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1.
Scand J Gastroenterol ; 59(4): 512-517, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38149333

ABSTRACT

BACKGROUND/AIMS: While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. METHODS: We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. RESULTS: Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. CONCLUSION: In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.


Subject(s)
Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage , Humans , Retrospective Studies , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/therapy , Acute Disease , Lactic Acid
2.
Scand J Gastroenterol ; 58(9): 1064-1070, 2023.
Article in English | MEDLINE | ID: mdl-37029631

ABSTRACT

BACKGROUND: Upper gastrointestinal bleeding (UGIB) from malignancies is associated with a poor outcome. Only a small number of studies on gastrointestinal tumor bleeding have been published so far, focusing mainly on bleeding from gastric cancer. Since the information on patients with UGIB from esophageal cancer appears insufficient, this study aimed to present clinical and endoscopic findings, treatment options as well as clinical outcomes such as rebleeding and survival of those patients. METHODS: This retrospective analysis included all patients admitted with UGIB from esophageal cancer at our university hospital during a 10-year period. RESULTS: 45 patients were analyzed of whom 26 (57.8%) already had cancer stage IV at index bleeding. 22 (48.9%) patients presented with hemodynamic instability and 30 (66.7%) patients received blood transfusions. Active bleeding was present in 24 (53.3%) patients, of whom 20 (83.3%) received endoscopic therapy. Successful hemostasis was achieved in 18 (90%) of 20 patients with Argon plasma coagulation used most frequently (52.4%). Early and delayed rebleeding occurred in 5 (12.5%) and 11 (27.5%) of all inoperable patients, respectively. Intake of anticoagulation or anti-platelet drugs were risk factors for delayed rebleeding and the median overall survival after index bleeding was 1.2 months. CONCLUSION: UGIB from esophageal cancer occurred most frequently in advanced tumor stages and was associated with significant blood loss. Even though initial endoscopic therapy was effective, rebleeding occurred in a significant number of patients. Those taking anticoagulants or anti-platelet drugs should be closely monitored for rebleeding. The overall survival after index bleeding was poor.


Subject(s)
Esophageal Neoplasms , Gastrointestinal Neoplasms , Hemostasis, Endoscopic , Humans , Retrospective Studies , Neoplasm Recurrence, Local/therapy , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Esophageal Neoplasms/complications , Esophageal Neoplasms/therapy , Gastrointestinal Neoplasms/complications
3.
Minim Invasive Ther Allied Technol ; 32(6): 335-340, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37640056

ABSTRACT

BACKGROUND: The goal of the present study was to develop a convolutional neural network for the detection of bleedings in capsule endoscopy videos using realistic clinical data from one single-centre. METHODS: Capsule endoscopy videos from all 133 patients (79 male, 54 female; meanage = 53.73 years, SDage = 26.13) who underwent capsule endoscopy at our institution between January 2014 and August 2018 were screened for pathology. All videos were screened for pathology by two independent capsule experts and confirmed findings were checked again by a third capsule expert. From these videos, 125 pathological findings (individual episodes of bleeding spanning a total of 5696 images) and 103 non-pathological findings (sections of normal mucosal tissue without pathologies spanning a total of 7420 images) were used to develop and validate a neural network (Inception V3) using transfer learning. RESULTS: The overall accuracy of the model for the detection of bleedings was 90.6% [95%CI: 89.4%-91.7%], with a sensitivity of 89.4% [95%CI: 87.6%-91.2%] and a specificity of 91.7% [95%CI: 90.1%-93.2%]. CONCLUSION: Our results show that neural networks can detect bleedings in capsule endoscopy videos under realistic, clinical conditions with an accuracy of 90.6%, potentially reducing reading time per capsule and helping to improve diagnostic accuracy.


Subject(s)
Capsule Endoscopy , Humans , Male , Female , Middle Aged , Adult , Capsule Endoscopy/methods , Neural Networks, Computer , Gastrointestinal Hemorrhage/diagnostic imaging , Videotape Recording
4.
Dig Dis ; 40(6): 826-834, 2022.
Article in English | MEDLINE | ID: mdl-35073555

ABSTRACT

INTRODUCTION: Use of risk scores for early assessment of patients with upper gastrointestinal bleeding (UGIB) is recommended by various guidelines. We compared Cologne-WATCH (C-WATCH) score with Glasgow-Blatchford score (GBS), Rockall score (RS), and pre-endoscopic RS (p-RS). METHODS: Patients with UGIB between January and December 2017 were retrospectively analyzed for 30-day mortality and composite endpoints risk of complications and need for intervention using areas under the receiver-operating characteristics curve (AUROC). Subgroup analysis was conducted for patients with UGIB on admission and in-hospital UGIB. RESULTS: A total of 252 patients were identified (67.5% men, mean age 63.8 ± 14.9 years). In-hospital UGIB occurred in 49.6%. AUROCs for 30-day mortality, risk of complications, and need for intervention (not applicable to RS) were 0.684 (95% confidence interval [CI]: 0.606-0.763), 0.665 (95% CI: 0.594-0.735), and 0.694 (95% CI: 0.612-0.775) for C-WATCH score, 0.724 (95% CI: 0.653-0.796) and 0.751 (95% CI: 0.687-0.815) for RS, 0.652 (95% CI: 0.57-0.735), 0.653 (95% CI: 0.579-0.727), and 0.673 (95% CI: 0.602-0.745) for p-RS and 0.652 (95% CI: 0.572-0.732), 0.663 (95% CI: 0.592-0.734), and 0.752 (95% CI: 0.683-0.821) for GBS. RS outperformed pre-endoscopic scores in predicting risk of complications, while there were no significant differences between pre-endoscopic scores except GBS outperforming p-RS in predicting need for intervention. The subgroup analysis obtained similar results. Positive predictive values for patients with estimated low risk for all three endpoints (C-WATCH score ≤1, RS ≤2, p-RS <1, and GBS ≤1) were 89%, 69%, 78%, and 92%. CONCLUSION: C-WATCH score performed similar to the established pre-endoscopic risk scores in patients with UGIB regarding relevant patient-related endpoints with no significant differences between both the subgroups.


Subject(s)
Gastrointestinal Hemorrhage , Male , Humans , Middle Aged , Aged , Female , Retrospective Studies , Severity of Illness Index , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Area Under Curve , Risk Assessment/methods , ROC Curve , Prognosis
5.
Int J Mol Sci ; 23(10)2022 May 17.
Article in English | MEDLINE | ID: mdl-35628414

ABSTRACT

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.


Subject(s)
Forkhead Box Protein O1 , Insulin-Like Growth Factor I , Obesity, Maternal , Prenatal Exposure Delayed Effects , Proto-Oncogene Proteins c-akt , Animals , DNA Damage , Female , Forkhead Box Protein O1/metabolism , Inflammation/metabolism , Insulin-Like Growth Factor I/metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/metabolism , Obesity, Maternal/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Prenatal Exposure Delayed Effects/metabolism , Proteomics , Proto-Oncogene Proteins c-akt/metabolism
6.
Inverse Probl ; 36(12): 125014, 2020 Dec.
Article in English | MEDLINE | ID: mdl-34149144

ABSTRACT

We study variational regularisation methods for inverse problems with imperfect forward operators whose errors can be modelled by order intervals in a partial order of a Banach lattice. We carry out analysis with respect to existence and convex duality for general data fidelity terms and regularisation functionals. Both for a priori and a posteriori parameter choice rules, we obtain convergence rates of the regularised solutions in terms of Bregman distances. Our results apply to fidelity terms such as Wasserstein distances, φ-divergences, norms, as well as sums and infimal convolutions of those.

