Publications by authors named "Thomas Schroeder"

134 Publications

Association of scooter-related injury and hospitalization with electronic scooter sharing systems in the United States.

Am J Surg 2021 Jun 22. Epub 2021 Jun 22.

Department of Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address:

Introduction: We used interrupted time series (ITS) analysis to determine whether e-scooter shares' introduction in September 2017 increased serious scooter-related injury across the United States.

Methods: Using the National Electronic Injury Surveillance System, we queried emergency department visits involving motorized scooter-related injuries from January 2010-December 2019. Cases originating where e-scooter shares launched between September 1, 2017-December 1, 2019 (intervention period) were considered exposed. The first month of launch (September 2017) was chosen as the time point for pre- and post-intervention analysis. The primary outcome was change in hospitalizations following scooter injury in association with the month/year launch.

Results: This analysis includes 2754 unweighted encounters, representing 102614 estimated injuries involving motorized scooters nationwide. Hospitals within 20 miles of e-scooter shares also experienced a significant monthly increase of 0.24 scooter-related injury hospitalizations/1000 product-related injury hospitalizations ([0.17,0.31]) compared to a non-significant change in hospitalizations of 0.02 [-0.05,0.09] for control hospitals.

Conclusion: An increase in serious motorized scooter injuries coincides with e-scooter shares' introduction in the US. Future works should explore effective polices to improve public safety.
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http://dx.doi.org/10.1016/j.amjsurg.2021.06.006DOI Listing
June 2021

Powering Electronic Devices from Salt Gradients in AA-Battery-Sized Stacks of Hydrogel-Infused Paper.

Adv Mater 2021 Jun 24:e2101757. Epub 2021 Jun 24.

Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, Fribourg, 1700, Switzerland.

Strongly electric fish use gradients of ions within their bodies to generate stunning external electrical discharges; the most powerful of these organisms, the Atlantic torpedo ray, can produce pulses of over 1 kW from its electric organs. Despite extensive study of this phenomenon in nature, the development of artificial power generation schemes based on ion gradients for portable, wearable, or implantable human use has remained out of reach. Previously, an artificial electric organ inspired by the electric eel demonstrated that electricity generated from ion gradients within stacked hydrogels can exceed 100 V. The current of this power source, however, was too low to power standard electronics. Here, an artificial electric organ inspired by the unique morphologies of torpedo rays for maximal current output is introduced. This power source uses a hybrid material of hydrogel-infused paper to create, organize, and reconfigure stacks of thin, arbitrarily large gel films in series and in parallel. The resulting increase in electrical power by almost two orders of magnitude compared to the original eel-inspired design makes it possible to power electronic devices and establishes that biology's mechanism of generating significant electrical power can now be realized from benign and soft materials in a portable size.
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http://dx.doi.org/10.1002/adma.202101757DOI Listing
June 2021

Role of molecular signature to differentiate second primary lung cancer from metastasis in a patient with squamous cell carcinoma of oral cavity.

Cancer Rep (Hoboken) 2021 Jun 23:e1363. Epub 2021 Jun 23.

Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA.

Background: Lung is the most common site of distant metastasis for patients with head and neck squamous cell carcinoma (HNSCC). However, differentiating second primary lung cancers from metastasis may be difficult for p16 negative HNSCC.

Case: We describe a case of oral cavity squamous cell carcinoma (SCC) who was found to have lung nodule and hilar lymphadenopathy (LAD) after surgery and radiation therapy. Hilar node was consistent with SCC however, it was difficult to differentiate second primary lung cancer and metastasis from oral cavity SCC. Next-generation sequencing was done for the primary oral cavity and the hilar node. Both samples had the same type of TP53 mutation and variants of unknown significance suggesting metastatic HNSCC. He was treated with a chemotherapy regimen for metastatic HNSCC.

Conclusion: Molecular studies can help to differentiate metastasis from second primary lung cancers for p16 negative HNSCC.
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http://dx.doi.org/10.1002/cnr2.1363DOI Listing
June 2021

Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Stem Cells 2021 May 20. Epub 2021 May 20.

