Κυριακή 18 Δεκεμβρίου 2022

Impact of SARS-CoV-2 variants on inpatient clinical outcome

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Abstract
Background
Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes.
Methods
Inpatients with COVID-19 at five hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features.
Results
Severe disease or death within 28 days occurred for 977 (29%) of 3,369 unvaccinated patients and 269 (22%) of 1,230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvac cinated patients, the relative risk of severe disease or death for Delta variant compared to ancestral lineages was 1.30 (95% confidence interval [CI] 1.11-1.49). Compared to Delta, this risk for Omicron patients was 0.72 (95% CI 0.59-0.88) and compared to ancestral lineages was 0.94 (95% CI 0.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio 0.40, 95% CI 0.30-0.54), but no significant outcome difference by variant.
Conclusions
Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.
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In silico study of SARS‐CoV‐2 Spike protein RBD and human ACE‐2 affinity dynamics across variants and Omicron sub‐variants

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Abstract

The coronavirus disease 2019 (COVID-19) virus outbreak continues worldwide, with many variants emerging, some of which are considered variants of concern (VOCs). The WHO designated Omicron as a VOC and assigned it under variant B.1.1.529. We used computational studies to examine the VOCs Omicron sub-variants (OSVs) and one variant of interest (VOI) in this study. Here we found that the binding affinity of human receptor angiotensin-converting enzyme 2 (hACE2) and RBDs increased in the order of wild type (Wuhan-strain) < Beta< Alpha< OmicronBA.5< Gamma< Delta< Omicron BA.2.75 < BA.1< BA.3< BA.2. Interactions between docked complexes revealed that the RBD residue positions like 452, 478, 493, 498, 501, and 505 are crucial in creating strong interactions with hACE2.Omicron BA.2 shows the highest binding capacity to the hACE2 receptor among all the mutant complexes. The BA.5's L452R, F486V and T478K mutation significantly impact the interaction network in th e BA.5 RBD-hACE2 interface. Here for the first time, we report the His505, an active residue on the RBD forming a salt bridge in the BA.2, leading to increased mutation stability. When the active RBD residues are mutated, binding affinity and intermolecular interactions increase across all mutant complexes. By examining the differences in different variants, this study may provide a solid foundation for structure-based drug design for newly emerging variants.

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Possible transmission of COVID‐19 epidemic by a dog as a passive mechanical carrier of SARS‐CoV‐2, Chongqing, China, 2022

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Abstract

An outbreak of COVID-19 was reported in Yongchuan district of Chongqing, China in March 2022, while the source was unknown. We aimed to investigate the origin and transmission route of the virus in the outbreak. We conducted field investigations for all cases and collected their epidemiological and clinical data. We performed gene sequencing and phylogenetic analysis for the cases, and draw the epidemic curve and the case relationship chart to analyze interactions and possible transmission mode of the outbreak. A total of 11 cases of COVID-19, including 5 patients and 6 asymptomatic cases were laboratory-confirmed in the outbreak. The branch of the virus was Omicron BA.2 which was introduced into Yongchuan district by a traveler in early March. Patient F and asymptomatic case G had never contact with other positive infected individuals, but close contact with their pet dog that sniffed the discarded cigarette butts and stepped on the sputum of patient B. Laboratory test results sh owed that the dog hair and kennel were positive for SARS-CoV-2, and the ten isolates were highly homologous to an epidemic strain in a province of China. The investigation suggested that the contaminated dog by SARS-CoV-2 can act as a passive mechanical carrier of the virus and might transmit the virus to humans through close contact. Our findings suggest that during the COVID-19 pandemic, increasing hygiene measures and hand washing after close contact with pets is essential to minimize the risk of community spread of the virus.

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Imaging of pediatric brain tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper

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Abstract

Tumors of the central nervous system are the most common solid malignancies in children and the most common cause of pediatric cancer-related mortality. Imaging plays a central role in diagnosis, staging, treatment planning, and response assessment of pediatric brain tumors. However, the substantial variability in brain tumor imaging protocols across institutions leads to variability in patient risk stratification and treatment decisions, and complicates comparisons of clinical trial results. This White Paper provides consensus-based imaging recommendations for evaluating pediatric patients with primary brain tumors. The proposed brain magnetic resonance imaging protocol recommendations balance advancements in imaging techniques with the practicality of deployment across most imaging centers.

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Key mutations in the spike protein of SARS‐CoV‐2 affecting neutralization resistance and viral internalization

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Abstract

To control the ongoing COVID-19 pandemic, a variety of SARS-CoV-2 vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I+S477N, V382L, K444R, L455F+S477N, L452M+F486L, F486L, Y508H, P521R, A626S, S477N+S698L, A701V, S477N+T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human ACE2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

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Comparison of 4‐ or 6‐implant supported immediate full‐arch fixed prostheses: A retrospective cohort study of 217 patients followed up for 3–13 years

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Abstract

Purpose

Choosing four or six implants to support immediate full-arch fixed prostheses (FAFPs) is still controversial worldwide. This study aims to analyze and compare the long-term results of All-on-4 and All-on-6.

Materials and Methods

This retrospective cohort study enrolled 217 patients rehabilitated with 1222 implants supporting 271 FAFPs, including 202 prostheses supported by 4 implants (All-on-4 group) and 69 prostheses supported by 6 implants (All-on-6 group), and followed up for 3–13 years. Implant survival, prosthesis survival, complications, and implant marginal bone loss (MBL) were evaluated and compared between two groups. Patient characteristics including age, gender, jaw, opposite dentition condition, smoking habit, bruxism, bone quantity and quality, cantilever length (CL), prosthesis material, and oral hygiene were analyzed to assess their influence on the clinical results of the two groups. Six surgeons and three prosthodontists who performed FAFPs more than 5 years were invited for questionnaires, to assess patient- and clinician-related influences on implant number.

