Notes

Simple and easy speedy high-throughput assay to distinguish HSV-1 ICP0 transactivation inhibitors.
The SickKids Cancer Sequencing (KiCS) Program, launched in 2016, evaluates the clinical utility of paired tumor/germline Next-Generation Sequencing (NGS) in pediatric oncology patients with hard-to-cure and rare cancers. In anticipation of further widespread adoption of NGS, we aimed to characterize the experiences and perspectives of adolescents and parents of patients who have already undergone NGS evaluation, focusing on the psychosocial impact and personal utility.

Parents of patients with pediatric cancer and adolescent patients who have participated in KiCS were invited to participate in semistructured interviews. Transcripts were analyzed using an inductive content analytic approach.

Of 45 individuals invited, 22 parents and 10 adolescents were interviewed (71% response rate). Prominent psychosocial themes were low distress, relief, and sense of control; some expressed fear of the unknown. In exploring constructs of personal utility, parents highlighted hope for treatment options despite low expevalue of NGS in pediatric precision oncology care through assessment of patient-reported outcomes and experiences. These results also guide provision of pre- and post-test education and support, which will facilitate patient-centered delivery of NGS practices.The phosphatidylinositol 3-kinase (PI3K) pathway is an intracellular pathway activated in response to progrowth signaling, such as human epidermal growth factor receptor 2 (HER2) and other kinases. Abnormal activation of PI3K has long been recognized as one of the main oncogenic drivers in breast cancer, including HER2-positive (HER2+) subtype. Somatic activating mutations in the gene encoding PI3K alpha catalytic subunit (PIK3CA) are present in approximately 30% of early-stage HER2+ tumors and drive therapeutic resistance to multiple HER2-targeted agents. Here, we review currently available agents targeting PI3K, discuss their potential role in HER2+ breast cancer, and provide an overview of ongoing trials of PI3K inhibitors in HER2+ disease. Additionally, we review the landscape of PIK3CA mutational testing and highlight the gaps in knowledge that could present potential barriers in the effective application of PI3K inhibitors for treatment of HER2+ breast cancer.
Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans.

A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes.

Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recuor the first time in a human cohort.
To evaluate the performance of virtual non-contrast images (VNC) compared to true non-contrast (TNC) images in photon-counting detector computed tomography (PCD-CT) for the evaluation of lung parenchyma and emphysema quantification.

65 (mean age 73 years; 48 male) consecutive patients who underwent a three-phase (non-contrast, arterial and venous) chest/abdomen CT on a first-generation dual-source PCD-CT were retrospectively included. Scans were performed in the multienergy (QuantumPlus) mode at 120 kV with 70 ml intravenous contrast agent at an injection rate of 4 ml s
. VNC were reconstructed from the arterial (VNC
) and venous phase (VNC
). TNC and VNC images of the lung were assessed quantitatively by calculating the global noise index (GNI) and qualitatively by two independent, blinded readers (overall image quality and emphysema assessment). Emphysema quantification was performed using a commercially available software tool at a threshold of -950 HU for all data sets. TNC images served as reference standard for emphysema quantification. Low attenuation values (LAV) were compared in a Bland-Altman plot.

GNI was similar in VNC
(103.0 ± 30.1) and VNC
(98.2 ± 22.2) as compared to TNC (100.9 ± 19.0,
= 0.546 and
= 0.272, respectively). Subjective image quality (emphysema assessment and overall image quality) was highest for TNC (
= 0.001), followed by VNC
and VNC
. Both, VNC
and VNC
showed no significant difference in emphysema quantification as compared to TNC (
= 0.409 vs.
= 0.093; respectively).

Emphysema evaluation is feasible using virtual non-contrast images from PCD-CT.

Emphysema quantification is feasible and accurate using VNC images in PCD-CT. Based on these findings, additional TNC scans for emphysema quantification could be omitted in the future.
Emphysema quantification is feasible and accurate using VNC images in PCD-CT. Based on these findings, additional TNC scans for emphysema quantification could be omitted in the future.
Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model.

PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times.