Department of Hematology, Oncology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFβ1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFβ1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFβ1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFβ receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFβ1, suggesting that blockage of this pathway may improve hematopoiesis in AML.
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http://dx.doi.org/10.1002/stem.3387DOI Listing
May 2021

Eligibility for clinical trials is unsatisfactory for patients with myelodysplastic syndromes, even at a tertiary referral center.

Leuk Res 2021 May 11;108:106611. Epub 2021 May 11.

Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.

Participation in clinical trials may allow patients with MDS to gain access to therapies not otherwise available. However, access is limited by strict inclusion and exclusion criteria, reflecting academic or regulatory questions addressed by the respective studies. We performed a simulation in order to estimate the average proportion of MDS patients eligible for participation in a clinical trial. The simulation drew upon 1809 patients in the Düsseldorf MDS Registry whose clinical data allowed eligibility screening for a wide range of clinical trials. This cohort was assumed to be alive and available for study participation. The simulation also posited that all MDS trials (n = 47) conducted in our center between 1987 and 2016 were open for recruitment. In addition, study activities in the year 2016 were analyzed to determine the proportion of patients eligible for at least one of the 9 MDS trials open at that time. On average, each clinical trial was suitable for about 18 % of patients in the simulation cohort. Conversely, 34 % of the patients were eligible for at least one of the 9 clinical studies in 2016. Inclusion/exclusion criteria of studies initiated by the pharmaceutical industry excluded more than twice the fraction of patients compared with investigator initiated trials (potential inclusion of 10 % vs. 21 %, respectively). Karyotype (average exclusion rate 58 %), comorbidities (40 %), and prior therapies (55 %) were the main reasons for exclusion. We suggest that in- and exclusion criteria should be less restrictive, in order to meet the needs of the real-life population of elderly MDS patients.
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http://dx.doi.org/10.1016/j.leukres.2021.106611DOI Listing
May 2021

Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS.

Eur J Haematol 2021 Aug 27;107(2):283-292. Epub 2021 May 27.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine - University, Duesseldorf, Germany.

Objective: As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS.

Methods: In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS).

Results: Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P = .008), RFS (P = .005), and OS (P = .049).

Conclusions: PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients.
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http://dx.doi.org/10.1111/ejh.13664DOI Listing
August 2021

Association between red blood cell transfusion dependence and burden in patients with myelodysplastic syndromes: A systematic literature review and meta-analysis.

Eur J Haematol 2021 Jul 14;107(1):3-23. Epub 2021 Apr 14.

Bristol Myers Squibb, Princeton, NJ, USA.

Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and transfusion dependency, with up to 30% of patients progressing to acute myeloid leukemia (AML). Studies suggest transfusion dependency may impact overall survival (OS); however, there is a lack of evidence concerning the association between transfusion status (TS) and OS in patients with MDS who become transfusion independent (TI) after treatment. In addition, the holistic impact of TS on other clinical, economic, and humanistic outcomes has not been well understood. We conducted a systematic literature review (SLR) to understand this impact. Ten studies were included and showed consistent decrease in OS in transfusion dependent (TD) compared with TI patients. These findings were confirmed by a meta-analysis (MA) reporting better OS prognosis for TI patients. A second SLR was conducted to understand the association between TS and other clinical, economic, and humanistic outcomes. Twenty-eight studies were included and showed better prognosis for other outcomes, including AML progression and leukemia-free survival for TI patients. Risk of AML progression and cumulative non-leukemic death assessed by the MA showed a trend toward worse prognosis and higher risk of AML progression for TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were observed. Studies not eligible for MA also showed better clinical, economic, and humanistic outcomes for TI patients. These findings contribute to understanding the association between transfusion dependence and OS among other outcomes in patients with MDS.
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http://dx.doi.org/10.1111/ejh.13619DOI Listing
July 2021

Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin.

Blood 2021 Jun;137(22):3093-3104

Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Germany.

