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  • 1
    In: International Wound Journal, December 2011, Vol.8(6), pp.578-584
    Description: We analysed the effect of different body features on contact area, interface pressure and pressure distribution of three different mattresses. Thirty‐eight volunteers (age ranged from 17 to 73 years, 23 females) were asked to lie on three different mattresses in a random order: I, standard hospital foam mattresses; II, higher specification foam mattresses (Viscorelax Sure); III, constant low pressure devices (CareMedx, AirSystems). Measurements were performed in supine position and in a 90° left‐ and right‐sided position, respectively, using a full‐body mat (pressure mapping device Xsensor X2‐Modell). Outcome variables were contact area (CA) in cm, mean interface pressure (IP) in mmHg and pressure distribution (PD) estimated as rate of low pressures between 5 and 33 mmHg on each mattress in percent. Mean CA was lowest in the standard hospital foam mattresses and increased in the higher specification foam mattresses and was highest in the constant low pressure device (supine position: 491 ± 86 cm, 615 ± 95 cm, 685 ± 116 cm). Mean IP was highest in the standard hospital foam mattresses and lower but similar in the higher specification foam mattresses and the constant low pressure devices (supine position: 22·3 ± 1·5 mmHg, 17·6 ± 1·7 mmHg, 17·6 ± 2·2 mmHg). Models were estimated for CA, IP and PD including the independent variables height, weight and waist‐to‐hip‐ratio (WHR). They show that body morphology seems to play a minor role for CA, IP and PD, but very thin and tall patients and very small and obese people might benefit from different mattresses. Our data show that CA increases with increasing specification of mattresses. Higher specification foam mattresses and constant low pressure devices show similar IP, but constant low pressure devices show a wider pressure distribution. Body morphology should be considered to optimise prevention for single patients.
    Keywords: Interface Pressure ; Mattresses ; Pressure Ulcer ; Waist‐To‐Hip‐Ratio
    ISSN: 1742-4801
    E-ISSN: 1742-481X
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  • 2
    Language: English
    In: Clinical Research in Cardiology, 2013, Vol.102(8), pp.607-614
    Description: Byline: Undine Pittl (1), Alexandra Schratter (2), Steffen Desch (1), Raluca Diosteanu (1), Denise Lehmann (1), Katharina Demmin (1), Jacqueline Horig (3), Gerhard Schuler (1), Thorsten Klemm (4), Meinhard Mende (5), Holger Thiele (1) Keywords: Resuscitation; Cardiac arrest; Hypothermia; Neuron-specific enolase; Outcome; Cooling-associated complications Abstract: Introduction Mild induced hypothermia (MIH) is indicated for comatose survivors of sudden cardiac arrest (SCA) to improve clinical outcome. In this study, we compared the efficacy of two different cooling devices for temperature management in SCA survivors. Methods Between April 2008 and August 2009, 80 patients after survived in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) were included in this prospective, randomized, single center study. Hypothermia was induced after randomization by either invasive Coolgard.sup.(r) cooling or non-invasive ArcticSun.sup.(r) surface cooling at 33.0 degC core body temperature for 24 h followed by active rewarming. The primary endpoint was defined as the efficacy of both cooling systems, measured by neuron-specific enolase (NSE) levels as a surrogate parameter for brain damage. Secondary efficacy endpoints were the clinical and neurological outcome, time to start of cooling and reaching the target temperature, target temperature-maintenance and hypothermia-associated complications. Results NSE at 72 h did not differ significantly between the 2 groups with 16.5 ng/ml, interquartile range 11.8--46.5 in surface-cooled patients versus 19.0 ng/ml, interquartile range 11.0--42.0 in invasive-cooled patients, p = 0.99. Neurological and clinical outcome was similar in both groups. Target temperature of 33.0 degC was maintained more stable in the invasive group (33.0 versus 32.7 degC, p 〈 0.001). Bleeding complications were more frequent with invasive cooling (n = 17 [43.6 %] versus n = 7 [17.9 %] p = 0.03). Conclusion Invasive cooling has advantages with respect to temperature management over surface cooling however, did not result in different outcome as measured by NSE release in SCA survivors. Bleeding complications were more frequently encountered by invasive cooling. Author Affiliation: (1) Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Strumpellstr. 39, 04289, Leipzig, Germany (2) Hospital Hietzing, Vienna, Austria (3) Hospital Freudenstadt, Freudenstadt, Germany (4) MVZ Laboratory Dr. Reising-Ackermann and Colleagues, Leipzig, Germany (5) University of Leipzig, Coordination Centre for Clinical Trials, Leipzig, Germany Article History: Registration Date: 17/04/2013 Received Date: 09/03/2013 Accepted Date: 17/04/2013 Online Date: 05/05/2013 Article note: Trial registration: ClinicalTrials.gov NCT: 00843297.
