Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis

alexandrossfakianakis shared this article with you from Inoreader Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis via Neuro-Oncology Advance Access Abstract Background Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li–Fraumeni syndrome, though only about a half of CPCs develop from syndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course. Methods This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted 5.2 years (absolute range 2.8–12.6 years ). Results All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, notably multiple monosomies, were highly typical. In seven tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0±17.9% vs. 85.7±13.2%; p=0.009. Transcriptomically, the cohort split into two polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3±17.8% vs. 100%; p=0.012. Conclusion CPCs split into at least two molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates with survival. The distinct ion may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Impact of SARS-CoV-2 variants on inpatient clinical outcome via Clinical Infectious Diseases Advance Access 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. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader Possible transmission of COVID‐19 epidemic by a dog as a passive mechanical carrier of SARS‐CoV‐2, Chongqing, China, 2022 via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Key mutations in the spike protein of SARS‐CoV‐2 affecting neutralization resistance and viral internalization via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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Polycaprolactone versus collagen membrane and 1‐year clinical outcomes: A randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Polycaprolactone versus collagen membrane and 1‐year clinical outcomes: A randomized controlled trial via Clinical Implant Dentistry and Related Research Abstract Background Polycaprolactone (PCL) is a synthetic aliphatic polyester widely used in biomedical applications with biodegradability in the body and promotes cell proliferation and differentiation. A newly developed bilayered PCL membrane was developed for possibly being used as a membrane in guided bone regeneration (GBR). Purpose To compare the clinical efficacy between a newly developed bilayered PCL membrane with a Cytoplast™ RTM collagen membrane for GBR with simultaneous implant placement. Materials and Methods Twenty-four patients were randomized to PCL or RTM group, and a total of 24 dental implants were placed. Primary outcomes were patient mean buccal bone thickness (BBT) immediately postimplantation and at 6 months using cone-beam CT and soft tissue surface dimensional changes (STC) at crown insertion, 6 months, and 1 year after loading using intraoral scanner. Secondary outcomes included success rate, clinical parameters, healing index, implant stability, pink esthetic score, and marginal bone levels. Results The percentage of reduced BBT at 6 months was 32.38%, 25.94%, and 23.96% in the test group and 34.42%, 14.75%, and 6.34% in the control group at the corresponding levels. The mean difference of changed BBT associated with PCL membrane, when compared to collagen membrane, at 6 months was −0.02 ± 0.18 mm (95% confidence interval [CI]: −0.40 to 0.35), 0.29 ± 0.28 mm (95% CI: −0.29 to 0.87), and 0.62 ± 0.38 mm (95% CI: −0.17 to 1.42) at 0, 2, and 4 mm from implant shoulder. Minimal loss of STC was observed in both groups up to 1 year of loading. The mean difference loss of surface dimensional change associated with PCL membrane, when compared to collagen membrane, at 1 year of loading was 0.31 ± 0.19 mm (95% CI: −0.07 to 0.70), 0.22 ± 0.26 mm (95% CI: −0.33 to 0.76), and 0.17 ± 0.30 mm (95% CI: −0.45 to 0.78) at 0, 2, and 4 mm from implant shoulder. None of these differences were statistically significant (unpaired t-test, degrees of freedom [df] = 22; p > 0.05). Conclusion Within the limits of this trial, both barrier membranes resulted in comparable outcomes for GBR with implant placement after 1 year in function. Further research is necessary with a larger sample size. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader 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 via Clinical Implant Dentistry and Related Research 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. View on Web

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Synthetic CT in Musculoskeletal Disorders: A Systematic Review

alexandrossfakianakis shared this article with you from Inoreader Synthetic CT in Musculoskeletal Disorders: A Systematic Review via Investigative Radiology - Current Issue Repeated 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. View on Web

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