Blastic plasmacytoid dendritic cell neoplasm: a single-center experience. Clinical characterization, mutational landscape, and clinical outcome of patients undergoing hematopoietic stem cell transplantation intensive therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.

Long-term outcomes of rituximab therapy in pemphigus.

BACKGROUND: Rituximab induces a rapid remission in most patients with pemphigus. OBJECTIVE: Our aim was to assess the long-term efficacy of rituximab in this disease. METHOD: We conducted a retrospective study of 59 patients with pemphigus treated with rituximab and observed over a median period of 104 months. RESULTS: The rate of complete remission off therapy (CRoff) after the first rituximab cycle was 39%, increasing to 61% with additional rituximab courses. Long-term CRoff was achieved in 27% of patients. The recurrence rate after the first rituximab cycle was 63%, decreasing to approximately 40% with subsequent rituximab cycles. Median time to relapse after the first and subsequent rituximab cycles was 25 months. Renewed rituximab therapy reinduced complete remission in 94% of cases. Baseline anti-desmoglein antibody levels of ≤250 U/mL were significantly associated with the outcome of CRoff. In paired serum samples obtained before the first and six months after the last rituximab therapy, significant reductions of desmoglein-specific autoantibodies were observed. Patients relapsing after a complete remission induced by the first rituximab cycle were more likely to achieve CRoff than patients relapsing after a less favourable outcome and non-responders. There was no significant difference in age, sex, pemphigus subtype, rituximab dosing and disease duration between patients achieving CRoff and those not meeting this end point. CONCLUSIONS: Lower desmoglein-specific antibody levels at baseline were predictive of CRoff. In patients receiving multiple rituximab cycles, complete remission after the first cycle was associated with a favourable long-term outcome. Repeated rituximab courses were highly effective for relapsed disease and improved the overall outcome.

Constraining the Neutron Star Compactness: Extraction of the

The ^{23}Al(p,γ)^{24}Si reaction is among the most important reactions driving the energy generation in type-I x-ray bursts. However, the present reaction-rate uncertainty limits constraints on neutron star properties that can be achieved with burst model-observation comparisons. Here, we present a novel technique for constraining this important reaction by combining the GRETINA array with the neutron detector LENDA coupled to the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The ^{23}Al(d,n) reaction was used to populate the astrophysically important states in ^{24}Si. This enables a measurement in complete kinematics for extracting all relevant inputs necessary to calculate the reaction rate. For the first time, a predicted close-lying doublet of a 2_{2}^{+} and (4_{1}^{+},0_{2}^{+}) state in ^{24}Si was disentangled, finally resolving conflicting results from two previous measurements. Moreover, it was possible to extract spectroscopic factors using GRETINA and LENDA simultaneously. This new technique may be used to constrain other important reaction rates for various astrophysical scenarios.

[The pathologist Friedrich Feyrter in National Socialism]. / Der Pathologe Friedrich Feyrter im Nationalsozialismus.

BACKGROUND: Up until now, very little has been reported about the important pathologist Friedrich Feyrter in the time of National Socialism. OBJECTIVES: What was Feyrter's attitude towards National Socialism? METHODS: Bibliographic and previously unevaluated archival sources were subjected to a historical-critical examination. RESULTS: Feyrter was a member of the Nazi Party. In 1938 and 1950 he gave contradictory information concerning the year he joined the party. CONCLUSIONS: At the very least, he was a political opportunist.

Control of H_{2} Dissociative Ionization in the Nonlinear Regime Using Vacuum Ultraviolet Free-Electron Laser Pulses.

The role of the nuclear degrees of freedom in nonlinear two-photon single ionization of H_{2} molecules interacting with short and intense vacuum ultraviolet pulses is investigated, both experimentally and theoretically, by selecting single resonant vibronic intermediate neutral states. This high selectivity relies on the narrow bandwidth and tunability of the pulses generated at the FERMI free-electron laser. A sustained enhancement of dissociative ionization, which even exceeds nondissociative ionization, is observed and controlled as one selects progressively higher vibronic states. With the help of ab initio calculations for increasing pulse durations, the photoelectron and ion energy spectra obtained with velocity map imaging allow us to identify new photoionization pathways. With pulses of the order of 100 fs, the experiment probes a timescale that lies between that of ultrafast dynamical processes and that of steady state excitations.