    Keywords: Resuscitation ; Cardiac arrest ; Hypothermia ; Neuron-specific enolase ; Outcome ; Cooling-associated complications
    ISSN: 1861-0684
    E-ISSN: 1861-0692
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  • 3
    Language: English
    In: PLoS ONE, April 12, 2017, Vol.12(4), p.e0175563
    Description: VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes and PD-L1 tumoral and stromal expression in colorectal cancers harboring VEGFA amplification or chromosome 6 polysomy. 38 CRCs of which 13 harbored VEGFA amplification, 6 with Chr6 polysomy and 19 with neutral VEGFA copy number were assessed by immunohistochemistry for CD68 (marker for M1/M2 macrophages), CD163 (M2 macrophages), programmed death 1(PD-1)- tumor infiltrating and stromal lymphocytes as well as tumoral and stromal PD-1 ligand (PD-L1) expression. CRCs with VEGFA amplification or Chr6 polysomy were associated with decreased M1/M2 macrophages, reduced PD-1-expressing lymphocyte infiltration, as well as reduced stromal expression of PD-L1 at the tumor front. Compared to intermediate-grade CRCs, high-grade CRCs were associated with increased M1/M2 macrophages and increased tumoral expression of PD-L1. Our results suggest that VEGFA amplification or Chr6 polysomy is associated with an altered tumor immune microenvironment.
    Keywords: Tumors -- Genetic Aspects ; Colorectal Cancer -- Genetic Aspects ; Vascular Endothelial Growth Factor ; B Cells ; Immunohistochemistry ; Macrophages
    ISSN: 1932-6203
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  • 4
    In: PLoS ONE, 2017, Vol.12(4)
    Description: Aims In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. Material and methods Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). Results Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. Conclusion The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Research And Analysis Methods ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Clinical chemistry, November 2018, Vol.64(11), pp.1646-1656
    Description: Measurements of plasma or urinary metanephrines are recommended for diagnosis of pheochromocytoma and paraganglioma (PPGL). What test offers optimal diagnostic accuracy for patients at high and low risk of disease, whether urinary free metanephrines offer advantages over deconjugated metanephrines, and what advantages are offered by including methoxytyramine in panels all remain unclear. A population of 2056 patients with suspected PPGLs underwent prospective screening for disease using mass spectrometric-based measurements of plasma free, urinary deconjugated, and urinary free metanephrines and methoxytyramine. PPGLs were confirmed in 236 patients and were excluded in others on follow-up evaluation. Measurements of plasma free metabolites offered higher ( 〈 0.01) diagnostic sensitivity (97.9%) than urinary free (93.4%) and deconjugated (92.9%) metabolites at identical specificities for plasma and urinary free metabolites (94.2%) but at a lower ( 〈 0.005) specificity for deconjugated metabolites (92.1%). The addition of methoxytyramine offered little value for urinary panels but provided higher ( 〈 0.005) diagnostic performance for plasma measurements than either urinary panel according to areas under ROC curves (0.991 vs 0.972 and 0.964). Diagnostic performance of urinary and plasma tests was similar for patients at low risk of disease, whereas plasma measurements were superior to both urinary panels for high-risk patients. Diagnosis of PPGLs using plasma or urinary free metabolites provides advantages of fewer false-positive results compared with commonly measured deconjugated metabolites. The plasma panel offers better diagnostic performance than either urinary panel for patients at high risk of disease and, with appropriate preanalytics, provides the test of choice. Measurements of methoxytyramine in urine show limited diagnostic utility compared with plasma.
