Biomarkers for Serious Bacterial Infections in Febrile Children.

Febrile infections in children are a common cause of presentation to the emergency department (ED). While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; nowadays, a better understanding of immunochemical pathways has led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models, combining them for serious bacterial infection (SBI) diagnosis in febrile children. Literature analysis shows that inflammatory response is a complex mechanism in which many biochemical and immunological factors contribute to the host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined, and for this reason, it is reasonable to take them both into consideration in the evaluation of febrile children. The potential of machine learning tools, which represent a real novelty in medical practice, in conjunction with routine clinical and biological information, may improve the accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pediatric precision medicine still uncertain. More data from further research are needed to improve clinical practice and decision making using these new technologies.

Case Report: short stature, kidney anomalies, and cerebral aneurysms in a novel homozygous mutation in the PCNT gene associated with microcephalic osteodysplastic primordial dwarfism type II.

We report the case of a boy (aged 3 years and 7 months) with severe growth failure (length: -9.53 SDS; weight: -9.36 SDS), microcephaly, intellectual disability, distinctive craniofacial features, multiple skeletal anomalies, micropenis, cryptorchidism, generalized hypotonia, and tendon retraction. Abdominal US showed bilateral increased echogenicity of the kidneys, with poor corticomedullary differentiation, and a slightly enlarged liver with diffuse irregular echotexture. Initial MRI of the brain, performed at presentation, showed areas of gliosis with encephalomalacia and diffused hypo/delayed myelination, and a thinned appearance of the middle and anterior cerebral arteries. Genetic analysis evidenced a novel homozygous pathogenic variant of the pericentrin (PCNT) gene. PCNT is a structural protein expressed in the centrosome that plays a role in anchoring of protein complexes, regulation of the mitotic cycle, and cell proliferation. Loss-of-function variants of this gene are responsible for microcephalic osteodysplastic primordial dwarfism type II (MOPDII), a rare inherited autosomal recessive disorder. The boy died at 8 years of age as a result of an intracranial hemorrhage due to a cerebral aneurism associated with the Moyamoya malformation. In confirmation of previously published results, intracranial anomalies and kidney findings were evidenced very early in life. For this reason, we suggest including MRI of the brain with angiography as soon as possible after diagnosis in follow-up of MODPII, in order to identify and prevent complications related to vascular anomalies and multiorgan failure.

Comprehensive Analysis of Radiomic Datasets by RadAR.

Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition, segmentation, feature extraction, and analysis of high-dimensional datasets. While procedures for primary radiomic analyses have been established in recent years, processing the resulting radiomic datasets remains a challenge due to the lack of specific tools for doing so. Here we present RadAR (Radiomics Analysis with R), a new software to perform comprehensive analysis of radiomic features. RadAR allows users to process radiomic datasets in their entirety, from data import to feature processing and visualization, and implements multiple statistical methods for analysis of these data. We used RadAR to analyze the radiomic profiles of more than 850 patients with cancer from publicly available datasets and showed that it was able to recapitulate expected results. These results demonstrate RadAR as a reliable and valuable tool for the radiomics community. SIGNIFICANCE: A new computational tool performs comprehensive analysis of high-dimensional radiomic datasets, recapitulating expected results in the analysis of radiomic profiles of >850 patients with cancer from independent datasets.

Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts.

Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.

Commissioning Varian enhanced dynamic wedge in the PINNACLE treatment planning system using Gafchromic EBT film.

In external photon beam therapies, the technique of dynamic wedge is a well established method for dose inhomogeneity compensation. The introduction of the enhanced dynamic wedge (EDW) on Varian LINACs considerably improved the pre-existing techniques. In the process of commissioning a Varian LINAC into a PINNACLE3 treatment planning system (TPS), the user is required to import quite a few measurements of EDW profiles and percentage depth doses (PDDs). Standard measurement devices like ionization chambers in a water phantom are not the most indicated ones for this situation where each measurement point is obtained by integrating during the entire exposure: Measurements would result to be a very laborious and time consuming operation, most of the times not practically possible. The goal of the present work is to introduce an alternative and hands-on procedure to perform the measurements using a combination of GafchromicTM EBT films, irradiated sideways in one single shot for both profiles and PDDs, and a single standard ionization chamber. The scanned profiles obtained at different depths have easily been imported in the TPS; for the PDD measurements, a correction was proven necessary to account for a "self-shielding" effect introduced by the presence of the films themselves, when irradiated sideways, resulting in an underestimation of the dose at deeper depths. A correction curve was derived comparing TPS open field validated measurements with the curves extracted from GafchromicTM EBT films. Finally, the curve was applied to all the wedged fields PDD measurements and could minimize the errors. The comparison for the 15 MV photon beam between the measured and the calculated 48 profiles and 12 PDDs (field sizes from 5 x 5 to 20 x 20 cm2, wedge angles ranging from 15 degrees to 60 degrees) was acceptable. The confidence limit (CL) was used as fit indicator, as suggested by the ESTRO Booklet No. 7: For the investigated PDDs the maximum value was 6.40 in the build up region and 2.83 beyond the maximum dose point; regarding cross beam profiles, the CLs were below 3 for 85% of the points within the field and for 96% of the points outside the field; in the penumbra region, a more appropriate parameter to evaluate the agreement between calculated and measured doses is the distance to agreement; only 73% of the profiles had CLs below 15, but for the remaining ones, distance-to-agreement values were within 3 mm. A hundred ionization chamber point dose measurements (for square and elongated fields at different depth and for points in field and out of field) were performed in a water phantom and 98 of them confirmed the TPS calculations with differences lower than 3% and considerably lower in most of the cases. This article gives valuable guidance and insight to other physicists attempting to approach EDW commissioning in the PINNACLE TPS software using Gafchromic EBT films.