In the international randomized phase 3 RATIFY (Randomized AML Trial In FLT3 in patients less than 60 Years old) trial, the multikinase inhibitor midostaurin significantly improved overall and event-free survival in patients 18 to 59 years of age with FLT3-mutated acute myeloid leukemia (AML). However, only 59% of patients in the midostaurin arm achieved protocol-specified complete remission (CR), and almost half of patients achieving CR relapsed. To explore underlying mechanisms of resistance, we studied patterns of clonal evolution in patients with FLT3-internal tandem duplications (ITD)-positive AML who were entered in the RATIFY or German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and received treatment with midostaurin. To this end, paired samples from 54 patients obtained at time of diagnosis and at time of either relapsed or refractory disease were analyzed using conventional Genescan-based testing for FLT3-ITD and whole exome sequencing. At the time of disease resistance or progression, almost half of the patients (46%) became FLT3-ITD negative but acquired mutations in signaling pathways (eg, MAPK), thereby providing a new proliferative advantage. In cases with FLT3-ITD persistence, the selection of resistant ITD clones was found in 11% as potential drivers of disease. In 32% of cases, no FLT3-ITD mutational change was observed, suggesting either resistance mechanisms bypassing FLT3 inhibition or loss of midostaurin inhibitory activity because of inadequate drug levels. In summary, our study provides novel insights into the clonal evolution and resistance mechanisms of FLT3-ITD-mutated AML under treatment with midostaurin in combination with intensive chemotherapy.
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http://dx.doi.org/10.1182/blood.2020007626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233666PMC
June 2021

Three-Dimensional Interfacing of Cells with Hierarchical Silicon Nano/Microstructures for Midinfrared Interrogation of In Situ Captured Proteins.

ACS Appl Mater Interfaces 2021 Feb 11;13(7):8049-8059. Epub 2021 Feb 11.

Department of Biology, University of Osnabrück, Osnabrück 49076, Germany.

Label-free optical detection of biomolecules is currently limited by a lack of specificity rather than sensitivity. To exploit the much more characteristic refractive index dispersion in the mid-infrared (IR) regime, we have engineered three-dimensional IR-resonant silicon micropillar arrays (Si-MPAs) for protein sensing. By exploiting the unique hierarchical nano- and microstructured design of these Si-MPAs attained by CMOS-compatible silicon-based microfabrication processes, we achieved an optimized interrogation of surface protein binding. Based on spatially resolved surface functionalization, we demonstrate controlled three-dimensional interfacing of mammalian cells with Si-MPAs. Spatially controlled surface functionalization for site-specific protein immobilization enabled efficient targeting of soluble and membrane proteins into sensing hotspots directly from cells cultured on Si-MPAs. Protein binding to Si-MPA hotspots at submonolayer level was unambiguously detected by conventional Fourier transform IR spectroscopy. The compatibility with cost-effective CMOS-based microfabrication techniques readily allows integration of this novel IR transducer into fully fledged bioanalytical microdevices for selective and sensitive protein sensing.
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http://dx.doi.org/10.1021/acsami.0c22421DOI Listing
February 2021

Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: results from the AMLSG 09-09 trial.

Blood 2020 12;136(26):3041-3050

Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.

Monitoring of measurable residual disease (MRD) provides prognostic information in patients with Nucleophosmin1-mutated (NPM1mut) acute myeloid leukemia (AML) and represents a powerful tool to evaluate treatment effects within clinical trials. We determined NPM1mut transcript levels (TLs) by quantitative reverse-transcription polymerase chain reaction and evaluated the prognostic impact of NPM1mut MRD and the effect of gemtuzumab ozogamicin (GO) on NPM1mut TLs and the cumulative incidence of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase 3 AMLSG 09-09 trial. A total of 3733 bone marrow (BM) samples and 3793 peripheral blood (PB) samples from 469 patients were analyzed. NPM1mut TL log10 reduction ≥ 3 and achievement of MRD negativity in BM and PB were significantly associated with a lower CIR rate, after 2 treatment cycles and at end of treatment (EOT). In multivariate analyses, MRD positivity was consistently revealed to be a poor prognostic factor in BM and PB. With regard to treatment effect, the median NPM1mut TLs were significantly lower in the GO-Arm across all treatment cycles, resulting in a significantly greater proportion of patients achieving MRD negativity at EOT (56% vs 41%; P = .01). The better reduction in NPM1mut TLs after 2 treatment cycles in MRD positive patients by the addition of GO led to a significantly lower CIR rate (4-year CIR, 29.3% vs 45.7%, P = .009). In conclusion, the addition of GO to intensive chemotherapy in NPM1mut AML resulted in a significantly better reduction in NPM1mut TLs across all treatment cycles, leading to a significantly lower relapse rate.
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http://dx.doi.org/10.1182/blood.2020005998DOI Listing
December 2020

Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents-a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group.