The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm
. MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3%
58.0% and 3-year OS 51.5%
66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities.

A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.
A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.
The purpose is to establish and validate a machine-learning-derived radiomics approach to determine the existence of atrial fibrillation (AF) by analyzing epicardial adipose tissue (EAT) in CT images.

Patients with AF based on electrocardiographic tracing who underwent contrast-enhanced (
= 200) or non-enhanced (
= 300) chest CT scans were analyzed retrospectively. After EAT segmentation and radiomics feature extraction, the segmented EAT yielded 1691 radiomics features. The most contributive features to AF were selected by the Boruta algorithm and machine-learning-based random forest algorithm, and combined to construct a radiomics signature (EAT-score). Multivariate logistic regression was used to build clinical factor and nested models.

In the test cohort of contrast-enhanced scanning (
= 60/200), the AUC of EAT-score for identifying patients with AF was 0.92 (95%CI 0.84-1.00), higher than 0.71 (0.58-0.85) of the clinical factor model (total cholesterol and body mass index) (DeLong's
= 0.01), and higher than 0.73 (0.61-0.86) of the EAT volume model (
= 0.01). In the test cohort of non-enhanced scanning (
= 100/300), the AUC of EAT-score was 0.85 (0.77-0.92), higher than that of the CT attenuation model (
< 0.001). The two nested models (EAT-score+volume and EAT-score+volume+clinical factors) for contrast-enhanced scan and one (EAT-score+CT attenuation) for non-enhanced scan showed similar AUCs with that of EAT-score (all
> 0.05).

EAT-score generated by machine-learning-based radiomics achieved high performance in identifying patients with AF.

A radiomics analysis based on machine learning allows for the identification of AF on the EAT in contrast-enhanced and non-enhanced chest CT.
A radiomics analysis based on machine learning allows for the identification of AF on the EAT in contrast-enhanced and non-enhanced chest CT.
Several pre-operative parameters have been studied to estimate stone-free rate (SFR) following retrograde intrarenal surgery (RIRS) procedures. The objective of this study was to evaluate the effects of stone density on surgical outcomes of RIRS.

This retrospective study included 30 stone-free patients (Group SF) and 30 patients with residual fragments (Group RF). Patients' age and gender, laterality, non-contrast CT findings, including size and density of the kidney stones, infundibular pelvic angle (IPA), operational time, and post-operative pain were recorded and compared between the two groups. The stone density was measured by free hand region of interest (ROI) determination coincident with the stone borders and expressed as Hounsfield units (HUs).

The rate of single stones was significantly higher in Group SF compared to Group RF (
< 0.001). The mean stone size was found as 11.93 ± 7.81 mm in Group SF and 16.27 ± 7.29 mm in Group RF with the difference being statistically significant (
< 0.001). The mean IPA was 53.87 degrees in Group SF and 50.33 degrees in Group RF. The mean density was measured as 748.17 ± 318.14 HU in Group SF and 945.90 ± 345.30 HU in Group RF. The mean stone density was statistically significantly higher in patients with residual fragments compared to the stone-free patients (
< 0.001).

This study revealed that stone density as measured as HU affects the treatment outcomes with RIRS procedure and the mean density is significantly higher in patients with residual stone fragments.

Studies about the effects of HUs on stone-free rate are limited in the literature. Stone density affects the treatment outcomes with RIRS procedure and the mean density is significantly higher in patients with residual stone fragments.
Studies about the effects of HUs on stone-free rate are limited in the literature. Stone density affects the treatment outcomes with RIRS procedure and the mean density is significantly higher in patients with residual stone fragments.Given the ever-increasing utilization of magnetic resonance angiography, incidental vascular findings are increasingly discovered on exams performed for unconnected indications. click here Some incidental lesions represent pathology and require further intervention and surveillance, such as aneurysm, certain vascular malformations, and arterial stenoses or occlusions. Others are benign or represent normal anatomic variation, and may warrant description, but not further work-up. This review describes the most commonly encountered incidental findings on magnetic resonance angiography, their prevalence, clinical implications, and any available management recommendations.
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