7.
Z Gastroenterol ; 57(12): 1476-1480, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31826278

ABSTRACT

AIM: We tried to identify a possible correlation between meteorological factors and the frequency of gastrointestinal bleeding (GIB). METHODS: We analyzed all endoscopic examinations performed because of suspected GIB from 2013 to 2016 at Jena University Hospital, Germany. Confirmed bleeding events were correlated with local meteorological data and meteorological season using multivariate analysis. RESULTS: Among a total of 35 522 examinations, we identified 5310 endoscopies performed for suspected GIB (61.5 % upper, 38.5 % lower endoscopies). In 35.5 %, GIB could be ascertained, gastroduodenal ulcers being the most frequent bleeding source. Of bleedings, 46.7 % merited an endoscopic intervention. Multivariate analysis did not show a correlation between meteorological factors and the total number of bleeding events. In subgroup analysis, lower ambient temperatures as well as pronounced changes in daily temperature were significantly associated with a higher rate of variceal hemorrhage (incidence rate ratio [IRR]: 0.961 for higher minimum temperature, p = 0.019; IRR: 1.119 per degree temperature change, p = 0.021), whereas ulcerative bleeding was associated with changes in air pressure (IRR: 1.031 per hPa, p = 0.010). CONCLUSIONS: Our study does not support the correlation of meteorological conditions with the frequency of GIB per se. However, we found a statistically significant increase of variceal bleeding episodes along with lower ambient temperatures and pronounced changes in daily temperature. Patients at risk for variceal hemorrhage should be advised to avoid exposure to low temperatures, whenever possible. Ulcerative bleeding was significantly associated with changes in air pressure.


Subject(s)
Endoscopy/methods , Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/etiology , Meteorological Concepts , Weather , Esophageal and Gastric Varices/epidemiology , Gastrointestinal Hemorrhage/epidemiology , Germany/epidemiology , Humans , Incidence , Retrospective Studies , Seasons , Sunlight , Temperature
8.
Ecology ; 99(2): 503, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29338085

ABSTRACT

The Century Experiment at the Russell Ranch Sustainable Agriculture Facility at the University of California, Davis provides long-term agroecological data from row crop systems in California's Central Valley starting in 1993. The Century Experiment was initially designed to study the effects of a gradient of water and nitrogen availability on soil properties and crop performance in ten different cropping systems to measure tradeoffs and synergies between agricultural productivity and sustainability. Currently systems include 11 different cropping systems-consisting of four different crops and a cover crop mixture-and one native grass system. This paper describes the long-term core data from the Century Experiment from 1993-2014, including crop yields and biomass, crop elemental contents, aerial-photo-based Normalized Difference Vegetation Index data, soil properties, weather, chemical constituents in irrigation water, winter weed populations, and operational data including fertilizer and pesticide application amounts and dates, planting dates, planting quantity and crop variety, and harvest dates. This data set represents the only known long-term set of data characterizing food production and sustainability in irrigated and rainfed Mediterranean annual cropping systems. There are no copyright restrictions associated with the use of this dataset.

9.
Methods ; 115: 91-99, 2017 02 15.
Article in English | MEDLINE | ID: mdl-28189773

ABSTRACT

In this paper we propose a workflow to detect and track mitotic cells in time-lapse microscopy image sequences. In order to avoid the requirement for cell lines expressing fluorescent markers and the associated phototoxicity, phase contrast microscopy is often preferred over fluorescence microscopy in live-cell imaging. However, common specific image characteristics complicate image processing and impede use of standard methods. Nevertheless, automated analysis is desirable due to manual analysis being subjective, biased and extremely time-consuming for large data sets. Here, we present the following workflow based on mathematical imaging methods. In the first step, mitosis detection is performed by means of the circular Hough transform. The obtained circular contour subsequently serves as an initialisation for the tracking algorithm based on variational methods. It is sub-divided into two parts: in order to determine the beginning of the whole mitosis cycle, a backwards tracking procedure is performed. After that, the cell is tracked forwards in time until the end of mitosis. As a result, the average of mitosis duration and ratios of different cell fates (cell death, no division, division into two or more daughter cells) can be measured and statistics on cell morphologies can be obtained. All of the tools are featured in the user-friendly MATLAB®Graphical User Interface MitosisAnalyser.


Subject(s)
Cell Tracking/methods , Epithelial Cells/ultrastructure , Image Processing, Computer-Assisted/methods , Insulin-Secreting Cells/ultrastructure , Microscopy, Phase-Contrast/methods , Mitosis , Algorithms , Cell Line, Tumor , Cell Tracking/statistics & numerical data , HeLa Cells , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Microscopy, Fluorescence/instrumentation , Microscopy, Fluorescence/methods , Microscopy, Phase-Contrast/instrumentation , Time-Lapse Imaging/instrumentation , Time-Lapse Imaging/methods , Workflow
10.
J Environ Qual ; 46(5): 1123-1130, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28991971

ABSTRACT

Synthetic nitrogen (N) fertilizer formulations vary in their effects as substrates on nitrous oxide (NO) emissions. Mitigation of NO emissions can potentially be achieved through appropriate choice of N fertilizer sources combined with stabilizers. The effects of three N fertilizers and urease and nitrification inhibitors on NO emissions, crop N uptake, and yields were determined in a furrow-irrigated corn ( L.) system in Reiff loam soil in the Sacramento Valley of California for one growing season. Aqua ammonia (Aq. NH), urea ammonium nitrate (UAN), and calcium nitrate were sidedressed at the rate of 202 kg N ha. The control treatment received only starter fertilizer (20 kg N ha). Total seasonal emissions were in the order Aq. NH > UAN > calcium nitrate = control with 1.38, 0.97, 0.35, and 0.27 kg NO-N ha, respectively. A novel, positively charged form of dicyandiamide, KAS-771G77 (G77), was combined with Aq. NH and UAN to test the effectiveness of this nitrification inhibitor in reducing NO emissions. When combined with Aq. NH, G77 did not reduce the emissions, but G77 significantly lowered them in the UAN treatment. A similar reduction of NO emissions in the UAN treatment was achieved with the urease and nitrification inhibitor AgrotainPlus. Yields and N use efficiency did not differ among the fertilized treatments. Ammoniacal fertilizers had higher NO emissions than nitrate-based fertilizers, which could imply nitrification pathways as a source of NO emissions. The use of G77 or AgrotainPlus, when applied with UAN, was an effective NO mitigation practice.


Subject(s)
Fertilizers , Nitrous Oxide/analysis , Zea mays , Agricultural Irrigation , California , Guanidines , Nitrogen , Soil
11.
Proc Natl Acad Sci U S A ; 110(16): 6328-33, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23576736

ABSTRACT

The continuous increase of nitrous oxide (N2O) abundance in the atmosphere is a global concern. Multiple pathways of N2O production occur in soil, but their significance and dependence on oxygen (O2) availability and nitrogen (N) fertilizer source are poorly understood. We examined N2O and nitric oxide (NO) production under 21%, 3%, 1%, 0.5%, and 0% (vol/vol) O2 concentrations following urea or ammonium sulfate [(NH4)2SO4] additions in loam, clay loam, and sandy loam soils that also contained ample nitrate. The contribution of the ammonia (NH3) oxidation pathways (nitrifier nitrification, nitrifier denitrification, and nitrification-coupled denitrification) and heterotrophic denitrification (HD) to N2O production was determined in 36-h incubations in microcosms by (15)N-(18)O isotope and NH3 oxidation inhibition (by 0.01% acetylene) methods. Nitrous oxide and NO production via NH3 oxidation pathways increased as O2 concentrations decreased from 21% to 0.5%. At low (0.5% and 3%) O2 concentrations, nitrifier denitrification contributed between 34% and 66%, and HD between 34% and 50% of total N2O production. Heterotrophic denitrification was responsible for all N2O production at 0% O2. Nitrifier denitrification was the main source of N2O production from ammonical fertilizer under low O2 concentrations with urea producing more N2O than (NH4)2SO4 additions. These findings challenge established thought attributing N2O emissions from soils with high water content to HD due to presumably low O2 availability. Our results imply that management practices that increase soil aeration, e.g., reducing compaction and enhancing soil structure, together with careful selection of fertilizer sources and/or nitrification inhibitors, could decrease N2O production in agricultural soils.


Subject(s)
Air Pollution/analysis , Atmosphere/analysis , Nitric Oxide/metabolism , Nitrous Oxide/metabolism , Oxygen/metabolism , Soil/analysis , Air Pollution/prevention & control , Ammonium Sulfate , Analysis of Variance , Chromatography, Gas , Colorimetry , Denitrification/physiology , Nitrification/physiology , Oxidation-Reduction , Oxygen/analysis , Urea
12.
J Sci Food Agric ; 96(4): 1275-83, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-25885969

