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1.
Effects of a single aerobic exercise on perfused boundary region and microvascular perfusion: a field study.
Fuchs, A, Neumann, T, Drinhaus, H, Herrmann, A, Vink, H, Annecke, T
Journal of clinical monitoring and computing. 2022;(2):371-377
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Abstract
The endothelium and the glycocalyx play a pivotal role in regulating microvascular function and perfusion in health and critical illness. It is unknown today, whether aerobic exercise immediately affects dimensions of the endothelial surface layer (ESL) in relation to microvascular perfusion as a physiologic adaption to increased nutritional demands. This monocentric observational study was designed to determine real-time ESL and perfusion measurements of the sublingual microcirculation using sidestream dark field imaging performed in 14 healthy subjects before and after completing a 10 km trial running distance. A novel image acquisition and analysis software automatically analysed the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration of the ESL, in vessels between 5 and 25 µm diameter. Microvascular perfusion was assessed by calculating RBC filling percentage. There was no significant immediate effect of exercise on PBR and RBC filling percentage. Linear regression analysis revealed a distinct association between change of PBR and change of RBC filling percentage (regression coefficient β: - 0.026; 95% confidence interval - 0.043 to - 0.009; p = 0.006). A single aerobic exercise did not induce a change of PBR or RBC filling percentage. The endothelium of the microvasculature facilitates efficient perfusion in vessels reacting with an increased endothelial surface layer.
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Can Isoflavones Influence Prostate Specific Antigen Serum Levels in Localized Prostate Cancer? A Systematic Review.
Ratha, P, Neumann, T, Schmidt, CA, Schneidewind, L
Nutrition and cancer. 2021;(3):361-368
Abstract
Low risk prostate cancer does not always necessitate aggressive or invasive intervention and is best monitored through active surveillance, but in daily practice a majority of men seek a more proactive approach. Therefore, tertiary chemoprevention is an attractive option for men seeking a way to slow disease progression. Several natural anti-carcinogens have been identified in soy beans, especially isoflavones. Case series have been published, demonstrating a positive influence of isoflavones on PSA serum levels in prostate cancer. Consequently, we decided to perform a systematic review about the effect of isoflavones compared to placebo on PSA levels in localized prostate cancer following the recommendations provided in the Cochrane Handbook of systematic Reviews. On the whole, the primary aim of this review is to summarize the evidence for the use of isoflavones in localized prostate cancer in terms of PSA response. As a result, in all randomized controlled trials identified for this review, isoflavones seem to have no influence on PSA levels in localized prostate cancer. The influence of isoflavones on overall survival in localized prostate cancer remains unclear. Furthermore, isoflavones are interesting substances for further research, for example in lipid metabolism and cholesterol.
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Allogeneic stem cell transplantation for mantle cell lymphoma-update of the prospective trials of the East German Study Group Hematology/Oncology (OSHO#60 and #74).
Krüger, WH, Hirt, C, Basara, N, Sayer, HG, Behre, G, Fischer, T, Grobe, N, Maschmeyer, G, Neumann, T, Schneidewind, L, et al
Annals of hematology. 2021;(6):1569-1577
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Abstract
Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma with an often aggressive course, incurable by chemotherapy. Consolidation with high-dose therapy and autologous stem cell transplantation (autoSCT) has a low transplant-related mortality but does not lead to a survival plateau. Allogeneic stem cell transplantation (alloSCT) is associated with a higher early mortality, but can cure MCL. To investigate alloSCT for therapy of MCL, we conducted two prospective trials for de novo MCL (OSHO#74) and for relapsed or refractory MCL (OSHO#60). Fifteen and 24 patients were recruited, respectively. Induction was mainly R-DHAP alternating with R-CHOP. Conditioning was either Busulfan/Cyclophosphamide or Treosulfan/Fludarabin. Either HLA-identical siblings or matched-unrelated donors with not more than one mismatch were allowed. ATG was mandatory in mismatched or unrelated transplantation. Progression-free survival (PFS) was 62% and overall survival (OS) was 68% after 16.5-year follow-up. Significant differences in PFS and OS between both trials were not observed. Patients below 56 years and patients after myeloablative conditioning had a better outcome compared to patients of the corresponding groups. Nine patients have died between day +8 and 5.9 years after SCT. Data from 7 long-term surviving patients showed an excellent Quality-of-life (QoL) after alloSCT. AlloSCT for MCL delivers excellent long-term survival data. The early mortality is higher than after autoSCT; however, the survival curves after alloSCT indicate the curative potential of this therapy. AlloSCT is a standard of care for all feasible patients with refractory or relapsed MCL and should offer to selected patients with de novo MCL and a poor risk profile. For defining the position of alloSCT in the therapeutic algorithm of MCL therapy, a randomized comparison of autoSCT and alloSCT is mandatory.
