Efficacy and feasibility of proton beam therapy in relapsed high-risk neuroblastoma-experiences from the prospective KiProReg registry

BACKGROUND: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to reduce tumor burden and improve chance for disease control. METHODS: Patients who received salvage irradiation with proton beam therapy (PBT) for local or metastatic relapse of HR NB within the prospective registry trials KiProReg and ProReg were eligible for this retrospective analysis. Data on patient characteristics, multimodality therapy, adverse events, and oncologic endpoints were evaluated. Adverse events were assessed before, during, and after PBT according to common terminology criteria for adverse events (CTCAE) V4.0. RESULTS: Between September 2013 and September 2020, twenty (11 male; 9 female) consecutive patients experiencing local (N = 9) or distant recurrence (N = 25) were identified for this analysis. Distant recurrences included osteomedullary (N = 11) or CNS lesions (N = 14). Salvage therapy consisted of re-induction chemo- or chemo-immuno-therapy (N = 19), surgery (N = 6), high-dose chemotherapy and stem cell transplantation (N = 13), radiation (N = 20), and concurrent systemic therapy. Systemic therapy concurrent to RT was given to six patients and included temozolomide (N = 4), carboplatine (N = 1), or anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKI) (N = 1). A median dose of 36 Gy was applied to the 34 recurrent sites. Local RT was applied to 15 patients, while five patients, received craniospinal irradiation for CNS relapse. After a median follow-up (FU) of 20 months (4-66), the estimated rate for local control, distant metastatic free survival, and overall survival at 3 years was 68.0%, 37.9%, and 61.6%, respectively. During RT, ten patients (50%) presented with a higher-grade acute hematologic adverse event. Late higher-grade sequelae included transient myelitis with transverse section (N = 2) and secondary malignancy outside of the RT field (N = 1). CONCLUSION: Our study demonstrates the efficacy and safety of RT/PBT for recurrent HR NB in a multimodality second-line approach. To better define the role of RT for these patients, prospective studies would be desirable

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities

PURPOSE The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA

BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection

Background Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7 alpha-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization. Aim To analyze baiCD gene abundance in C. difficile positive and negative fecal samples. Material & methods A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes. Results The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64;p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor. Conclusion Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI

Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases

Importance of pre-enrichment for detection of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) from rectal swabs

Screening for multidrug-resistant Enterobacteriaceae is performed in many institutions as part of infection control measures. However, the sensitivity of current standard diagnostics is modest. Furthermore, patients are usually screened by rectal swabs (mostly rayon based), which have been shown to be sub-optimal for the recovery of Enterobacteriaceae. Therefore, it is likely that many patients colonised with multidrug-resistant Enterobacteriaceae remain undetected. The present study aimed to analyse if the detection of multidrug-resistant Enterobacteriaceae can be improved when screening with rayon swabs is done in combination with an additional pre-enrichment step. The detection of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) was assessed in 514 rectal samples by the standard diagnostic approach (direct plating of swabs on selective ESBL agar) and after pre-enrichment in 5 mL of a semi-selective MacConkey broth. The recovery rate of 3GCREB and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), patient characteristics and isolate characteristics were evaluated for both diagnostic approaches. Overall, by pre-enrichment, the detection of 3GCREB carriers increased by 22.8% (13/57, p = 0.004) and the detection of ESBL-E carriers by 21.4% (9/42, p = 0.01). This study demonstrates the low sensitivity of rectal screening by direct plating and the improvement by pre-enrichment. We believe that it is no longer acceptable to refrain from pre-enrichment as, with the standard approach, more than 20% of 3GCREB and ESBL-E carriers remain undetected

Rare-earth-size effects on thermoluminescence and second-harmonic generation

WOS: 000167639600016The substitution of rare-earth ions into insulating host crystals introduces lattice strains and, for non-trivalent sites, a need for charge compensation. Such effects alter the site symmetry and this is reflected in properties such as the wavelength, linewidth, lifetime and relative intensity of the rare-earth transitions. Equally clear, but less well documented, is the influence on second-harmonic generation (even from cubic crystal lattices). For example, in bismuth germanate, second-harmonic generation efficiency varies by factors of more than 100 as a result of different rare-earth dopant ions. The ions are variously incorporated as substitutional ions, pairs, clusters, or even as precipitates of new phases, but the detailed modelling is often speculative. This article summarizes some recent studies which explore the role of rare-earth ions in thermoluminescence and second-harmonic generation. There are numerous differences in glow peak temperature, for nominally the same defect sites, which are thought to indicate charge trapping and recombination within coupled defect sites, or within a large complex. Size and cluster effects can be modified by heat treatments. This review considers the similarity and trends seen between numerous host lattices which are doped with rare-earth ions. For thermoluminescence there are trends in the variation in glow peak temperature with ion size, with movements of 20 to 50 It. Examples are seen in many hosts with extreme effects being suggested for zircon, with peak shifts of 200 K (probably from precipitate phases)

Evaluation of the Use of Rectal Swabs for Laboratory Diagnosis of Clostridium difficile Infection

For the diagnosis of Clostridium difficile infection (CDI), microbiological testing is almost always accomplished through the analysis of stool specimens. We evaluated the performances of rectal swabs with liquid transport medium (FS) and nylon flocked dry swabs for the detection of C. difficile. Additionally, the impact on the diagnostic yield of storing swabs at -80 degrees C for up to 3 months was evaluated. Sixty clinical stool samples positive for C. difficile by PCR were used for simulating rectal swabbing. FS and dry swabs were dipped into the stool and tested by PCR directly after swabbing at 1 and 3 months after storage at -80 degrees C. Stool and the liquid medium of FS were additionally tested by a combination of glutamate dehydrogenase antigen (GDH) testing and toxin A/B enzyme immunoassay (EIA), as well as by toxigenic culture (TC). Using dry swabs, the PCR-based detection rate of C. difficile was equal to the rate using stool samples (30/3. [100%]), whereas the detection rate in FS was significantly lower (25/30 [83.2%]; P = 0.019). The sensitivities of FS for detecting C. difficile by PCR, TC, GDH testing, and toxin A/B EIA were 83.3%, 85.7%, 88%, and 68.9%, respectively. Storage of swabs at -80 degrees C had no impact on the detection rate. FS cannot replace stool samples in the two-step laboratory diagnosis of CDI, as the sensitivities were too low, probably due to diluting effects of the fecal sample in the liquid medium. For simple PCR-based detection of C. difficile, dry swabs proved to be a suitable alternative to the use of stool samples