Upper Tract Imaging in Patients with Initial or Terminal Hematuria Suggestive of Bleeding from the Lower Urinary Tract: How Often is the Upper Urinary Tract Responsible for the Hematuria?

Objectives: Visible hematuria (VH) is a common urological complaint. A history of initial or terminal VH in men is indicative of a lower urinary tract (LUT) source. A careful clinical history could limit unnecessary extensive upper tract imaging in this group of patients with VH. We conducted a single-center prospective study to examine the usefulness of investigating the upper tract in patients with a history of VH likely from a LUT source (initial and/or terminal VH) with specific reference to the incidence of demonstrable significant upper tract abnormalities. Methods: We conducted a single-center prospective study of consecutive male patients presenting with VH over eight months. All patients underwent standard investigations including physical examination, flexible cystoscopy (FC), and radiological imaging (ultrasound scan (USS) and/or computed tomography urogram (CTU)). Those with a clear history of initial or terminal VH were identified for further scrutiny with regards to detectable upper tracts abnormalities. Results: In total, 57 patients (aged 23–95 years) with initial or terminal VH were identified. Of these, 56 had FC and nine patients were subsequently diagnosed with a LUT malignancy. With regards to upper urinary tract (UUT), 35 patients (61.4%) had an USS, 46 (80.7%) underwent a CTU, and 25 (43.9%) patients had both. In this group, no UUT malignancy was identified on upper tract imaging. Conclusions: Initial or terminal VH patients may not need extensive upper tract imaging. FC is recommended, but a non-invasive USS can be a safe initial investigation for the UUT, with a CTU subsequently considered in those with abnormalities on USS and those with ongoing bleeding. Further combined multicenter analysis will help corroborate these findings and could have several beneficial outcomes including a reduction in investigations cost, patient inconvenience, and ionizing radiation

Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19

Background While inflammatory and immune responses to SARS-CoV-2 infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished COVID-19 severity categories, and relate these to disease progression and peripheral inflammation. Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalised with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days post-symptom onset) or late (6-20 days post-symptom onset). Results Patients that survived severe COVID-19 showed IFN-dominated mucosal immune responses (IFN-γ, CXCL10 and CXCL13) early in infection. These early mucosal responses were absent in patients that would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by IL-2, IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions Defective early mucosal anti-viral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Design and analysis of optical flow-switched networks

In our previous work [Chan, “Optical flow switching,” in BROADNETS 2006, pp. 1-8; Weichenberg, “Cost-efficient optical network architectures,” in ECOC 2006, pp. 1-2; Weichenberg, “On the throughput-cost tradeoff of multi-tiered optical network architectures,” GLOBECOM '06, pp. 1-6], we presented optical flow switching (OFS) as a key enabler of scalable future optical networks. We now address the design and analysis of OFS networks in a more comprehensive fashion. The contributions of this work, in particular, are in providing partial answers to the questions of how OFS networks can be implemented, how well they perform, and how their economics compare with those of other architectures. With respect to implementation, we present a sensible scheduling algorithm for inter-metropolitan-area-network (inter-MAN) OFS communication. Our performance study builds upon our work in IEEE J. Sel. Areas Commun., vol. 25, no. 6, pp. 84-101, 2007 and Weichenberg, “Performance analysis of optical flow switching,” presented at the IEEE International Conference on Communications, Dresden, Germany, June 14-18, 2009, and includes a comparative capacity analysis for the wide area, as well as an analytical approximation of the throughput-delay trade-off offered by OFS for inter-MAN communication. Last, with regard to the economics of OFS, we extend our previous work from ECOC 2006 and GLOBECOM '06 in carrying out an optimized throughput-cost comparison of OFS with other prominent candidate architectures. Our conclusions indicate that OFS offers a significant advantage over other architectures in economic scalability. In particular, for sufficiently heavy traffic, OFS handles large transactions at far lower cost than other optical network architectures. In light of the increasing importance of large transactions to communication networks, we conclude that OFS may be crucial to the future viability of optical networking