Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry

OBJECTIVE: To characterize the association of pleuropulmonary blastoma (PPB) with cystic nephroma (CN) and other renal tumors. STUDY DESIGN: Complete clinicopathologic review of cases from the International PPB Registry and literature. RESULTS: We identified 18 patients with PPB associated with 20 renal tumors (15 CN), either in themselves or family members. All patients with PPB were <5 years of age. All but one of the renal diagnoses were made before 4 years of age. Eleven children had both PPB and renal tumor, one of whom also had a sibling with CN. Six children with PPB alone had one or more family members with CN. The mother of one child with PPB had Wilms' tumor. Pulmonary disease was bilateral in four patients. Renal disease was bilateral in three patients. Two children with PPB and bilateral renal cystic tumors also had intussusceptions because of small bowel juvenile polyps. In six families, dysplasia/neoplasia affected organs other than lung and kidney. CONCLUSIONS: CN or related tumors were found in 9.2% of 152 Registry-reviewed PPB cases. The occurrence of rare pulmonary and renal tumors together in patients and/or family members, the early age of onset, and the multiplicity of tumors is compatible with a constitutional genetic predisposition.     

Interleukin-1 Is Overexpressed in Injured Muscles Following Spinal Cord Injury and Promotes Neurogenic Heterotopic Ossification

Neurogenic heterotopic ossifications (NHOs) form in periarticular muscles after severe spinal cord (SCI) and traumatic brain injuries. The pathogenesis of NHO is poorly understood with no effective preventive treatment. The only curative treatment remains surgical resection of pathological NHOs. In a mouse model of SCI-induced NHO that involves a transection of the spinal cord combined with a muscle injury, a differential gene expression analysis revealed that genes involved in inflammation such as interleukin-1β (IL-1β) were overexpressed in muscles developing NHO. Using mice knocked-out for the gene encoding IL-1 receptor (IL1R1) and neutralizing antibodies for IL-1α and IL-1β, we show that IL-1 signaling contributes to NHO development after SCI in mice. Interestingly, other proteins involved in inflammation that were also overexpressed in muscles developing NHO, such as colony-stimulating factor-1, tumor necrosis factor, or C-C chemokine ligand-2, did not promote NHO development. Finally, using NHO biopsies from SCI and TBI patients, we show that IL-1β is expressed by CD68⁺ macrophages. IL-1α and IL-1β produced by activated human monocytes promote calcium mineralization and RUNX2 expression in fibro-adipogenic progenitors isolated from muscles surrounding NHOs. Altogether, these data suggest that interleukin-1 promotes NHO development in both humans and mice. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Patterns of locoregional failure in locally advanced non-small cell lung cancer treated with definitive conformal radiotherapy: Results from the Gating 2006 trial

Purpose

To determine the patterns of locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy (RT).

Self-reflection across time: cortical midline structures differentiate between present and past selves

The processing of personal changes across time and the ability to differentiate between representations of present and past selves are crucial for developing a mature sense of identity. In this study, we explored the neural correlates of self-reflection across time using functional magnetic resonance imaging (fMRI). College undergraduates were asked to reflect on their own psychological characteristics and those of an intimate other, for both the present time period (i.e. at college) and a past time period (i.e. high school years) that involved significant personal changes. Cortical midline structures (CMS) were commonly recruited by the four reflective tasks (reflecting on the present self, past self, present other and past other), relative to a control condition (making valence judgments). More importantly, however, the degree of activity in CMS also varied significantly according to the target of reflection, with the ventral and dorsal medial prefrontal cortex and the posterior cingulate cortex being more recruited when reflecting on the present self than when reflecting on the past self or when reflecting on the other person. These findings suggest that CMS may contribute to differentiate between representations of present and past selves.     

Candiduria in kidney transplant recipients: Is antifungal therapy useful?

A French single‐centre retrospective study between 2010 and 2014 was undertaken to assess candiduria's incidence in kidney transplant recipients (KTR), and the use and impact of antifungal treatment on outcome. Candiduria was defined as a urine culture with ≥10³ cfu/mL of Candida species. Candiduria clearance, severe complications and death rates were estimated by Kaplan‐Meier methods and the effect of treatment by Cox models. 52/1223 (4.3%) KTR had ≥1 episode of candiduria, 42 (81%) were females, 18 (35%) had diabetes, with an incidence of 2.3/100 person‐year of follow‐up. Candiduria was asymptomatic in 51 (98%) patients. Candida glabrata was the most frequent pathogen identified. Overall fungal clearance rate was 89%. Antifungal therapy was initiated in only 14 episodes (12%), according to guidelines. Three patients (6%) developed severe complications in the first 2 weeks after transplantation, and 8 (15%) died. Antifungal treatment had no impact on candiduria clearance (HR, 0.6; 95% CI, 0.3‐1.1; P = .10), on recurrence rate (HR, 0.5; 95% CI, 0.1‐2.3; P = .41) and on the risk of severe complications or death (HR, 1.1; 95% CI, 0.3‐4.8; P = .89). Candiduria is rare and usually asymptomatic among KTR. Candiduria management in the immediate post‐transplant period deserves careful attention.     

Expression and secretion of alpha1-proteinase inhibitor are regulated by proinflammatory cytokines in human pancreatic islet cells

Aims/hypothesis Alpha1-proteinase inhibitor (1-PI) has been considered a key player in inflammatory processes. In humans, the main production site of 1-PI is the liver, but other tissues, including pancreatic islets, also synthesise this molecule. The aims of this study were to assess the islet cell types that produce 1-PI, to determine whether 1-PI is actually secreted by islet cells, and to assess how its production and/or secretion are regulated.Methods Expression of 1-PI in human islet cells was assessed by immunofluorescence, electron microscopy and western blotting. Release of 1-PI was analysed by reverse haemolytic plaque assay and ELISA. The effects of cytokines on 1-PI synthesis and secretion were tested.Results Immunofluorescence showed that alpha and delta cells do express 1-PI, whereas beta cells do not. By electron microscopy, we demonstrated a colocalisation of 1-PI with glucagon and somatostatin within secretory granules. Immunolabelling also revealed localisation of 1-PI within the Golgi apparatus, related vesicles and lysosomal structures. The expression of 1-PI in islet cells was also demonstrated by western blotting and ELISA of protein extracts. ELISA and reverse haemolytic plaque assay showed that 1-PI is secreted into the culture medium. Treatment of islet cells with IL-1 and oncostatin M for 4 days increased the production and release of 1-PI.Conclusions/interpretation Our results demonstrate that 1-PI is expressed by the alpha and delta cells of human islets, and that proinflammatory cytokines enhance the production and release of this inhibitor.