ABSTRACT

BACKGROUND: Soil organic carbon (SOC) is fundamental for mitigating climate change as well as improving soil fertility. Databases of SOC obtained from soil surveys in 1981 and 2011 were used to assess SOC change (0-20 cm) in croplands of Heilongjiang Province in northeast China. Three counties (Lindian, Hailun and Baoqing) were selected as typical croplands representing major soil types and land use types in the region. RESULTS: The changes in SOC density (SOCD) between 1981 and 2001 were -6.6, -14.7 and 5.7 Mg C ha(-1) in Lindian, Hailun and Baoqing Counties respectively. The total SOC storage (SOCS) changes were estimated to be -11.3, -19.1 and 16.5% of those in 1981 in the respective counties. The results showed 22-550% increases in SOCS in rice (Oryza sativa L.) paddies in the three counties, but 28-33% decreases in dry cropland in Lindian and Hailun Counties. In addition, an increase of 11.4 Mg C ha(-1) in SOCD was observed in state-owned farms (P < 0.05), whereas no significant change was observed in family-owned farms. CONCLUSION: Soil C:N ratio and initial SOCD related to soil groups were important determinants of SOCD changes. Land use and residue returning greatly affected SOC changes in the study region. To increase the topsoil SOCD, the results suggest the conversion of dry croplands to rice paddies and returning of crop residue to soils.


Subject(s)
Carbon/analysis , Crops, Agricultural/growth & development , Soil/chemistry , Agriculture/methods , China , Climate Change , Environmental Monitoring , Nitrogen/analysis , Oryza/growth & development , Glycine max/growth & development , Zea mays/growth & development
15.
BMJ Open Gastroenterol ; 11(1)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38458629

ABSTRACT

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.


Subject(s)
Hemostatics , Learning Curve , Humans , Aged , Retrospective Studies , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/surgery , Endoscopy, Gastrointestinal
16.
Lancet Haematol ; 11(3): e196-e205, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38301670

ABSTRACT

BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL. METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete. FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications. INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials. FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukopenia , Lymphoma, Large B-Cell, Diffuse , Humans , Female , Male , Aged , Prospective Studies , Rituximab , Lymphoma, Large B-Cell, Diffuse/drug therapy
17.
Biol Reprod ; 89(3): 59, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23843239

ABSTRACT

Uropathogenic Escherichia coli (UPEC)-associated epididymitis is commonly diagnosed in outpatient settings. Although the infection can be successfully cleared using antimicrobial medications, 40% of patients unexplainably show persistent impaired semen parameters even after treatment. Our aim was to investigate whether pathogenic UPEC and its associated virulence factor hemolysin (hlyA) perturb the structural and functional integrity of both the epididymis and sperm, actions that may be responsible for the observed impairment and possibly a reduction of fertilization capabilities. Semen collected from patients diagnosed with E. coli-only related epididymitis showed that sperm counts were low 14 days postantimicrobial treatment regardless of hlyA status. At Day 84 following treatment, hlyA production correlated with approximately 4-fold lower sperm concentrations than in men with hlyA-negative strains. In vivo experiments with the hlyA-producing UPEC CFT073 strain in a murine epididymitis model showed that just 3 days postinfection, structural damage to the epididymis (epithelial damage, leukocyte infiltration, and edema formation) was present. This was more severe in UPEC CFT073 compared to nonpathogenic E. coli (NPEC 470) infection. Moreover, pathogenic UPEC strains prematurely activated the acrosome in vivo and in vitro. Raman microspectroscopy revealed that UPEC CFT073 undermined sperm integrity by inducing nuclear DNA damage. Consistent with these observations, the in vitro fertilization capability of hlyA-treated mouse sperm was completely abolished, although sperm were motile. These findings provide new insights into understanding the possible processes underlying clinical manifestations of acute epididymitis.


