Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is characterized by severe pneumonia and/or acute respiratory distress syndrome in about 20% of infected patients. Computed tomography (CT) is the routine imaging technique for diagnosis and monitoring of COVID-19 pneumonia. Chest CT has high sensitivity for diagnosis of COVID-19, but is not universally available, requires an infected or unstable patient to be moved to the radiology unit with potential exposure of several people, necessitates proper sanification of the CT room after use and is underutilized in children and pregnant women because of concerns over radiation exposure. The increasing frequency of confirmed COVID-19 cases is striking, and new sensitive diagnostic tools are needed to guide clinical practice. Lung ultrasound (LUS) is an emerging non-invasive bedside technique that is used to diagnose interstitial lung syndrome through evaluation and quantitation of the number of B-lines, pleural irregularities and nodules or consolidations. In patients with COVID-19 pneumonia, LUS reveals a typical pattern of diffuse interstitial lung syndrome, characterized by multiple or confluent bilateral B-lines with spared areas, thickening of the pleural line with pleural line irregularity and peripheral consolidations. LUS has been found to be a promising tool for the diagnosis of COVID-19 pneumonia, and LUS findings correlate fairly with those of chest CT scan. Compared with CT, LUS has several other advantages, such as lack of exposure to radiation, bedside repeatability during follow-up, low cost and easier application in low-resource settings. Consequently, LUS may decrease utilization of conventional diagnostic imaging resources (CT scan and chest X-ray). LUS may help in early diagnosis, therapeutic decisions and follow-up monitoring of COVID-19 pneumonia, particularly in the critical care setting and in pregnant women, children and patients in areas with high rates of community transmission.

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.

Background and objectivesNephrotic syndrome is a typical presentation of genetic podocytopathies but occasionally other genetic nephropathies can present as clinically indistinguishable phenocopies. We hypothesized that extended genetic testing followed by reverse phenotyping would increase the diagnostic rate for these patients.Design, setting, participants, & measurementsAll patients diagnosed with nephrotic syndrome and referred to our center between 2000 and 2018 were assessed in this retrospective study. When indicated, whole-exome sequencing and in silico filtering of 298 genes related to CKD were combined with subsequent reverse phenotyping in patients and families. Pathogenic variants were defined according to current guidelines of the American College of Medical Genetics.ResultsA total of 111 patients (64 steroid-resistant and 47 steroid-sensitive) were included in the study. Not a single pathogenic variant was detected in the steroid-sensitive group. Overall, 30% (19 out of 64) of steroid-resistant patients had pathogenic variants in podocytopathy genes, whereas a substantial number of variants were identified in other genes, not commonly associated with isolated nephrotic syndrome. Reverse phenotyping, on the basis of a personalized diagnostic workflow, permitted to identify previously unrecognized clinical signs of an unexpected underlying genetic nephropathy in a further 28% (18 out of 64) of patients. These patients showed similar multidrug resistance, but different long-term outcome, when compared with genetic podocytopathies.ConclusionsReverse phenotyping increased the diagnostic accuracy in patients referred with the diagnosis of steroid-resistant nephrotic syndrome.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort.

This paper presents a novel method for line restoration in speckle images. We address this as a sparse estimation problem using both convex and non-convex optimization techniques based on the Radon transform and sparsity regularization. This breaks into subproblems, which are solved using the alternating direction method of multipliers, thereby achieving line detection and deconvolution simultaneously. We include an additional deblurring step in the Radon domain via a total variation blind deconvolution to enhance line visualization and to improve line recognition. We evaluate our approach on a real clinical application: the identification of B-lines in lung ultrasound images. Thus, an automatic B-line identification method is proposed, using a simple local maxima technique in the Radon transform domain, associated with known clinical definitions of line artefacts. Using all initially detected lines as a starting point, our approach then differentiates between B-lines and other lines of no clinical significance, including Z-lines and A-lines. We evaluated our techniques using as ground truth lines identified visually by clinical experts. The proposed approach achieves the best B-line detection performance as measured by the F score when a non-convex \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\ell _{\text {p}}$ \end{document} regularization is employed for both line detection and deconvolution. The F scores as well as the receiver operating characteristic (ROC) curves show that the proposed approach outperforms the state-of-the-art methods with improvements in B-line detection performance of 54%, 40%, and 33% for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\text {F}}_{0.5}$ \end{document}, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\text {F}}_{1}$ \end{document}, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${\text {F}}_{2}$ \end{document}, respectively, and of 24% based on ROC curve evaluations.

Background and objectives Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV.

BackgroundLung ultrasound is a novel technique for detecting generalized fluid overload in children and adults with end-stage renal disease (ESRD). Echocardiography and bioimpedance spectroscopy are established methods, albeit variably adopted in clinical practice. We compared the practicality and accuracy of lung ultrasound with current objective techniques for detecting fluid overload in children with ESRD.MethodsA prospective observational study was performed to compare lung ultrasound B-lines, echocardiographic measurement of inferior vena cava parameters and bioimpedance spectroscopy in the assessment of fluid overload in children with ESRD on dialysis. The utility of each technique in predicting fluid overload, based on short-term weight gain, was assessed. Multiple linear regression models to predict fluid overload by weight were explored.ResultsA total of 22 fluid assessments were performed in 13 children (8 on peritoneal dialysis, 5 on haemodialysis) with a median age of 4.0 (range 0.8–14.0) years. A significant linear correlation was observed between the number of B-lines detected by lung ultrasound and fluid overload by weight (r = 0.57, p = 0.005). A non-significant positive linear correlation was observed between fluid overload by weight and bioimpedance spectroscopy (r = 0.43, p = 0.2), systolic blood pressure (r = 0.19, p = 0.4) and physical examination measurements (r = 0.19, p = 0.4), while a non-significant negative linear relationship was found between the inferior vena cava collapsibility index and fluid overload by weight (r = −0.24, p = 0.3). In multiple linear regression models, a combination of three fluid parameters, namely lung ultrasound B-lines, clinical examination and systolic blood pressure, best predicted fluid overload (R 2 = 0.46, p = 0.05).ConclusionsLung ultrasound may be superior to echocardiographic methods and bioimpedance spectroscopy in detecting volume overload in children with ESRD. Given the practicality and sensitivity of this new technique, it can be adopted alongside clinical examination and blood pressure in the routine assessment of fluid status in children with ESRD.

Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited.