Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

alexandrossfakianakis shared this article with you from Inoreader Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades via Journal of Medical Virology Abstract COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly. This article is protected by copyright. All rights reserved. View on Web

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Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

alexandrossfakianakis shared this article with you from Inoreader Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol via Pediatric Blood & Cancer Abstract The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies. View on Web

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Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices

alexandrossfakianakis shared this article with you from Inoreader Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices via American Journal of Epidemiology - Advance Access Abstract Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation patterns (DNAm)), we report on three different approaches – 1 incorrect and 2 correct – in the epidemiologic literature on treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used the correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%), or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introdu ced by the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias to the null, and we discuss implications for extant research and recommendations for best practices. View on Web

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Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups

alexandrossfakianakis shared this article with you from Inoreader Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups via Neuro-Oncology Advance Access Abstract Background The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse. Methods Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated. Results Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering de lineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations. Conclusion These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of r elapse. View on Web

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Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study via Clinical Infectious Diseases Advance Access ABSTRACT Background Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron). Methods This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status. Results The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status. Conclusions Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms. View on Web

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Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme

alexandrossfakianakis shared this article with you from Inoreader Interesting Findings in 68Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme via Clinical Nuclear Medicine - Published Ahead-of-Print A 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fi broblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas. View on Web

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Molecular evolution of the human monkeypox virus

alexandrossfakianakis shared this article with you from Inoreader Molecular evolution of the human monkeypox virus via Journal of Medical Virology ABSTRACT Background Recently, in 2022, new cases of human monkeypox virus (hMPXV) occurred in Europe and North America. The first case was reported in Europe in May 2022, and subsequently, more than 50,000 new cases were confirmed in 100 countries. Currently, the classification of hMPXV according to the nextstrain occurs in five big clades (1A, A.1, A.2, A.1.1, and B.1). Aims According to the resurgence of smallpox-like disease caused by hMPXV and the spread of the virus to the European and American continents, in the present study, we review and summarize the molecular evolution of the hMPXV, determining the molecular evolution of the main clades. Methods A total of 442 hMPXV whole-genome sequences (WGS) with available information from the country and sampling date (between October 2017 and 2022), were obtained and evaluated using the Bayesian method. Results The clade B.1 which is currently circulating was the most frequent (n=415; 93.9%). The other clades presented the following frequencies: 1A (n=13; 2.9%), A.1 (n=10; 2.3%), A.2 (n=3; 0.7%) and A.1.1 (n=1; 0.2%) The overall nucleotide divergence of hMPXV was 5,590e-5. The 1A clade was detected between 2017 and 2020. A.1 was observed, and between 2019 and 2022 some A.2 sequences were detected. In 2022, the great predominance of B.1 was observed. The common ancestor of the hMPXV belongs to the clade 1A and the time to the Most Recent Common Ancestor (tMRCA) was 2017-04-04 (Highest Posterior Density 95% (HPD95%): 2017-03-09; 2017-08-04) on the West African continent. The tMRCA of A.1 was 2018-05-21 (HPD95%: 2018-05-20; 2018-07-04) with divergence of 6.885e-5 substitutions per site per year (ssy). This clade was of West African origin but was eventually detected in European countries. Also, A.2 was detected with sequences of North America and showed tMRCA of 2019-07-15 (HPD95%: 2018-11- 18; 2020-02-24). A.1.1 showed tMRCA from 2021-06-05 (HPD95%: 2021-06-05; 2021-11-26) and this clade was detected in North America and was the precursor for the globally spreading B.1 which tMRCA was 2022-04-26 (HPD95%: 2022-02-27; 2022-04-26). hMPXV has been spread from West Africa to the United Kingdom, Israel, Singapore, the USA, Canada, Portugal, Spain, Ireland, France, Belgium, the Netherlands, Switzerland, Germany, Italy, Slovenia, Austria, the Republic Czech, Sweden, and Finland. hMPXV also reached countries such as Brazil, Mexico, Australia, and Taiwan. Conclusion The common ancestor of the hMPXV belongs to the clade 1A with origin in the West African continent. Clade B.1 was responsible for the recent widespread worldwide. Immunization to prevent the spread of hMPXV is not yet available to the public, future studies should focus on the development of effective vaccines to contain the spread of this virus. This article is protected by copyright. All rights reserved. View on Web