Ann Hematol 2021 Apr 16;100(4):959-968. Epub 2020 Nov 16.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.

Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1-19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRD, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.
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http://dx.doi.org/10.1007/s00277-020-04321-xDOI Listing
April 2021

Long-Term Survival Benefit after Allogeneic Hematopoietic Cell Transplantation for Chronic Myelomonocytic Leukemia.

Transplant Cell Ther 2021 01 9;27(1):95.e1-95.e4. Epub 2020 Oct 9.

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

The critical question in the management of chronic myelomonocytic leukemia (CMML) is which patients may benefit from allogeneic hematopoietic cell transplantation (allo-HCT). Using ad hoc statistical analysis, we designed a multicenter retrospective study to determine outcomes in 261 patients age ≤70 years at diagnosis who underwent allo-HCT (n = 119) compared with those who did not (n = 142) according to the current CMML-specific prognostic scoring system (CPSS). Categorizing patients as lower risk (CPSS low/intermediate-1) or higher risk (intermediate-2/high) showed significantly improved outcomes after transplantation in higher-risk patients, with a 37% reduced hazard for death. However, although higher CPSS was associated with worse outcomes in the nontransplantation group, the score was of limited utility for post-transplantation risk stratification. This study may provide further support for the potentially beneficial role of allo-HCT in terms of long-term survival in higher-risk patients but also underscores the need for transplantation-specific risk assessment. Recognizing limitations of retrospective comparisons, larger and prospective comparisons are needed to further refine the indication for allo-HCT and thus counseling of patients with CMML.
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http://dx.doi.org/10.1016/j.bbmt.2020.10.007DOI Listing
January 2021

Influence of somatic mutations and pretransplant strategies in patients allografted for myelodysplastic syndrome or secondary acute myeloid leukemia.

Am J Hematol 2021 01 30;96(1):E15-E17. Epub 2020 Oct 30.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine - University, Duesseldorf, Germany.

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http://dx.doi.org/10.1002/ajh.26013DOI Listing
January 2021

Strong Electron-Phonon Interaction in 2D Vertical Homovalent III-V Singularities.

ACS Nano 2020 Oct 1;14(10):13127-13136. Epub 2020 Oct 1.

Univ Rennes, INSA Rennes, CNRS, Institut FOTON-UMR 6082, F-35000 Rennes, France.

Highly polar materials are usually preferred over weakly polar ones to study strong electron-phonon interactions and its fascinating properties. Here, we report on the achievement of simultaneous confinement of charge carriers and phonons at the vicinity of a 2D vertical homovalent singularity (antiphase boundary, APB) in an (In,Ga)P/SiGe/Si sample. The impact of the electron-phonon interaction on the photoluminescence processes is then clarified by combining transmission electron microscopy, X-ray diffraction, calculations, Raman spectroscopy, and photoluminescence experiments. 2D localization and layer group symmetry properties of homovalent electronic states and phonons are studied by first-principles methods, leading to the prediction of a type-II band alignment between the APB and the surrounding semiconductor matrix. A Huang-Rhys factor of 8 is finally experimentally determined for the APB emission line, underlining that a large and unusually strong electron-phonon coupling can be achieved by 2D vertical quantum confinement in an undoped III-V semiconductor. This work extends the concept of an electron-phonon interaction to 2D vertically buried III-V homovalent nano-objects and therefore provides different approaches for material designs, vertical carrier transport, heterostructure design on silicon, and device applications with weakly polar semiconductors.
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http://dx.doi.org/10.1021/acsnano.0c04702DOI Listing
October 2020

Wilm's Tumor 1-guided preemptive treatment with hypomethylating agents for molecular relapse of AML and MDS after allogeneic transplantation.

