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Κυριακή 21 Αυγούστου 2022

Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19

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Abstract
Background
Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear.
Methods
We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed C ovid-19 between December 1, 2021, and April 18, 2022, were included. Cohorts were developed based on the use of NMV-r within five days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-days follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, Covid-19 associated complications, and diagnostic test utilization.
Results
After propensity score matching, 1,130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort as compared to 163 (14.4%) patients in the non-NMV-r cohort (OR 0.5, CI 0.39-0.67; p<0.005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing were noted in NM V-r treated patients. There was no apparent increase serious complications between days 10 to 30.
Conclusion
Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.
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Long‐term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

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Long-term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

Premature infants undergoing patent ductus arteriosus ligation are at risk for vocal fold paralysis leading to long term voice and swallowing complications. In this study, we review risk factors for vocal fold paralysis and offer insight into long term outcomes and further treatment needs in this unique patient population.


Introduction

In patients undergoing patent ductus arteriosus (PDA) ligation there is a significant risk of left vocal fold paralysis (LVFP) particularly in premature neonates who are small for gestational age. The objective of this study is to determine the incidence of LVFP in infants following PDA ligation and report on long-term outcomes in patients with LVFP.

Methods

We performed a prospective study of patients undergoing PDA ligation in the newborn intensive care unit (NICU) between April 2004 and May 2014. Following PDA ligation, flexible laryngoscopy was performed to assess vocal fold mobility. Patients were then followed longitudinally to determine long-term outcomes.

Results

A total of 163 infants underwent PDA ligation. Thirty-six patients (22%) developed LVFP following the procedure. Twenty-five percent of neonates <1500 g experienced LVFP versus 5% of patients >1500 g (p = 0.033). Patients with LVFP were more likely to require a feeding tube (64% vs. 19.6%; p < 0.05) and spent more time in the NICU (135 days vs. 106 days; p < 0.05). Twenty-four patients received long-term follow-up. Six (25%) had complete resolution of LVFP, 10 (42%) were compensated, and 8 (33%) demonstrated persistent LVFP with no improvement.

Conclusions

The incidence of LVFP after PDA ligation is high especially in extremely low birth weight children. The majority of patients recovered well with time, but further surgical intervention was required in uncompensated cases. Long-term follow-up of these patients is needed to ensure improvement. Laryngoscope, 2022

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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.

This article is protected by copyright. All rights reserved.

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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

Influence of geometric dimensions on early failures of adhesively retained composite resin core build‐ups

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Abstract

Objective

To determine the influence of the geometric dimensions of core build-ups on early core build-up failure, that is, loss before definitive prosthesis cementation.

Materials and Methods

Adhesive core build-ups of exclusively vital teeth in 114 participants were evaluated (n materials: 40 Rebilda DC, 38 Multicore Flow, 36 Clearfil DC Core; n teeth: 8 incisors, 54 premolars, 52 molars). Impressions of the abutment teeth were made (1) after removal of insufficient restorations/caries and (2) after core build-up and preparation for a fixed prosthesis. Digitized model surfaces of both situations were aligned (Geomagic Design X) and core build-up volume (V CBU), remaining hard tissue volume (V Abut), and size of the adhesive surface (A adh) were assessed. The derived measure d CBU = V CBU/A adh can be interpreted as mean arithmetic core build-up thickness. Associations between participant or core build-up design characteristics and the occurrence of early failures were statistically evaluated (SPSS v27, α = 0.05).

Results

A total of six (5.3%) core build-up failures were registered. Higher participant age, greater core build-up volume V CBU and greater arithmetic uniform thickness d CBU were associated with a greater incidence of failure in bivariate and univariate, however, not in multivariate statistics.

Conclusions

Core build-up volume and thickness were associated with early success or failure.

Clinical Significance

In the case of voluminous/thick core build-ups in relation to the adhesive surface, additional measures, such as the preparation of retentive elements to increase the bonding area, might be considered to reduce the risk of early core build-up failure.

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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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