Erosive effect of different dietary substances on deciduous and permanent teeth.

OBJECTIVES: We investigated the effect of different dietary substances on deciduous and permanent enamel. MATERIALS AND METHODS: Enamel specimens were prepared from human teeth (n = 108 deciduous molars and n = 108 permanent premolars). We measured the chemical parameters (pH, titratable acidity, viscosity, calcium, phosphate, fluoride concentration and degree of saturation) of nine dietary substances. The teeth were immersed in the respective substance (2 × 2 min; 30 °C; shaking), and we measured the baseline surface hardness (SH) in Vickers hardness numbers (VHN), and the changes in SH after 2 min (ΔSH2-0) and the 4 min (ΔSH4-0) immersion. We analysed the differences between deciduous and permanent teeth using the Wilcoxon test and correlated ΔSH to the different chemical parameters. RESULTS: Deciduous teeth were significantly softer (549.53 ± 59.41 VHN) than permanent teeth (590.15 ± 55.31 VHN; p < 0.001) at baseline, but they were not more vulnerable to erosive demineralization. Only orange juice, which presented milder erosive potential, caused significantly more demineralisation in deciduous teeth at ΔSH4-0. Practically all chemical parameters significantly correlated with ΔSH (p < 0.05). Substances with lower pH, higher titratable acidity, lower Ca, higher Pi and lower F concentrations, higher viscosity and more undersaturated solutions presented more erosive demineralisation. CONCLUSION: Different parameters in dietary substances affect erosive demineralisation in deciduous and permanent teeth, but we generally observed no differences in susceptibility to erosion between both types of teeth; only orange juice (less severe acid conditions) caused perceptible differences. CLINICAL RELEVANCE: We observe that permanent teeth are harder than deciduous teeth, but most substances cause no perceptible difference in erosive demineralisation in both types of teeth.

[Structure of pain management facilities in Germany : Classification of medical and psychological pain treatment services-Consensus of the Joint Commission of the Professional Societies and Organizations for Quality in Pain Medicine]. / Struktur der schmerzmedizinischen Versorgung in Deutschland : Klassifikation schmerzmedizinischer Einrichtungen - Konsens der Gemeinsamen Kommission der Fachgesellschaften und Verbände für Qualität in der Schmerzmedizin.

On behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.

Aneurysmal bone cyst (ABC) : treatment options and proposal of a follow-up regime.

The aim of this study was to describe treatment -options and develop a follow-up regime for the -aneurysmal bone cyst, a neoplastic bone lesion with a noticeable recurrence rate. Reports of 28 patients and a mean follow-up of 42.2 months treated multidisciplinary were analysed. Data were complemented by a literature review including 790 patients. Patient age was from seven to 57 years, in line with the literature (1-69 years). Lesions most frequently affect long bones, spine and pelvis ; pain is the most common symptom. Treatment modalities vary, recurrences -occurred in 26.1% in our series, rates ranged from 0-60% in the literature, with the vast majority within 2 years. With regard to the findings we propose, irrespective of treatment, a follow-up regime including clinical survey and imaging, best with MRI, at 3 months, 6 months and at half-yearly intervals within the first two and yearly within the third to fifth year.

Post-mortem assessment of the short and long-term effects of the trophic factor neurturin in patients with α-synucleinopathies.

