Πέμπτη 18 Αυγούστου 2022

Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients

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Abstract

Background

Development of cytomegalovirus (CMV) and BK polyoma virus (BKV) infection following kidney transplantation have been associated with allograft dysfunction and allograft loss. Reduction in immunosuppression is a mainstay of management yet has been associated with increased risk of rejection. According to international consensus guidelines, one approach to management of these viral infections is to discontinue the antimetabolite. Little is known surrounding long-term outcomes in these patients, and it remains unclear if consideration should be given to resuming the antimetabolite as variable re-escalation strategies have been reported. The objective was to describe episodes of rejection and identify risk factors for rejection following antimetabolite withdrawal after CMV or BKV DNAemia in kidney transplant recipients.

Methods

This single-center, retrospective review evaluated adult kidney transplant recipients with a serum CMV or BKV DNA PCR ≥ 500 copies/mL who underwent antimetabolite discontinuation. The primary outcome assessed was the incidence of biopsy-proven acute rejection (BPAR).

Results

159 patients were included. Overall, 14 patients (8.8%) experienced BPAR at a median of 1.6 years after antimetabolite discontinuation. Compared to CMV, discontinuation after BKV DNAemia was associated with a higher incidence of BPAR. Characteristics observed more frequently in patients with BPAR included younger age, female sex, higher initial viral load, and development of de novo donor-specific antibody (DSA).

Conclusion

These findings suggest that antimetabolite discontinuation after CMV or BKV DNAemia in kidney transplant recipients is a reasonable and safe approach. Further prospective studies investigating optimal immunosuppression management following CMV or BKV DNAemia in kidney transplant recipients are warranted.

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Τετάρτη 17 Αυγούστου 2022

Novel mutations in antiviral multiresistant HSV‐2 genital lesion: a case report

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ABSTRACT

Introduction

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management.

Objective

To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion.

Results

Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still prese nt, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage.

Conclusions

This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

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Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE

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Publication date: Available online 17 August 2022

Source: Annals of Diagnostic Pathology

Author(s): Elizabeth Arslanian, Kamaljeet Singh, Katrine Hansen, M. Ruhul Quddus

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Τρίτη 16 Αυγούστου 2022

An overview of three‐dimensional imaging devices in dentistry

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Abstract

Objective

To review four types of three-dimensional imaging devices: intraoral scanners, extraoral scanners, cone-beam computed tomography (CBCT), and facial scanners, in terms of their development, technologies, advantages, disadvantages, accuracy, influencing factors, and applications in dentistry.

Methods

PubMed (National Library of Medicine) and Google Scholar databases were searched. Additionally, the scanner manufacturers' websites were accessed to obtain relevant data. Four authors independently selected the articles, books, and websites. To exclude duplicates and scrutinize the data, they were uploaded to Mendeley Data. In total, 135 articles, two books, and 17 websites were included.

Results

Research and clinical practice have shown that oral and facial scanners and CBCT can be used widely in various areas of dentistry with high accuracy.

Conclusion

Although further advancement of these devices is desirable, there is no doubt that digital technology represents the future of dentistry. Furthermore, the combined use of different devices may bring dentistry into a new era. These four devices will play a significant role in clinical utility with high accuracy. The combined use of these devices should be explored further.

Clinical significance

The four devices will play a significant role in clinical use with high accuracy. The combined use of these devices should be explored further.

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Periodontal ligament fibroblasts-derived exosomes induced by PGE2 inhibit human periodontal ligament stem cells osteogenic differentiation via activating miR-34c-5p/SATB2/ERK

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Publication date: Available online 15 August 2022

Source: Experimental Cell Research

Author(s): Chen Lin, Yingying Yang, Yingxue Wang, Heng Jing, Xinyi Bai, Zheng Hong, Chunxiang Zhang, Hui Gao, Linkun Zhang

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Translational Significance of CDKN2A/B Homozygous Deletion in IDH-Mutant Astrocytoma

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Abstract
Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy. However, recent molecular profiling has identified specific aggressive tumor subgroups with clear clinical prognostic implications that are independent of histologic grading. The homozygous deletion of CDKN2A/B is the strongest implicated independent indicator of poor prognosis within IDH-mutant astrocytoma, and the identification of this alteration in these lower histologic grade tumors transforms their biology toward an aggressive grade 4 phenotype clinically. CDKN2A/B homozygous deletion is now sufficient to define a grade 4 tumor in IDH-mutant astrocytomas regardless of histologic appearance, yet there are currently no effective molecularly informed targeted therapies for these tumors. The biologic impact of CDKN2A/B homozygous deletion in IDH-mutant tumors and the optimal treatmen t strategy for this molecular subgroup remains insufficiently explored. Here we review the current understanding of the translational significance of homozygous deletion of CDKN2A/B gene expression in IDH-mutant astrocytoma and associated diagnostic and therapeutic implications.
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