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Perioperative Management of Alcohol Withdrawal Syndrome.
Ungur, AL, Neumann, T, Borchers, F, Spies, C
Visceral medicine. 2020;(3):160-166
Abstract
BACKGROUND In the perioperative course, alcohol withdrawal syndrome (AWS) can occur in any setting, especially in aero-digestive and acute trauma surgery. Challenging issues are the overlap of other forms of delirium in perioperative and intensive care settings as well as general anesthesia masking the onset of withdrawal symptoms. In contrast to other etiologies of delirium, the pathophysiology and thus treatment strategy of AWS is different: the key point is the tolerance to GABAergic molecules of alcohol-dependent subjects resulting in central nervous hyperactivity once the effect of alcohol or other GABA-stimulating agents is decreased. SUMMARY Despite limitations due to insufficient accuracy of self-reporting questionnaires and limited feasibility in emergency settings, the AUDIT and the shortened AUDIT-C are the standard tools for detection of alcohol use disorders (AUD), as well as predicting AWS risk and severity in approximately half of these AUD patients. The most important risk factors for AWS are a high blood alcohol concentration at hospital admission, AWS episodes in medical history, and lack of control of alcohol use. Patients considered at risk for severe AWS must be treated with prophylactic medication before the onset of symptoms. Thiamine supplementation is required for all malnourished alcohol-dependent patients. Writing down alcohol-related diagnoses in the medical records requires the patient's presumed consent after shared decision-making. These reports should remain strictly confidential if the patient desires. Psychological support for the perioperative period as well as the following course should be offered to all AUD patients including support in short- and long-term detoxification. Alternative diagnoses must be ruled out with no timely delay, especially if fever and coma are the leading symptoms. The backbone of AWS therapy is the symptom-triggered administration of intravenous benzodiazepines (BZO) in escalating doses until the aimed revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) or Richmond Agitation-Sedation Scale (RASS) score is achieved. Clonidine, dexmedetomidine, baclofen, ketamine, and neuroleptics may be used as symptom-orientated adjuncts. The therapeutic administration of ethanol or clomethiazole is considered to be harmful in critically ill patients after the onset of AWS. General supportive and intensive care including high-dose thiamine supplementation are mandatory in severe AWS cases. The timely differential diagnosis of delirium is important - and AWS is a diagnosis of exclusion - because BZO are strongly recommended for AWS patients but may not be the treatment of choice in other etiologies of delirium. KEY MESSAGES Screening for AWS risk factors should be integrated in the preoperative and emergency assessment. Other severe diagnoses must be ruled out before the diagnosis of AWS can be established. Preventive treatment should be given to high-risk patients scoring positive for AUD and for patients with a lack of alcohol use control. The principles of AWS therapy are symptom-orientated doses of BZO and as adjuncts α2-agonists, neuroleptics, and others guided by repeated reassessment with validated tools and thiamine administration. Length of stay and morbidity are reduced if AWS therapy is symptom-orientated and protocol-based.
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Effects of Periodic Fasting on Fatty Liver Index-A Prospective Observational Study.