Substantial interest persists for developing neurotrophic factors to treat neurodegenerative diseases. At the same time, significant progress has been made in implementing gene therapy as a means to provide long-term expression of bioactive neurotrophic factors to targeted sites in the brain. Nonetheless, to date, no double-blind clinical trial has achieved positive results on its primary endpoint despite robust benefits achieved in animal models. A major issue with advancing the field is the paucity of information regarding the expression and effects of neurotrophic factors in human neurodegenerative brain, relative to the well-characterized responses in animal models. To help fill this information void, we examined post-mortem brain tissue from four patients with nigrostriatal degeneration who had participated in clinical trials testing gene delivery of neurturin to the putamen of patients. Each had died of unrelated causes ranging from 1.5-to-3-months (2 Parkinson's disease patients), to 4+-years (1 Parkinson's disease and 1 multiple-system atrophy-parkinsonian type patient) following gene therapy. Quantitative and immunohistochemical evaluation of neurturin, alpha-synuclein, tyrosine hydroxylase (TH) and an oligodendroglia marker (Olig 2) were performed in each brain. Comparable volumes-of-expression of neurturin were seen in the putamen in all cases (~15-22%; mean=18.5%). TH-signal in the putamen was extremely sparse in the shorter-term cases. A 6-fold increase was seen in longer-term cases, but was far less than achieved in animal models of nigrostriatal degeneration with similar or even far less NRTN exposure. Less than 1% of substantia nigra (SN) neurons stained for neurturin in the shorter-term cases. A 15-fold increase was seen in the longer-term cases, but neurturin was still only detected in ~5% of nigral cells. These data provide unique insight into the functional status of advanced, chronic nigrostriatal degeneration in human brain and the response of these neurons to neurotrophic factor stimulation. They demonstrate mild but persistent expression of gene-mediated neurturin over 4-years, with an apparent, time-related amplification of its transport and biological effects, albeit quite weak, and provide unique information to help plan and design future trials.

[Fusion of Continuously Moving Table MRI and PET Improves Lesion Detection in Recurrent Rectal Cancer]. / Kombination von MRT und PET erlaubt genauere Rezidivdiagnostik des Rektumkarzinoms durch Bildfusion.

PURPOSE: It was the aim of this study to investigate the complementary diagnostic performance of a combined pelvic and thoracoabdominal magnetic resonance imaging (MRI) examination and positron emission tomography (PET) enhanced by image fusion in patients with suspected rectal cancer recurrence. PATIENTS AND METHODS: Thirty-one patients with clinically suspected recurrence from rectal cancer were retrospectively included, who had received MRI (high resolution pelvic MRI combined with thoracoabdominal MRI performed during continuous table translation) and (18)F-FDG-PET within 30 days. MRI alone, PET alone, and MRI and PET combined including fusion images were analysed by two observers in consensus. The likelihood of malignancy of all detectable lesions was rated on a 5-point Likert scale. The standard of reference consisted of histopathology and follow-up imaging. Confidence ratings were analysed with a jackknife free response receiver-operator characteristic paradigm (JAFROC). Further test characteristics were derived by considering "probably malignant" and "definitely malignant" lesions as positive test results. RESULTS: The reference standard comprised 150 malignant lesions (48 local, 102 distant). JAFROC analysis revealed overall figures-of-merit of 0.73 for MRI, 0.63 for PET, and 0.83 for the combined approach (differences significant). The sensitivities of MRI, PET and the combined approach were 85.4, 52.1, and 95.8 % for local recurrence and 61.8, 47.1, and 81.4 % for distant recurrence, respectively. CONCLUSION: The combination of local high-resolution MRI, thoracoabdominal continuously moving table MRI and FDG-PET supported by image fusion improves lesion detection in recurrent rectal cancer.

[Current reporting in radiology : what will happen tomorrow?]. / Befundung in der Radiologie heute : Was kommt morgen?

CLINICAL/METHODICAL ISSUE: Reporting in radiology faces considerable changes in the near future that will be influenced by a broader understanding of the task and increasing technological possibilities. STANDARD RADIOLOGICAL METHODS: Until now a radiological report could be regarded as a text phrased by a radiologist after viewing imaging data. METHODICAL INNOVATIONS: New solutions will be accessed by advances in visualization of large datasets, in extracting, analyzing, and communicating metadata as well as by improved integration and interpretation of clinical information. PERFORMANCE: Virtual reality, texture analysis, growing networks, semantic annotation, data mining and context based presentation have the potential to extensively change the everyday working routine. ACHIEVEMENTS: Although many of these developments are still in a laboratory phase, the impact on the process of reporting can already be predicted. PRACTICAL RECOMMENDATIONS: As the leading community in information analysis and technology, radiology as a subject should strive to lead and shape these impending changes.

Study of two-neutron radioactivity in the decay of 26O.