Subject(s)
Epididymitis/microbiology , Epididymitis/pathology , Escherichia coli Infections/pathology , Spermatozoa/microbiology , Spermatozoa/ultrastructure , Urinary Tract Infections/pathology , Uropathogenic Escherichia coli/pathogenicity , Adult , Animals , Embryo, Mammalian/microbiology , Female , Humans , Infertility, Male/microbiology , Infertility, Male/pathology , Male , Mice , Mice, Inbred C57BL , Middle Aged , Semen Analysis , Young Adult
18.
Cell Tissue Res ; 354(2): 623-32, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23873629

ABSTRACT

TCam-2 cells are the main in vitro model for investigations into seminomatous tumors. However, despite their widespread use, questions remain regarding the cells' homogeneity and consequently how representative they are of seminomas. We assess the TCam-2 cell line using routine and novel authentication methods to determine its homogeneity, identify any cellular sub-populations and resolve whether any changes could be due to generational differentiation. TCam-2, embryonal carcinoma cells (2102EP) and breast cancer cell (MCF7) lines were assessed using qRT-PCR, immunocytochemistry, flow cytometry and short tandem repeat analyses. Raman maps of individual cells (minimum of 10) and single scan spectra from 200 cells per culture were obtained. TCam-2s displayed the characteristic marker gene expression pattern for seminoma, were uniform in size and granularity and short tandem repeat analysis showed no contamination. However, based only on physical parameters, flowcytometry was unable to differentiate between TCam-2 and 2102EPs. Raman maps of TCam-2s comprised three equally distributed, distinct spectral patterns displaying large intercellular single spectral variation. All other cells showed little variation. Principal component, cluster and local spectral angle analyses indicated that the TCam-2s contained two different types of cells, one of which comprised two subgroups and was similar to some 2102EP cells. Protein expression corroborated the presence of different cells and generational differences. The detailed characterization provided by the Raman spectra, augmented by the routine methods, provide substantiation to the long-held suspicion that TCam-2 are not homogeneous but comprise differing cell populations, one of which may be embryonal carcinoma in origin.


Subject(s)
Seminoma/diagnosis , Spectrum Analysis, Raman/methods , Testicular Neoplasms/diagnosis , Breast Neoplasms/chemistry , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Male , Seminoma/chemistry , Seminoma/pathology , Testicular Neoplasms/chemistry , Testicular Neoplasms/pathology
19.
Physica D ; 260(100): 145-158, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-24926113

ABSTRACT

We introduce two models of biological aggregation, based on randomly moving particles with individual stochasticity depending on the perceived average population density in their neighborhood. In the first-order model the location of each individual is subject to a density-dependent random walk, while in the second-order model the density-dependent random walk acts on the velocity variable, together with a density-dependent damping term. The main novelty of our models is that we do not assume any explicit aggregative force acting on the individuals; instead, aggregation is obtained exclusively by reducing the individual stochasticity in response to higher perceived density. We formally derive the corresponding mean-field limits, leading to nonlocal degenerate diffusions. Then, we carry out the mathematical analysis of the first-order model, in particular, we prove the existence of weak solutions and show that it allows for measure-valued steady states. We also perform linear stability analysis and identify conditions for pattern formation. Moreover, we discuss the role of the nonlocality for well-posedness of the first-order model. Finally, we present results of numerical simulations for both the first- and second-order model on the individual-based and continuum levels of description.

20.
Annu Rev Plant Biol ; 59: 341-63, 2008.
Article in English | MEDLINE | ID: mdl-18444903

ABSTRACT

This review considers some of the mechanistic processes that involve roots in the soil nitrogen (N) cycle, and their implications for the ecological functions that retain N within ecosystems: 1) root signaling pathways for N transport systems, and feedback inhibition, especially for NO(3)(-) uptake; 2) dependence on the mycorrhizal and Rhizobium/legume symbioses and their tradeoffs for N acquisition; 3) soil factors that influence the supply of NH(4)(+) and NO(3)(-) to roots and soil microbes; and 4) rhizosphere processes that increase N cycling and retention, such as priming effects and interactions with the soil food web. By integrating information on these plant-microbe-soil N processes across scales and disciplinary boundaries, we propose ideas for better manipulating ecological functions and processes by which the environment provides for human needs, i.e., ecosystem services. Emphasis is placed on agricultural systems, effects of N deposition in natural ecosystems, and ecosystem responses to elevated CO(2) concentrations. This shows the need for multiscale approaches to increase human dependence on a biologically based N supply.


Subject(s)
Ecosystem , Nitrogen/metabolism , Plant Roots/metabolism , Air , Biological Transport , Carbon Dioxide/metabolism , Fertilizers , Plant Development , Plant Roots/physiology , Rhizome/physiology , Soil
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