Drinda, S, Grundler, F, Neumann, T, Lehmann, T, Steckhan, N, Michalsen, A, Wilhelmi de Toledo, F
Nutrients. 2019;11(11)
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Plain language summary
Non-alcoholic fatty liver disease (NAFLD) comprises a number of liver disorders and is thought to have a prevalence of 20% in industrialised countries. NAFLD has been associated with dietary excess of saturated fatty acids, refined carbohydrates, and fructose. This prospective observational study evaluated the effects of periodic fasting on the fatty liver index (FLI), a combination of waist circumference, body mass index (BMI) and biochemical characteristics, which has been shown to closely correlate to magnetic resonance imaging (MRI) results, the gold standard for NAFLD diagnosis. 697 subjects fasted for 6-38 days (mean 8.5 days) in a clinical setting, whilst also engaging in an exercise programme, mindfulness and relaxation. Study subjects included both non-diabetics and type 2 diabetics. There were significant decreases in FLI, weight, BMI and waist circumference, as well as improvements in a number of metabolic blood parameters, in both diabetics and non-diabetics. There were no serious side effects and the intervention was well tolerated. The authors conclude that periodic fasting is an easily realisable, well-tolerated, non-pharmaceutical intervention, which effectively reduces the FLI.
Abstract
This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6-38). FLI decreased significantly (-14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (-19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by -1.51 ± 0.82 kg/m2, and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = -0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.
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Coupling Langmuir with Michaelis-Menten-A practical alternative to estimate Se content in rice?
Nothstein, AK, Eiche, E, Riemann, M, Nick, P, Maier, P, Tenspolde, A, Neumann, T
PloS one. 2019;(4):e0214219
Abstract
Selenium plays an important, but vastly neglected role in human nutrition with a narrow gap between dietary deficiency and toxicity. For a potential biofortification of food with Se, as well as for toxicity-risk assessment in sites contaminated by Se, modelling of local and global Se cycling is essential. As bioavailability of Se for rice plants depends on the speciation of Se and the resulting interactions with mineral surfaces as well as the interaction with Se uptake mechanisms in plants, resulting plant Se content is complex to model. Unfortunately, simple experimental models to estimate Se uptake into plants from substrates have been lacking. Therefore, a mass balance of Se transfer between lithosphere (represented by kaolinite), hydrosphere (represented by a controlled nutrient solution), and biosphere (represented by rice plants) has been established. In a controlled, closed, lab-scale system, rice plants were grown hydroponically in nutrient solution supplemented with 0-10 000 μg L-1 Se of either selenate or selenite. Furthermore, in a series of batch experiments, adsorption and desorption were studied for selenate and selenite in competition with each of the major nutrient oxy-anions, nitrate, sulfate and phosphate. In a third step, the hydroponical plants experiments were coupled with sorption experiments to study synergy effects. These data were used to develop a mass balance fitting model of Se uptake and partitioning. Adsorption was well-described by Langmuir isotherms, despite competing anions, however, a certain percentage of Se always remained bio-unavailable to the plant. Uptake of selenate or selenite by transporters into the rice plant was fitted with the non-time differentiated Michaelis-Menten equation. Subsequent sequestration of Se to the shoot was better described using a substrate-inhibited variation of the Michaelis-Menten equation. These fitted parameters were then integrated into a mass balance model of Se transfer.
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AGE-RAGE Interaction Does Not Explain the Clinical Improvements after Therapeutic Fasting in Osteoarthritis.
Drinda, S, Franke, S, Schmidt, S, Stoy, K, Lehmann, T, Wolf, G, Neumann, T
Complementary medicine research. 2018;(3):167-172
Abstract
BACKGROUND Therapeutic fasting improves joint pain in patients with osteoarthritis (OA), but the underlying mechanisms are unknown. Interactions of advanced glycation end products (AGEs) and their receptors (RAGE) play a role in OA pathogenesis. This study aimed to investigate whether the benefits of fasting in OA can be explained by changes in AGEs or RAGE. PATIENTS AND METHODS 37 patients with OA underwent fasting for 8 days. Serum levels of an AGE (N-ε-(carboxymethyl)-lysine; CML) and the soluble RAGE (sRAGE) as well as clinical outcome parameters such pain characteristics (measured by visual analogue scale; VAS), joint function (determined by the Western Ontario and McMaster Universities Arthritis Index; WOMAC), and quality of life (via the 36-Item Short-Form Health Survey (SF-36) questionnaire) were assessed. The variables were measured at baseline, the end of fasting, and at follow-up at 4 weeks. RESULTS The CML levels did not significantly change from baseline to the end of intervention (Δ = -25.6 ± 92.2 ng/ml; p = 0.10). In contrast, the sRAGE levels (Δ = -182.7 ± 171.4 ng/ml; p < 0.0001) and the sRAGE/CML ratio (Δ = -0.4 ± 0.6; p < 0.001) significantly decreased, but they returned to baseline levels 4 weeks after the end of fasting. The scores for pain, WOMAC, and the physical subscale of the SF-36 significantly improved during fasting. There was no correlation between the clinical outcomes and changes in serum levels of CML, sRAGE, or the sRAGE/CML ratio. CONCLUSIONS Fasting resulted in a significant but non-sustained reduction of sRAGE levels and the sRAGE/CML ratio in OA, while the CML levels did not change. Improvement in clinical endpoints of OA does not correlate with changes in CML or sRAGE.
