Quantitative Torque Teno Virus Plasma DNA Assessments May Complement Donor-Derived Cell-Free DNA for Detection of Immunologic Events after Lung Transplantation

Torque Teno Virus (TTV) of the genus Anelloviridae , is an unenveloped, circular DNA virus with 23 genotypes that has been shown to be a potential surrogate biomarker for "Net State of Immunosuppression" in organ transplantation. Additionally, TTV levels have been shown to correlate with acute rejection (AR) and chronic lung allograft dysfunction (CLAD) as well as response to CoVid-19 vaccine in lung transplantation. Donor-derived cell-free DNA (dd-cfDNA) is a validated biomarker known to detect AR, CLAD and infection in lung transplant (LT) patients. We hypothesize that plasma TTV levels may complement dd-cfDNA in detecting different immunologic events after LT. We prospectively collected plasma samples from LT recipients from a single center LT program. dd-cfDNA was analyzed and clinical-pathologic events were carefully adjudicated and curated in all lung transplant recipients to define AR, CLAD, infection and stable samples. Herein, we analyze these plasma samples by Next Generation Sequencing (NGS) with quantification for TTV. Analyses will examine time-dependent performance characteristics of both dd-cfDNA fraction and quantified TTV levels for the endpoints AR, CLAD and infection with stable samples used as the comparison group. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Three cases of spontaneous major bleeding in patients with a COVID-19 infection.

In addition to the respiratory compromise typical for COVID-19 many papers reported on the thromboembolic complications in these often critically ill patients. In this report, three cases of patients that developed spontaneous major bleeding following treatment with therapeutic anticoagulation for thromboembolic complications of COVID-19 were described. Two cases were treated with coil-embolization and one patient could be treated conservatively. These cases illustrate the presence of a relevant bleeding risk against the background of the well-known thromboembolic complications associated with COVID-19. The increased risks of thromboembolic complications in COVID-19 warrant adequate prophylactic anticoagulation. The optimal dose to obtain a significant risk reduction without a significant increase in the incidence of major bleeding requires further research.

Perceptions on the Use of an Online Tool in the Teaching-learning Process in Microscopy

During the COVID-19 pandemic, remote learning was an alternative to maintaining student participation in subjects, active learning, and knowledge development. This approach is necessary for the experimental demands of the practical content of the Cervical Cytology class. This paper presents and discusses using an online platform to learn practical content in the microscopy subject of Cervical Cytology class. The evaluated scenarios demonstrated that the planning of the discipline and personal factors such as student interest and availability could influence the student performance. Copyright © 2022 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved.

Improvements in Quality of Life at 1 Year in Patients Treated with Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: An Interim Analysis of Clarify-MS

Background: Multiple sclerosis (MS) is a chronic disabling disease associated with negative effects on quality of life (QoL), including physical and mental health. The objective of this investigation was to evaluate the change in QoL for patients with highly active relapsing MS at 1 year after initiating treatment with cladribine tablets (CladT), by assessing changes in the physical and mental health composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54). Material(s) and Method(s): In CLARIFY-MS (NCT03369665), patients with highly active relapsing MS were assigned to receive CladT 3.5 mg/kg cumulative dose over 2 years. Patients were recruited as per the EU label. Results in this interim analysis, conducted prior to the second year of treatment, were assessed using a mixed-effects linear model. Analyses were also conducted for cohorts separated by treatment naïve/prior disease-modifying therapy (DMT), and MSQoL reporting performed before/after the start of the COVID-19 pandemic, as defined as the first reported fatality within each country. Result(s): Of the 482 patients treated with CladT, 70.1% were female and the mean age was 37.4 years. Of the 426 patients who provided MSQoL-54 data, statistically significant (p<0.0001) improvements from Baseline to Month 12 were observed for physical and mental health composite scores with estimated changes of 4.51 (95% confidence interval [CI] 3.24–5.77) and 4.53 (95% CI 3.00–6.05), respectively. Similar trends were apparent for treatment naïve (n=121) and prior DMT (n=305) cohorts. There was no indication that the start of the COVID-19 pandemic had an impact on MSQoL-54 reporting. Regarding safety, 322 patients (66.8%) experienced at least one treatment-emergent adverse event, most commonly headache (16%), nasopharyngitis (9%), and lymphopenia (9%). The majority of observed post-baseline lymphopenia events were grade 1–2;fewer patients reported grade 3 lymphopenia, no grade 4 lymphopenia was observed. Conclusion(s): With only half a therapeutic dose of CladT, this interim analysis demonstrates a statistically significant improvement in the physical and mental health composite scores of MSQoL-54 at 1 year. No new safety concerns were found in this 1-year interim analysis, with no new severe or opportunistic infections that could have an impact on the established benefit:risk profile of CladT in MS.

A North American Collaboration Integrating Digital Pathology into Residency Curriculum: Steps towards Global Training in the Digital Age

Background: Digital pathology is emerging as a critical tool in daily practice as highlighted by the SARS-CoV-2 pandemic. Pathology residents must gain adequate exposure to this technology as they approach independent practice. In this feasibility study, Canadian residents worked remotely with a United States (US)-based laboratory to help them prepare for careers in the digital age. Design: As part of their Canadian-based genitourinary (GU) pathology rotation, three 3rd-year Anatomical Pathology residents engaged in longitudinal screening and drafting of reports for digitally scanned US-based prostate biopsy cases prepared by a US laboratory specializing in digital pathology technology. Each trainee screened routine US-based digital case work as part of their curriculum and had access to artificial intelligence (AI) diagnostic software (Figure 1) during their case analyses. Residents also completed a digital pre- and post-test to assess diagnostic accuracy and time spent per core. Neither AI nor immunostains were permitted during the pre- and post-test sessions. Diagnoses were considered correct when no major discrepancies existed between resident and approved report. Results: Residents each screened and reported 10 digital prostate biopsy cases in addition to routine GU workload (Table 1). The digital pathology software allowed trainees to annotate specific histologic features and leave notes as required which could be subsequently reviewed remotely by supervisors. Feedback was provided by three anatomical pathologists, one practicing at the residents' home institution and the other two practicing at the US-based laboratory. Sign out session format varied but included video meetings with screen sharing, text messaging, phone calls, and/or email messages. Residents scored 76.67% (SD 5.7%) on the pre-test and 96.67% (SD 5.7%) on the post-test with respect to diagnostic accuracy;the average time per core decreased over the course of the rotation (Table 1). Conclusions: In this feasibility study, Canadian residents used a US-based digital pathology platform to remotely preview routine prostate biopsy casework. The residents gained exposure to digital pathology technology, including AI. Over the course of their rotations, all residents improved. These findings provide a framework for future global pathology education outreach.