and on days without surgical procedures (pre, 602 mL; post, 353 mL; p < 0.001), and had a lower mortality (pre, 8.0%; post, 3.9%; mortality hazard decline, 0.55 [45%]; p < 0.05). Both groups had a comparable incidence of physiological sepsis, though the more restrictive threshold group had a lower number of sepsis days per patient.\n More restrictive transfusion protocols are safe and efficacious in pediatric burn patients. The associated reduction of transfused blood may lessen medical risks of blood transfusion and lower economic burden.\n Therapeutic, level IV.\n\nBranski, Ludwik\n\nCambiaso Daniel, Janos\n\n\n"
},
{
"text": "\n174717\nDiurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study.\n\nFreynhofer, MK\n\nHein-Rothweiler, R\n\nHaller, PM\n\nAradi, D\n\nDézsi, DA\n\nGross, L\n\nOrban, M\n\nTrenk, D\n\nGeisler, T\n\nHuczek, Z\n\nToth-Gayor, GG\n\nMassberg, S\n\nHuber, K\n\nSibbing, D\n\nBeiträge in Fachzeitschriften\nISI:000463041700016\n30695790.0\n10.1055/s-0038-1677549\nNone\nLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2, 10 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2, 26 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1, 65) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5-10 a.m.). In prasugrel-treated patients (n = 1, 61), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.\n Georg Thieme Verlag KG Stuttgart · New York.\n\nToth-Gayor, Gabor\n\n\n"
},
{
"text": "\n175188\nEAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma.\n\nAgache, I\n\nLau, S\n\nAkdis, CA\n\nSmolinska, S\n\nBonini, M\n\nCavkaytar, O\n\nFlood, B\n\nGajdanowicz, P\n\nIzuhara, K\n\nKalayci, O\n\nMosges, R\n\nPalomares, O\n\nPapadopoulos, NG\n\nSokolowska, M\n\nAngier, E\n\nFernandez-Rivas, M\n\nPajno, G\n\nPfaar, O\n\nRoberts, GC\n\nRyan, D\n\nSturm, GJ\n\nvan Ree, R\n\nVarga, EM\n\nvan Wijk, RG\n\nYepes-Nuñez, JJ\n\nJutel, M\n\nBeiträge in Fachzeitschriften\nISI:000471283000001\n31095767.0\n10.1111/all.13749\nNone\nAllergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence-based recommendations for the use of house dust mites (HDM) AIT as add-on treatment for HDM-driven allergic asthma. This guideline was developed by a multi-disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT-tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add-on to regular asthma therapy for adults with controlled or partially controlled HDM-driven allergic asthma (conditional recommendation, moderate-quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM-driven allergic asthma as the add-on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low-quality evidence).\n © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nSturm, Gunter\n\nVarga, Eva-Maria\n\n\n"
},
{
"text": "\n178425\nBacteremia in Childhood Life-Threatening Infections in Urban Gambia: EUCLIDS in West Africa.\n\nSecka, F\n\nHerberg, JA\n\nSarr, I\n\nDarboe, S\n\nSey, G\n\nSaidykhan, M\n\nWathuo, M\n\nKaforou, M\n\nAntonio, M\n\nRoca, A\n\nZaman, SMA\n\nCebey-López, M\n\nBoeddha, NP\n\nPaulus, S\n\nKohlfürst, DS\n\nEmonts, M\n\nZenz, W\n\nCarrol, ED\n\nde Groot, R\n\nSchlapbach, L\n\nMartinon-Torres, F\n\nBojang, K\n\nLevin, M\n\nvan der Flier, M\n\nAnderson, ST\n\nBeiträge in Fachzeitschriften\nISI:000493121500018\n31660408.0\n10.1093/ofid/ofz332\nPMC6798247\nThe limited availability of microbiology services in sub-Saharan Africa impedes accurate diagnosis of bacterial pathogens and understanding of trends in prevalence and antibiotic sensitivities. We aimed to characterize bacteremia among hospitalized children in The Gambia and to identify factors associated with bacteremia and mortality.\n We prospectively studied children presenting with suspected severe infection to 2 urban hospitals in The Gambia, between January 2013 and September 2015. Demographic and anthropometric data, clinical features, management, and blood culture results were documented. Urine screens for antibiotic activity were performed in a subset of participants.\n Of 411 children enrolled (median age, 29 months; interquartile range, 11-82), 79.5% (325 of 409) reported prehospital antibiotic use. Antimicrobial activity by urinary screen for antibiotic activity was detected in 70.8% (n = 80 of 113). Sixty-six bacterial pathogens were identified in 65 (15.8%) participants and Staphylococcus aureus predominated. Gram-positive organisms were more commonly identified than Gram-negative (P < .01). Antibiotic resistance against first-line antimicrobials (ampicillin and gentamicin) was common among Gram-negative bacteria (39%; range, 25%-100%). Factors significantly associated with bacteremia included the following: gender, hydration status, musculoskeletal examination findings, admission to the Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine hospital, and meeting sepsis criteria. Those associated with increased mortality were presence of a comorbidity, clinical pallor, tachypnea, and altered consciousness. Tachycardia was associated with reduced mortality.\n The bacteremia rate in children with suspected childhood life-threatening infectious diseases in The Gambia is high. The pattern of pathogen prevalence and antimicrobial resistance has changed over time compared with previous studies illustrating the importance of robust bacterial surveillance programs in resource-limited settings.\n © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.\n\nKohlfürst, Daniela\n\nZenz, Werner\n\n\n"
}
]
}