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Therapy with renin-angiotensin system blockers after pulmonary vein isolation in patients with atrial fibrillation: who is a responder?
Berkowitsch, A, Neumann, T, Kuniss, M, Janin, S, Wojcik, M, Zaltsberg, S, Mitrovic, V, Pitschner, HF
Pacing and clinical electrophysiology : PACE. 2010;(9):1101-11
Abstract
AIMS: The data on anti-arrhythmic effect of renin-angiotensin-aldesteron system blockers (RASB) in patients with atrial fibrillation (AF) are controversially discussed. The goal of this analysis was to identify cohort of patients with AF and hypertension, who may have benefit from RASB therapy after pulmonary vein isolation (PVI). METHODS A total of 284 patients with AF and hypertension (paroxysmal AF [PAF]= 218, male = 185, age = 61 years, left ventricular ejection fraction = 60%, coronary artery disease = 42) considered for PVI were included. The patients with PAF were stratified according to time spent in AF (AF burden) within 3 months prior to admission (> 500 hours). Further patients were divided into two groups: (1) low-burden AF; (2) high-burden AF (PAF and persistent AF). In 195 patients, RASB therapy was administered. A 7-day continuous Holter electrocardiogram was performed after discharge, every 3 months thereafter and by symptoms. RESULTS Preventive effect of RASB was revealed in whole group (112 out of 195 [57%] vs 36 out of 89 [40%]; P = 0.025) and was more pronounced in patients with low-burden AF (79 out of 112 [71%] receiving RASB vs 27 out of 55 [49%] being on other drugs; P = 0.013). However, efficiency of RASB failed in patients with high-burden AF (33 out of 83 on RASB [40%] vs nine out of 34 on other drugs [27%]; P = 0.328). CONCLUSIONS Our data suggest that RASB appears to protect against AF recurrences after PVI in patients with low-burden paroxysmal AF. These results should be tested in a prospective study.
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9.
[Atherosclerosis in HIV-positive patients].
Neumann, T, Miller, M, Esser, S, Gerken, G, Erbel, R
Zeitschrift fur Kardiologie. 2002;(11):879-88
Abstract
Worldwide, human immunodeficiency virus (HIV) infection is one of the main health subjects. Even, the human immunodeficiency virus primarily effects the immune system, HIV infection also has an impact on other organs. Cardiovascular manifestations in HIV-infected patients could occur by the HI-virus itself or by opportunistic infections. Reports of myocardial infarction in young HIV-infected patients, who received protease inhibitors, have raised concerns about premature arteriosclerosis and coronary artery disease in this population. In the pre-protease inhibitor era, autopsy reports were the first to describe an association between coronary artery disease and HIV infection. Long-term antiretroviral therapy, including protease inhibitors, significantly reduced mortality, morbidity and revolutionized the care of HIV-infected patients. However, class-specific metabolic side effects, such as elevated total cholesterol and triglyceride levels and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy impair the cardiovascular risk profile of HIV-infected patients. Even epidemiological studies found no significant effect of antiretroviral treatment type on coronary heart disease or myocardial infarction, an increase of arteriosclerosis in HIV-infected patients is suspected. Recent results of autopsy studies and analyses of endothelial function in patients with HIV infection described an effect of HIV and antiretroviral therapy on premature arteriosclerosis. The present article gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.