A new technique was developed to measure the lifetimes of neutron unbound nuclei in the picosecond range. The decay of 26O→24O+n+n was examined as it had been predicted to have an appreciable lifetime due to the unique structure of the neutron-rich oxygen isotopes. The half-life of 26O was extracted as 4.5(-1.5)(+1.1)(stat)±3(syst) ps. This corresponds to 26O having a finite lifetime at an 82% confidence level and, thus, suggests the possibility of two-neutron radioactivity.

Unraveling the potential and pore-size dependent capacitance of slit-shaped graphitic carbon pores in aqueous electrolytes.

Understanding and leveraging physicochemical processes at the pore scale are believed to be essential to future performance improvements of supercapacitors and capacitive desalination (CD) cells. Here, we report on a combination of electrochemical experiments and fully atomistic simulations to study the effect of pore size and surface charge density on the capacitance of graphitic nanoporous carbon electrodes. Specifically, we used cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to study the effect of potential and pore size on the capacitance of nanoporous carbon foams. Molecular dynamics simulations were performed to study the pore-size dependent accumulation of aqueous electrolytes in slit-shaped graphitic carbon pores of different widths (0.65 to 1.6 nm). Experimentally, we observe a pronounced increase of the capacitance of sub-nm pores as the applied potential window gets wider, from a few F g(-1) for narrow potential ranges (-0.3 to 0.3 V vs. Ag/AgCl) to ~40 F g(-1) for wider potential windows (-0.9 V to 0.9 V vs. Ag/AgCl). By contrast, the capacitance of wider pores does not depend significantly on the applied potential window. Molecular dynamics simulations confirm that the penetration of ions into pores becomes more difficult with decreasing pore width and increasing strength of the hydration shell. Consistent with our experimental results, we observe a pore- and ion-size dependent threshold-like charging behavior when the pore width becomes comparable to the size of the hydrated ion (0.65 nm pores for Na(+) and 0.79 nm pores for Cl(-) ions). The observed pore-size and potential dependent accumulation of ions in slit-shaped carbon pores can be explained by the hydration structure of the ions entering the charged pores. The results are discussed in view of their effect on energy-storage and desalination efficiency.

Discovery of 40Mg and 42Al suggests neutron drip-line slant towards heavier isotopes.

A fundamental question in nuclear physics is what combinations of neutrons and protons can make up a nucleus. Many hundreds of exotic neutron-rich isotopes have never been observed; the limit of how many neutrons a given number of protons can bind is unknown for all but the lightest elements, owing to the delicate interplay between single particle and collective quantum effects in the nucleus. This limit, known as the neutron drip line, provides a benchmark for models of the atomic nucleus. Here we report a significant advance in the determination of this limit: the discovery of two new neutron-rich isotopes--40Mg and 42Al--that are predicted to be drip-line nuclei. In the past, several attempts to observe 40Mg were unsuccessful; moreover, the observation of 42Al provides an experimental indication that the neutron drip line may be located further towards heavier isotopes in this mass region than is currently believed. In stable nuclei, attractive pairing forces enhance the stability of isotopes with even numbers of protons and neutrons. In contrast, the present work shows that nuclei at the drip line gain stability from an unpaired proton, which narrows the shell gaps and provides the opportunity to bind many more neutrons.

[Image post-processing, part 1: visualization and segmentation]. / Bildnachverarbeitung Teil 1: Visualisierung und Segmentierung.

Image post-processing of large thin-slice radiological datasets relies on increasingly diverse and complex algorithms. Basic techniques of visualization, segmentation and data analysis will be presented in this article focusing on methods which are integrated into the majority of current viewing and reporting tools, such as multiplanar reformation, volume rendering or basic segmentation. Subsequently, more complex methods and a possible role of post-processing algorithms in the radiology of the future will be discussed.

[Image postprocessing part 2: algorithms and workflow]. / Bildnachverarbeitung Teil 2: Algorithmen und Workflow.

Apart from various display options, a large variety of complex algorithms to analyze radiological datasets have become available by means of advanced visualization. Basic knowledge of common concepts and properties allows the physician to choose and employ these algorithms more efficiently and successfully. In addition to functionality alone, the seamless integration of these methods into the radiological workflow is of special importance. Different scenarios can be implemented to achieve this integration. Detailed information on the individual goals of an installation and on the existing infrastructure represent prerequisites for successful integration.