Result

In general, All-on-4 group indicated no significant difference with All-on-6 group in the implant survival (implant-level: hazard ratio [HR] = 1.0 [95% confidence interval (CI): 0.8–1.2], P = 0.96; prosthesis-level: HR = 0.8 [95% CI: 0.3–1.8], P = 0.54), prosthesis survival (odds ratio [OR] = 0.8 [95% CI: 0.3–2.8], P = 0.56), biological complications (OR = 0.9 [95% CI: 0.5–1.8], P = 0.78), technical complications of provisional prosthesis (OR = 1.3 [95% CI: 0.7–2.3], P = 0.42), technical complications of definitive prosthesis (OR = 1.1 [95% CI: 0.6–2.2], P = 0.33) and the 1st, 5th, and 10th year MBL (P = 0.65, P = 0.28, P = 0.14). However, for specific covariates, including elderly patients, opposing natural/fixed dentition, smoking, bruxism, long CL, low bone density, and all acrylic provisional prostheses, All-on-6 was more predictable in some clinical measurements than All-on-4. The implant prosthodontists and the medium-experienced clinicians showed significant preference for All-on-6 (P < 0.05).

Conclusion

Based on this study, the long-term clinical results showed no significant difference between All-on-4 and All-on-6 groups in general. However, for some specific characteristics, All-on-6 seemed to be more predictable in some clinical measurements than All-on-4. For the clinicians' decision-making, medium-experienced clinicians and the implant prosthodontists showed significant preference for All-on-6.

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Synthetic CT in Musculoskeletal Disorders: A Systematic Review

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imageRepeated computed tomography (CT) examinations increase patients' ionizing radiation exposure and health costs, making an alternative method desirable. Cortical and trabecular bone, however, have short T2 relaxation times, causing low signal intensity on conventional magnetic resonance (MR) sequences. Different techniques are available to create a "CT-like" contrast of bone, such as ultrashort echo time, zero echo time, gradient-echo, and susceptibility-weighted image MR sequences, and artificial intelligence. This systematic review summarizes the essential technical background and developmen ts of ultrashort echo time, zero echo time, gradient-echo, susceptibility-weighted image MR imaging sequences and artificial intelligence; presents studies on research and clinical applications of "CT-like" MR imaging; and describes their main advantages and limitations. We also discuss future opportunities in research, which patients would benefit the most, the most appropriate situations for using the technique, and the potential to replace CT in the clinical workflow.
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Synthetic Contrasts in Musculoskeletal MRI: A Review

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imageThis review summarizes the existing techniques and methods used to generate synthetic contrasts from magnetic resonance imaging data focusing on musculoskeletal magnetic resonance imaging. To that end, the different approaches were categorized into 3 different methodological groups: mathematical image transformation, physics-based, and data-driven approaches. Each group is characterized, followed by examples and a brief overview of their clinical validation, if present. Finally, we will discuss the advantages, disadvantages, and caveats of synthetic contrasts, focusing on the preservation of im age information, validation, and aspects of the clinical workflow.
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Quantitative MRI for Evaluation of Musculoskeletal Disease: Cartilage and Muscle Composition, Joint Inflammation, and Biomechanics in Osteoarthritis

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imageMagnetic resonance imaging (MRI) is a valuable tool for evaluating musculoskeletal disease as it offers a range of image contrasts that are sensitive to underlying tissue biochemical composition and microstructure. Although MRI has the ability to provide high-resolution, information-rich images suitable for musculoskeletal applications, most MRI utilization remains in qualitative evaluation. Quantitative MRI (qMRI) provides additional value beyond qualitative assessment via objective metrics that can support disease characterization, disease progression monitoring, or therapy response. In t his review, musculoskeletal qMRI techniques are summarized with a focus on techniques developed for osteoarthritis evaluation. Cartilage compositional MRI methods are described with a detailed discussion on relaxometric mapping (T2, T2*, T1ρ) without contrast agents. Methods to assess inflammation are described, including perfusion imaging, volume and signal changes, contrast-enhanced T1 mapping, and semiquantitative scoring systems. Quantitative characterization of structure and function by bone shape modeling and joint kinematics are described. Muscle evaluation by qMRI is discussed, including size (area, volume), relaxometric mapping (T1, T2, T1ρ), fat fraction quantification, diffusion imaging, and metabolic assessment by 31P-MR and creatine chemical exchange saturation transfer. Other notable technologies to support qMRI in musculoskeletal evaluation are described, including magnetic resonance fingerprinting, ultrashort echo time imaging, ultrahigh-field MRI, and hybrid MRI-p ositron emission tomography. Challenges for adopting and using qMRI in musculoskeletal evaluation are discussed, including the need for metal artifact suppression and qMRI standardization.
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Brachial Plexus Magnetic Resonance Neurography: Technical Challenges and Solutions

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imageMagnetic resonance neurography of the brachial plexus (BP) is challenging owing to its complex anatomy and technical obstacles around this anatomic region. Magnetic resonance techniques to improve image quality center around increasing nerve-to-background contrast ratio and mitigating imaging artifacts. General considerations include unilateral imaging of the BP at 3.0 T, appropriate selection and placement of surface coils, and optimization of pulse sequences. Technical considerations to improve nerve conspicuity include fat, vascular, and respiratory artifact suppression techniques; metal ar tifact reduction techniques; and 3-dimensional sequences. Specific optimization of these techniques for BP magnetic resonance neurography greatly improves image quality and diagnostic confidence to help guide nonoperative and operative management.
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