Bone Marrow Transplant 2021 02 2;56(2):442-450. Epub 2020 Sep 2.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine-University, Duesseldorf, Germany.

Hypomethylating agents (HMA) for relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic transplantation (allo-SCT) are most effective when used at the stage of molecular relapse. As Wilm's Tumor 1 (WT1)- expression has proven to serve as broadly applicable, sensitive and specific minimal residual disease (MRD) marker, we measured WT1-expression in 35 AML and MDS patients using a standardized assay for the guidance of therapy with HMA and donor lymphocyte infusions (DLI). Molecular relapse was detected in median 168 days post-transplant prompting therapy with a median of six HMA cycles and at least one DLI (n = 22, 63%). Hereby, 13 patients (37%) achieved major response (=MRD complete remission [CR]), and 7 patients (20%) achieved minor response (=MRD CR), whereas 15 patients (43%) progressed into hematologic relapse. Two-year overall survival (OS) rate was 35% including 11 patients (31%) with ongoing MRD remission for a median of 21 months. Patients with the major response after six cycles had significantly better OS suggesting that those not achieving MRD negativity after six cycles are candidates for alternative therapies. Combining MRD-monitoring of WT1-expression and preemptive therapy with HMA and DLI appears as a practicable and efficient approach for imminent relapse after allo-SCT.
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http://dx.doi.org/10.1038/s41409-020-01039-2DOI Listing
February 2021

National Estimates of ENDS Liquid Nicotine Exposures, U.S., 2013-2017.

Am J Prev Med 2020 11 18;59(5):742-745. Epub 2020 Aug 18.

Center for Tobacco Products, U.S. Food and Drug Administration, Silver Spring, Maryland.

Introduction: Increased use of ENDS in the U.S. is related to acute adverse events from liquid nicotine exposure. This paper provides national estimates of U.S. hospital emergency department visits for exposures from liquid nicotine exposure in individuals aged ≥5 years.

Methods: In 2018-2019, data from the 2013-2017 National Electronic Injury Surveillance System All Injury Program were used to identify cases of liquid nicotine-related exposures in individuals aged ≥5 years. National estimates of exposures related to liquid nicotine exposure in ENDS for those aged ≥5 years by demographic characteristics, symptoms, diagnoses, and treatment dispositions were calculated.

Results: From 2013 to 2017, an estimated 2,718 cases related to liquid nicotine among those aged ≥5 years were treated in U.S. hospital emergency departments. Most exposures occurred among those who were aged ≥25 years (51.7%), white (74.1%), and male (51.9%). Most case patients were treated and released from the hospitals, and 7.5% were admitted. Poisoning was the most common diagnosis of these exposures (82.7%). The most common symptoms were cardiovascular (29.7%).

Conclusions: This study provides national estimates of emergency department visits for injury and poisoning cases related to nicotine exposure from ENDS among individuals aged ≥5 years. Although long-term health outcome studies of liquid nicotine exposure are not available, these estimates provide some insight into the acute health effects. Findings from this study may inform education programs aimed at preventing exposures related to ENDS products.
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http://dx.doi.org/10.1016/j.amepre.2020.05.027DOI Listing
November 2020

First Evaluation of PRISMA Level 1 Data for Water Applications.

Sensors (Basel) 2020 Aug 14;20(16). Epub 2020 Aug 14.

Institute of Marine Sciences, National Research Council of Italy (CNR-ISMAR), 00133 Rome, Italy.

