The tubarial salivary glands:A potential new organ at risk for radiotherapy

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results. Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Micro-CT of Early Human Development

Online supplemental material is available for this article

The use of 3D-CT in weapon caused impression fractures of the skull, from a forensic radiological point of view

Objective: The aim of this study was to analyze the usefulness of the three-dimensional (3D) volume renderings (VRTs), based on computed tomography (CT) images of the head, to gain more insight in the etiology of impression skull fractures. Materials and methods: 3D-CT scans of 12 forensic cases with impression skull fractures after head injury were selected. Ten radiologists were asked to determine the shape of the used object, the amount of blows and the location of the fracture, based on 2D CT images and 3D volume renderings. Afterwards, the results of the assessments were compared with the real shapes of the true object in case. Results: In 7 out of 12 cases, the used weapon was a hammer. In 62% of the cases the shape of the used object was determined correctly by the radiologists and in 72% of the cases the amount of blows on the skull was correct. There was no significant difference in results between the forensically experienced and forensically inexperienced radiologists. Conclusion: 3D-CT is useful in a forensic setting, to determine the shape of a suspected weapon and the amount of blows. However, assessment of the CT data should always be combined with information about the scene and a profound morphological inspection of the wound

The development of the human notochord

The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man. Proper knowledge of the development of the human notochord, therefore, is important to understand the pathogenesis of these birth defects. Textbook descriptions vary significantly and seem to be derived from both human and animal data whereas the lack of references hampers verification of the presented data. Therefore, a verifiable and comprehensive description of the development of the human notochord is needed. Our analysis and three-dimensional (3D) reconstructions of 27 sectioned human embryos ranging from Carnegie Stage 8 to 15 (17-41 days of development), resulted in a comprehensive and verifiable new model of notochordal development. Subsequent to gastrulation, a transient group of cells briefly persists as the notochordal process which is incorporated into the endodermal roof of the gut while its dorsal side attaches to the developing neural tube. Then, the notochordal process embeds entirely into the endoderm, forming the epithelial notochordal plate, which remains intimately associated with the neural tube. Subsequently, the notochordal cells detach from the endoderm to form the definitive notochord, allowing the paired dorsal aortae to fuse between the notochord and the gut. We show that the formation of the notochordal process and plate proceeds in cranio-caudal direction. Moreover, in contrast to descriptions in the modern textbooks, we report that the formation of the definitive notochord in humans starts in the middle of the embryo, and proceeds in both cranial and caudal directions