    Keywords: Metanephrine ; Adrenal Gland Neoplasms -- Diagnosis ; Chromaffin Cells -- Metabolism ; Dopamine -- Analogs & Derivatives ; Paraganglioma -- Diagnosis
    ISSN: 00099147
    E-ISSN: 1530-8561
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2016, Vol.205(5), pp.485-500
    Description: In cystic fibrosis (CF) patients’ airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators’ interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP-1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1β, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus’ virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected.
    Keywords: Cystic fibrosis ; Nasal lavage ; Inflammation ; Staphylococcus aureus
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Cardiovascular Revascularization Medicine, March 2016, Vol.17(2), pp.88-94
    Description: Obesity with its worldwide growing prevalence is an established cardiovascular risk factor with increased morbidity and mortality. However, the phenomenon, that mild to moderate obesity seems to represent a protective effect on diseases has been termed the “obesity paradox”. We retrospectively assessed 529 patients (72.6% male, mean age 59.7 ± 12.7 years) admitted with ST-elevation myocardial infarction (STEMI). The female and male study populations were separated into four body mass index (BMI) groups: ≤ 24.9 kg/m , 25.0–29.9 kg/m , 30.0–34.9 kg/m and ≥ 35.0 kg/m . Blood samples of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were analyzed. With increasing BMI group the rate of major adverse cardiac events (MACE) decreased in all patients (test for trend = 0.041). No gender difference between MACE and BMI could be noticed ( = 0.16). A higher risk for MACE was indicated in group BMI ≤ 18.5 kg/m in comparison to group BMI 25.0–29.9 kg/m (OR: 7.93; 95% CI: 1.75–35.89; = 0.0091), whereas group BMI 30.0–34.9 kg/m was significant associated with a lower risk in comparison to group BMI 25.0–29.9 kg/m (OR: 0.65; 95% CI: 0.21–1.96; = 0.044). An association between HDL-c ( = 0.55) or LDL-c ( = 0.10) and MACE could not be detected. The study demonstrates that patients with STEMI and a BMI of 30.0–34.9 kg/m have a decreased risk for MACE compared to patients with normal BMI. No gender related differences were indicated. An association between MACE and lipoproteins could not be detected.
    Keywords: Body Mass Index ; Major Adverse Cardiac Events ; Obesity ; St-Segment Elevation Myocardial Infarction ; Medicine
    ISSN: 1553-8389
    E-ISSN: 1878-0938
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  • 8
    Language: English
    In: BMC family practice, 26 April 2016, Vol.17, pp.49
    Description: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life, mortality and resulting costs. Despite extensive evidence of risk factors for adverse drug reactions, there are few prospective trial data about an individualized risk assessment including pharmacogenetic information to increase patient safety. By conducting a health economic analysis, we will evaluate if the application of an individualized drug therapy in daily routine is cost-effective. German Clinical Trials Register: DRKS00006256 , date of registration 09/01/15.
    Keywords: Adr Risk Assessment ; Adverse Drug Reaction ; Clinical Decision Support System ; Drug Interaction ; Elderly ; Individualized Medicine ; Pharmacogenetics ; Polymedication ; Decision Support Techniques ; Polypharmacy ; Clinical Decision-Making -- Methods ; Drug-Related Side Effects and Adverse Reactions -- Diagnosis
    E-ISSN: 1471-2296
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  • 9
    In: Liver Transplantation, January 2018, Vol.24(1), pp.15-25
    Description: Late allocation of organs for transplant impairs post–liver transplantation (LT) survival. Cardiac dysfunction, especially diastolic and autonomic dysfunction, is frequent and plays an important role in the prognosis of patients with cirrhosis. However, the role of myocardial contractility is unexplored, and its prognostic value is controversially discussed. This study analyses the role of myocardial contractility assessed by speckle tracking echocardiography in LT allocation. In total, 168 patients with cirrhosis (training cohort, 111; validation cohort [VC], 57) awaiting LT in 2 centers were included in this retrospective study. Also, 51 patients from the training and all patients from the VC were transplanted, 36 patients of the training and 38 of the VC were alive at the end of follow‐up, and 21 nontransplanted patients died. Contractility of the left ventricle (LV) increased with severity of the Child‐Pugh score. Interestingly, higher LV contractility in the training cohort patients, especially in those with Child‐Pugh C, was an independent predictor of reduced transplant‐free survival. In male patients, the effects on survival of increased left and right ventricular myocardial contractility were more pronounced. Notably, competing risk analysis demonstrated that increased contractility is associated with earlier LT, which could be confirmed in the VC. Importantly, LV myocardial contractility had no impact on survival of patients not receiving LT or on post‐LT survival. In conclusion, this study demonstrates for the first time that increased myocardial contractility in decompensated patients identifies patients who require LT earlier, but without increased post‐LT mortality. AASLD.
    Keywords: Liver Transplantation ; Myocardial Contraction ; Patient Selection ; End Stage Liver Disease -- Surgery ; Heart -- Physiopathology ; Liver Cirrhosis -- Surgery;
    ISSN: 1527-6465
    E-ISSN: 1527-6473
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  • 10
    In: Medicine & Science in Sports & Exercise, 1996, Vol.28(9), pp.1081-1086
    Description: This study compares hemodynamic, metabolic, and gas exchange responses, catecholamine levels, and symptoms in 35 male patients with chronic heart failure (CHF) ([mean ± SD] age 53 ± 11 yr; ejection fraction 24± 11%) during three differently graded exercise test protocols. On three consecutive days patients performed cycle ergometry supine, with prolonged steps (prol BE) and right heart catheterization, ramplike cycle ergometry sitting (ramp BE), and ramplike treadmill walking (TMW). As in routine clinical practice, the prol BE was terminated when pathologic central hemodynamics and/or increased symptomology occurred, and ramp BE and TMW due to increased symptomology and/or physician's decision. During prol BE at ventilatory threshold (VT) the ˙VO2 (8.6 ± 1.8 ml·kg·min) was lower than during ramp BE (9.3± 2.1 ml·kg·min) (P 〈 0.017) and TMW (11.8 ± 2.3 ml·kg·min)(P 〈 0.0001). Prol BE, ramp BE, and TMW also differed significantly with respect to ventilation (22 ± 71·min; 26 ± 6 l·min; 29 ± 7 l·min;P 〈 0.01) and heart rate (100 ± 15 beats·min; 103 ± 18 beats·min; 110± 16 beats·min; P 〈 0.017). No differences were found in lactate levels, catecholamine levels, and ratings of leg fatigue and dyspnea. At test termination, the peak ˙VO2 during prol BE(10.8 ± 3.3 ml·kg·min) was lower than during ramp BE (13.3 ± 4.1 ml·kg·min)(P 〈 0.0001) and TMW (14.7 ± 3.4 ml·kg·min) (P 〈 0.0001). Peak norepinephrine value during ramp BE (4.531 ± 2.788 nmol·l) was higher than during prol BE (3.707 ± 2.262 nmol·l) (P 〈 0.001). Among the three tests, no significant differences were found for peak values of heart rate, lactate, and ratings of dyspnea. Although the ˙VO2·kg at VT was significantly higher during ramp BE and TMW compared to prol BE (P〈 0.001), the values expressed as a percent of peak˙VO2·kg were significantly lower (70 ± 4%; 72 ± 6%; 79 ± 3%; P 〈 0.017). A systematic effect on aerobic capacity with reduced peak values during ramp BE and TMW was demonstrated when test termination was based primarily on pathological findings of central hemodynamics from prol BE.
    Keywords: Oxygen Consumption ; Exercise -- Physiology ; Exercise Test -- Methods ; Heart Failure -- Physiopathology;
    ISSN: 0195-9131
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