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Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.  相似文献   
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Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely...  相似文献   
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Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

Materials and Methods

Data were collected from 336 patients undergoing PN for suspected renal cancer by 40 surgeons at 12 centers in Europe and the United States within the Surface-Intermediate-Base International Consortium. Surgeons recorded PAVP and SAVP for individual patients; pre- and postoperative glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equations. Correlations between PAVP, SAVP, and postoperative GFR were assessed with linear regression models. Bland–Altman analysis was used to assess agreement between PAVP and SAVP with a significant cutoff of 5%.

Results

Median PAVP was 90% (interquartile range [IQR] 85%–100%) and SAVP was 90% (IQR: 80%–94%). PAVP and SAVP were moderately correlated (R2?=?0.67, P < 0.0001) and deemed “interchangeable” by Bland–Altman analysis at a 5% acceptable rate of difference (95% CI: ?5.4, ?3.1). Median postoperative GFR was 77.3 (IQR: 56.2, 92.0). Both PAVP (R2?=?0.82, P < 0.0001) and SAVP (R2?=?0.83, P < 0.0001) were correlated with postoperative GFR. Multivariable models utilizing volume-adjusted GFR based on PAVP or SAVP significantly and similarly predicted postoperative GFR (R2?=?0.72 for each).

Conclusion

Renal function is closely linked to the amount of parenchymal volume preservation, whether estimated prior to surgery (PAVP) or afterward (SAVP). PAVP provides reasonably accurate information for decision-making in patients considering PN.  相似文献   
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The processes involved in value evaluation and self‐control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision‐making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice‐decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self‐control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity‐related brain disorders.  相似文献   
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Background

There is a lack of studies addressing the occurrence of negative intraoperative findings (that is the absence of intussusception) after an unsuccessful hydrostatic reduction of an ileocolic intussusception. The aim of this study is to determine the incidence of negative intraoperative findings after unsuccessful hydrostatic reduction of ileocolic intussusception.

Methods

We conducted a multicentre retrospective study of all children aged 0–18?years treated for ileocolic intussusception from January 1, 2010 to December 31, 2015 in 9 Dutch hospitals. Primary outcome measure was the percentage of children without an intussusception during surgical exploration after unsuccessful hydrostatic reduction.

Results

In the study period 436 patients were diagnosed with an ileocolic intussusception. Of these, 408 patients underwent hydrostatic reduction of an ileocolic intussusception. 112 patients (27.5%) underwent surgery after an unsuccessful hydrostatic reduction. In 13 (11.6%) patients no intraoperative evidence of intussusception was found. Patients who underwent surgical intervention after unsuccessful hydrostatic reduction were significantly younger than patients who had a successful hydrostatic reduction; there was no gender difference.

Conclusion

A substantial number of children (11.6%) underwent a laparotomy after unsuccessful hydrostatic reduction in whom no intussusception was found intraoperatively. We suggest initiating laparoscopy instead of laparotomy when surgery is necessary.

Level of evidence

Level II.  相似文献   
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Objective

Medical devices (MDs) encompass a broad and heterogeneous range of technologies. While practices vary considerably across countries, MDs often find application in patient care with little or no evaluation of their effectiveness and safety following market approval. A recently proposed taxonomy of MDs considered devices from the viewpoint of Health Technology Assessment (HTA). The aim of the work presented here was to test its plausibility and applicability by considering real-world HTA practices.

Methods

HTA reports on MDs from European institutions were collected in a systematic manner and the evaluated devices and/or related procedures were matched to a position on the taxonomy. Following this, representatives from 16 European HTA institutions were asked about the usefulness of the taxonomy in semi-structured interviews.

Results

1237 HTA reports (2004–2015) from 33 European institutions were included in the sample. The majority of reports was on technologies from the taxonomic positions initially estimated as having high relevance. Most of the experts interviewed stated that they found the taxonomy useful, particularly regarding its potential to aid in selecting technologies for assessment and to highlight potential methodological particularities per taxonomic position.

Conclusions

Overall, the distribution of identified reports on the matrix confirmed that the initial estimation of the relevance and necessity of HTA provided in the taxonomic model is plausible. In addition, interviews with representatives of European HTA institutions showed that the taxonomy could be useful.  相似文献   
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