This study presents a first assessment of the Top-Of-Atmosphere (TOA) radiances measured in the visible and near-infrared (VNIR) wavelengths from PRISMA (PRecursore IperSpettrale della Missione Applicativa), the new hyperspectral satellite sensor of the Italian Space Agency in orbit since March 2019. In particular, the radiometrically calibrated PRISMA Level 1 TOA radiances were compared to the TOA radiances simulated with a radiative transfer code, starting from in situ measurements of water reflectance. In situ data were obtained from a set of fixed position autonomous radiometers covering a wide range of water types, encompassing coastal and inland waters. A total of nine match-ups between PRISMA and in situ measurements distributed from July 2019 to June 2020 were analysed. Recognising the role of Sentinel-2 for inland and coastal waters applications, the TOA radiances measured from concurrent Sentinel-2 observations were added to the comparison. The results overall demonstrated that PRISMA VNIR sensor is providing TOA radiances with the same magnitude and shape of those in situ simulated (spectral angle difference, SA, between 0.80 and 3.39; root mean square difference, RMSD, between 0.98 and 4.76 [mW m sr nm]), with slightly larger differences at shorter wavelengths. The PRISMA TOA radiances were also found very similar to Sentinel-2 data (RMSD < 3.78 [mW m sr nm]), and encourage a synergic use of both sensors for aquatic applications. Further analyses with a higher number of match-ups between PRISMA, in situ and Sentinel-2 data are however recommended to fully characterize the on-orbit calibration of PRISMA for its exploitation in aquatic ecosystem mapping.
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http://dx.doi.org/10.3390/s20164553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471993PMC
August 2020

Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation.

Cancers (Basel) 2020 Aug 12;12(8). Epub 2020 Aug 12.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine-University, Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.

To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after a median of 4 cycles and lasted for a median of 11 months (range 0.9 to 120 months). With a median follow-up of 22 months (range: 1 to 122 months), the 2-year survival rate was 38% ± 9%, including 17 patients with ongoing remission for >5 years. Based on results from multivariate analyses, molecular relapse and time to relapse were integrated into a score, clearly dividing patients into 3 subgroups with CR rates of 71%, 39%, and 29%; and 2-year survival rates of 64%, 38%, and 27%, respectively. In the subgroup of MDS and secondary AML, receiving upfront transplantation was associated with superior response and survival, and therefore pretransplant strategy was integrated together with relapse type into a MDS-sAML-specific score. Overall, Aza enables meaningful responses and long-term survival, which is a predictable with a simple-to-use scoring system.
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http://dx.doi.org/10.3390/cancers12082255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464210PMC
August 2020

Conceptual framework for precision cancer medicine in Germany: Consensus statement of the Deutsche Krebshilfe working group 'Molecular Diagnostics and Therapy'.

Eur J Cancer 2020 08 7;135:1-7. Epub 2020 Jun 7.

University Comprehensive Cancer Center Hamburg, Department of Oncology, Hematology with Section Bone Marrow Transplantation and Pneumology, University Medical Center Hamburg-Eppendorf, Germany. Electronic address:

Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany. With support of the 'German Cancer Aid' (Deutsche Krebshilfe [DKH]) a task force 'Molecular Diagnostics and Therapy' was implemented. In two workshops supported by the DKH, delegates from the fourteen comprehensive cancer centresidentified key topics essential to implement quality-guided, harmonized and adaptable PCM. Based on an online questionnaire and using a modified Delphi approach, nine statements were drafted and evaluated within the group. These statements could serve as a basis to define a collaborative strategy for PCM in the future with the aim to sustain and further improve its quality.
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http://dx.doi.org/10.1016/j.ejca.2020.04.019DOI Listing
August 2020

Ge(Sn) nano-island/Si heterostructure photodetectors with plasmonic antennas.

Nanotechnology 2020 Aug 11;31(34):345203. Epub 2020 May 11.

Peter Grünberg Institute (PGI 10), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, Jülich 52425, Germany. IHP - Leibniz-Institut für innovative Mikroelektronik, Im Technologiepark 25, Frankfurt (Oder) D-15236, Germany.

We report on photodetection in deep subwavelength Ge(Sn) nano-islands on Si nano-pillar substrates, in which self-aligned nano-antennas in the Al contact metal are used to enhance light absorption by means of local surface plasmon resonances. The impact of parameters such as substrate doping and device geometry on the measured responsivities are investigated and our experimental results are supported by simulations of the three-dimensional distribution of the electromagnetic fields. Comparatively high optical responsivities of about 0.1 A W are observed as a consequence of the excitation of localized surface plasmons, making our nano-island photodetectors interesting for applications in which size reduction is essential.
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http://dx.doi.org/10.1088/1361-6528/ab91efDOI Listing
August 2020

Toward a Reliable Synaptic Simulation Using Al-Doped HfO RRAM.