[Examinations of cattle births with a special focus on Coxiella burnetii]. / Geburten an der Wiederkäuerklinik mit Fokus auf die Ausscheidung von Coxiella burnetii.

INTRODUCTION: Cattle births can carry the risk of transmissible and zoonotic diseases. The focus of the present study was the excretion of Coxiella (C.) burnetii during cattle births. Small ruminants are considered as the main reservoir of C. burnetii. Cattle are often subclinical carriers and their role as potential reservoir has not been fully elucidated until now, although the excretion of Coxiella has been demonstrated during cattle birth. The study recorded all births, caesarean sections and one abortion in 40 cattle at the ruminant clinic of the Vetsuisse Faculty in Bern in the study period from March 2019 to March 2020. A placenta -, milk - and fecal sample was examined for antigen diagnostics using polymerase chain reaction (PCR). In addition, a serum sample was analyzed to detect C. burnetii-specific antibodies. Antigen and/or antibodies (placenta, n=8/9; milk, n=2/9; faeces, n=1/9; serology n= 3/9) were detected in 22,5 % of the cows (n=9/40) without the presence of specific clinical symptoms. It is essential to sensitize contact persons to this zoonosis, since Coxiella can trigger Q-fever in humans.

INTRODUCTION: Les naissances chez les bovins peuvent comporter un risque de maladies transmissibles et zoonotiques. La présente étude se concentre sur l'excrétion de Coxiella (C.) burnetii lors des mises-bas de bovins. Les petits ruminants sont considérés comme le principal réservoir de C. burnetii, mais les bovins sont souvent des porteurs subcliniques et leur rôle de réservoir potentiel n'a pas été complètement élucidé jusqu'à présent, bien que l'excrétion de Coxiella ait été démontrée lors de la mise-bas. L'étude a recensé toutes les naissances, les césariennes et un avortement chez 40 bovins à la Clinique des ruminants de la Faculté Vetsuisse de Berne durant la période allant de mars 2019 à mars 2020. Un échantillon de placenta, de lait et de matières fécales a été examiné pour le diagnostic des antigènes par réaction en chaîne par polymérase (PCR). En outre, un échantillon de sérum a été analysé pour détecter les anticorps spécifiques de C. burnetii. L'antigène et/ou les anticorps (placenta, n=8/9 ; lait, n=2/9 ; fèces, n=1/9 ; sérologie n=3/9) ont été détectés chez 22,5 % des vaches (n=9/40) sans présence de symptômes cliniques spécifiques. Il est essentiel de sensibiliser les personnes de contact à cette zoonose, car Coxiella peut déclencher la fièvre Q chez l'homme.

Range verification in heavy-ion therapy using a hadron tumour marker.

Objective.A new method to estimate the range of an ion beam in a patient during heavy-ion therapy was investigated, which was previously verified for application in proton therapy.Approach.The method consists of placing a hadron tumour marker (HTM) close to the tumour. As the treatment beam impinges on the HTM, the marker undergoes nuclear reactions. When the HTM material is carefully chosen, the activation results in the emission of several delayed, characteristicγrays, whose intensities are correlated with the remaining range inside the patient. When not just one but two reaction channels are investigated, the ratio between these twoγray emissions can be measured, and the ratio is independent of any beam delivery uncertainties.Main results.A proof-of-principle experiment with an16O ion beam and Ag foils as HTM was successfully executed. The107Ag(16O,x)112Sb and the107Ag(16O,x)114Sb reaction channels were identified as suitable for the HTM technique. When only oneγ-ray emission is measured, the resulting range-uncertainty estimation is at the 0.5 mm scale. When both channels are considered, a theoretical limit on the range uncertainty of a clinical fiducal marker was found to be ±290µm.Significance.Range uncertainty of a heavy-ion beam limits the prescribed treatment plan for cancer patients, especially the direction of the ion beam in relation to any organ at risk. An easy to implement range-verification technique which can be utilized during clinical treatment would allow treatment plans to take full advantage of the sharp fall-off of the Bragg peak without the risk of depositing excessive dose into healthy tissue.