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Prevention of peri‐implant disease in edentulous patients with fixed implant rehabilitations

alexandrossfakianakis shared this article with you from Inoreader Prevention of peri‐implant disease in edentulous patients with fixed implant rehabilitations via Clinical Implant Dentistry and Related Research Abstract Objectives To provide an overview about the current approaches to prevent peri-implant diseases in edentulous patients with complete-arch implant-supported prostheses, and to review the clinical applications of the latest digital technologies for implant prosthodontics. Methods A review of the guidelines to prevent peri-implant diseases in patient's receiving complete-arch implant-supported prostheses including facially driven treatment planning procedures using either conventional or digital methods, computer-aided implant planning procedures, and prosthodontic design variables including the optimal number and distribution of dental implants, implant to abutment connection type, implant or abutment level design, screw- or cement-retained alternatives, prostheses contours, and material selection is provided. Furthermore, an outline of the current therapeutic management approaches to address peri-implant diseases is reviewed. Conclusions Clinicians should understand and know different planning and design-related variables that can affect biological and mechanical complication rates of complete-arch implant-supported prostheses. Maintenance protocols are fundamental for minimizing biological and mechanical complications. View on Web

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Pathogen‐agnostic immune biomarkers that predict infection after solid organ transplantation

alexandrossfakianakis shared this article with you from Inoreader Pathogen‐agnostic immune biomarkers that predict infection after solid organ transplantation via Transplant Infectious Disease Abstract Solid organ transplant recipients (SOTRs) remain at high risk for infection throughout their post-transplant course. Dosing of immunosuppressive medications, strategies that prevent infection, and choice of empiric antimicrobial treatment could be optimized by a better understanding of an individual patient's risk for infectious complications. Diagnostic tests that qualitatively or quantitatively measure the function of the immune system and/or its response to infection may be useful for individualized management decisions. Numerous studies have identified an association between infectious outcomes after solid organ transplantation (SOT) and the results of a variety of non-pathogen-specific or "pathogen-agnostic" immune monitoring tests. These biomarkers include humoral immune markers, functional or quantitative assessments of cellular immunity, transcriptomic-based diagnostics, and replication of viruses within the human virome, which have been used to predict or diagnose a v ariety of different infectious diseases complicating SOT. In this narrative review, we discuss several host-derived immune biomarkers that show promise for either predicting or diagnosing infection among SOTRs. However, additional studies are needed to determine the optimal use of immune response testing. Whether immune biomarkers contribute added benefits to current standard clinical care has not yet been determined. Testing must be validated across a range of clinical scenarios, including surveillance to predict infection risk and diagnosis of active infection at various time points post transplant. View on Web

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Perio‐prosthodontic pontic site management, part I: Pontic designs and their current applications

alexandrossfakianakis shared this article with you from Inoreader Perio‐prosthodontic pontic site management, part I: Pontic designs and their current applications via Journal of Esthetic and Restorative Dentistry Abstract Objective Emulating natural dentition with dental implant restorations is challenging, increasing its complexity when a pontic area must be restored. Many different methods have been described to solve this problem. The pontic designs which have been proposed have specific indications and may require additional treatments, including soft tissue augmentation procedures, to increase the possibility of an esthetically pleasing and biologically tolerable outcome. Proper conditioning of the soft tissues during the interim restoration stage and adequate communication with the laboratory are also critical factors to a successful outcome. This article describes the different approaches to restoring pontic sites with different degrees of complexity, their clinical indications, and limitations viewed from a perio-prosthodontic approach. Clinical Considerations Different clinical scenarios for pontic sites require different approaches. Missing hard and soft tissues can be replaced by surgical or prosthetic means. Understanding the clinical indications and implications of the different pontic designs allows the clinician to make good decisions when planning and treating patients that require replacement of pontic spaces leading to more successful outcomes. Conclusions Different pontic designs have specific indications as well as biologic and esthetic prognoses. Selection of a good design, proper modifications during the provisionalization stage, and adequate communication with the dental laboratory will lead to higher chances of esthetic and biological success. Clinical Significance The proper pontic design allows for esthetically pleasing pontic sites which emulate natural emergence from the soft tissues while promoting biological stability. View on Web

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