ACS Appl Mater Interfaces 2020 Mar 20;12(9):10648-10656. Epub 2020 Feb 20.

Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education & International Center for Dielectric Research, School of Electronic Science and Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

The potential in a synaptic simulation for neuromorphic computation has revived the research interest of resistive random access memory (RRAM). However, novel applications require reliable multilevel resistive switching (RS), which still represents a challenge. We demonstrate in this work the achievement of reliable HfO-based RRAM devices for synaptic simulation by performing the Al doping and the postdeposition annealing (PDA). Transmission electron microscopy and operando hard X-ray photoelectron spectroscopy results reveal the positive impact of Al doping on the formation of oxygen vacancies. Detailed - characterizations demonstrate that the 16.5% Al doping concentration leads to better RS properties of the device. In comparison with the other reported results based on HfO RRAM, our devices with 16.5% Al-doping and PDA at 450 °C show better reliable multilevel RS (∼20 levels) performance and an increased on/off ratio. The 16.5% Al:HfO sample with PDA at 450 °C shows good potentiation/depression characteristics with low pulse width (10 μs) along with a good On/Off ratio (>1000), good data retention at room temperature, and high temperature and good program/erase endurance characteristics with a pulse width of 50 ns. The synapse features including potentiation, depression, and spike time-dependent plasticity were successfully achieved using optimized Al-HfO RRAM devices. Our results demonstrate the beneficial effects of Al doping and PDA on the enhancement of the performances of RRAM devices for the synaptic simulation in neuromorphic computing applications.
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http://dx.doi.org/10.1021/acsami.9b21530DOI Listing
March 2020

Gemtuzumab Ozogamicin in -Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study.

J Clin Oncol 2020 02 18;38(6):623-632. Epub 2019 Dec 18.

Department of Hematology, Hemostaseology, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Purpose: High CD33 expression in acute myeloid leukemia (AML) with mutated provides a rationale for the evaluation of gemtuzumab ozogamicin (GO) in this AML entity. We conducted a randomized trial to evaluate GO in combination with intensive induction and consolidation therapy in -mutated AML.

Patients And Methods: Between May 2010 and September 2017, patients ≥ 18 years old and considered eligible for intensive therapy were randomly assigned up front for induction therapy with idarubicin, cytarabine, etoposide, and all--retinoic acid with or without GO. The early ( = .02) primary end point of event-free survival (EFS) was evaluated 6 months after completion of patient recruitment.

Results: Five hundred eighty-eight patients were randomly assigned (standard arm, n = 296; GO arm, n = 292). EFS in the GO arm was not significantly different compared with that in the standard arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.04; = .10). The early death rate during induction therapy was 10.3% in the GO arm and 5.7% in the standard arm ( = .05). Causes of death in both arms were mainly infections. The cumulative incidence of relapse (CIR) in patients achieving a complete remission (CR) or CR with incomplete hematologic recovery (CRi) was significantly reduced in the GO arm compared with the standard arm ( = .005), with no difference in the cumulative incidence of death ( = .80). Subgroup analysis revealed a significant beneficial effect of GO in female, younger (≤ 70 years), and internal tandem duplication-negative patients with respect to EFS and CIR.

Conclusion: The trial did not meet its early primary end point of EFS, mainly as a result of a higher early death rate in the GO arm. However, in patients achieving CR/CRi after induction therapy, significantly fewer relapses occurred in the GO compared with the standard arm.
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http://dx.doi.org/10.1200/JCO.19.01406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030890PMC
February 2020

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

Blood Cancer J 2019 11 12;9(11):86. Epub 2019 Nov 12.

Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.
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http://dx.doi.org/10.1038/s41408-019-0248-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851368PMC
November 2019

Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group.

Blood 2019 11;134(19):1608-1618

Klinik für Innere Medizin III, Universitätsklinikum Ulm, Ulm, Germany.

We performed serial measurable residual disease (MRD) monitoring in bone marrow (BM) and peripheral blood (PB) samples of 155 intensively treated patients with RUNX1-RUNX1T1+ AML, using a qRT-PC-based assay with a sensitivity of up to 10-6. We assessed both reduction of RUNX1-RUNX1T1 transcript levels (TLs) and achievement of MRD negativity (MRD-) for impact on prognosis. Achievement of MR2.5 (>2.5 log reduction) after treatment cycle 1 and achievement of MR3.0 after treatment cycle 2 were significantly associated with a reduced risk of relapse (P = .034 and P = .028, respectively). After completion of therapy, achievement of MRD- in both BM and PB was an independent, favorable prognostic factor in cumulative incidence of relapse (4-year cumulative incidence relapse: BM, 17% vs 36%, P = .021; PB, 23% vs 55%, P = .001) and overall survival (4-year overall survival rate BM, 93% vs 70%, P = .007; PB, 87% vs 47%, P < .0001). Finally, during follow-up, serial qRT-PCR analyses allowed prediction of relapse in 77% of patients exceeding a cutoff value of 150 RUNX1-RUNX1T1 TLs in BM, and in 84% of patients exceeding a value of 50 RUNX1-RUNX1T1 TLs in PB. The KIT mutation was a significant factor predicting a lower CR rate and inferior outcome, but its prognostic impact was outweighed by RUNX1-RUNX1T1 TLs during treatment. Virtually all relapses occurred within 1 year after the end of treatment, with a very short latency from molecular to morphologic relapse, necessitating MRD assessment at short intervals during this time period. Based on our data, we propose a refined practical guideline for MRD assessment in RUNX1-RUNX1T1+ AML.
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http://dx.doi.org/10.1182/blood.2019001425DOI Listing
November 2019

UV-NIR approach with non-zero water-leaving radiance approximation for atmospheric correction of satellite imagery in inland and coastal zones.

Opt Express 2019 Aug;27(16):A1118-A1145

In the atmospheric correction process of the satellite ocean color data, the removal of the aerosol scattering contribution over the coastal and inland water bodies has been a major challenge with the standard algorithms. In this work, a practical method is proposed based on a combination of NIR and ultraviolet (UV) bands (named as UVNIR-ex) for the succeeding generation of space borne multispectral and hyperspectral sensors. This scheme replaces the black-ocean assumption and accounts for non-zero water-leaving radiance contributions in the NIR and UV bands. The aerosol contributions are thus deduced for these two bands and used to select the appropriate aerosol models to retrieve aerosol optical properties and hence, water-leaving radiances in the UV, Visible and NIR bands. The performance of the UVNIR-ex algorithm was tested and evaluated based on match-ups between HICO and in-situ observations in optically complex coastal and inland waters and by comparison with three alternative aerosol correction methods based on UV-NIR, Spectral Shape Parameter (SSP) and iterative NIR (INIR) approaches. A preliminary comparison with in-situ aerosol optical thickness (AOT) measurements from AERONET-OC sites revealed that the UVNIR-ex algorithm significantly improved the AOT retrievals with a mean relative error (MRE) around 25%, while the UVNIR, SSP and INIR algorithms showed performance degradation with a MRE of 27%, 34%, and 42%, respectively. The comparison with AERONET-OC and regional in-situ measurements from turbid and productive waters further showed that the INIR algorithm underestimated the retrievals in blue bands in turbid waters (MRE > 100%) and negligible in red-NIR bands and high anomalous radiances in UV-Blue bands in productive waters (MRE 53%). The SSP and UVNIR algorithms performed better in retrieving the in green-NIR bands but showed significant errors in UV-blue bands in both turbid and productive waters. Based on these match-up analyses, the UVNIR-ex algorithm yielded best retrievals across all the UV-NIR bands in terms of accuracy and performance. The highest accuracy and consistency of the UVNIR-ex algorithm indicates that it is more suited for estimating the aerosol optical properties and water-leaving radiance and has a significant advantage over the requirement of shortwave infrared bands for turbid and productive waters.
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http://dx.doi.org/10.1364/OE.27.0A1118DOI Listing
August 2019

Daratumumab for treatment of pure red cell aplasia after allogeneic stem cell transplantation.

Bone Marrow Transplant 2020 06 3;55(6):1191-1193. Epub 2019 Sep 3.

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.

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http://dx.doi.org/10.1038/s41409-019-0664-4DOI Listing
June 2020
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