Evolution and Emergence of Primate Specific Interferon Regulatory Factor 9

alexandrossfakianakis shared this article with you from Inoreader Evolution and Emergence of Primate Specific Interferon Regulatory Factor 9 via Journal of Medical Virology Abstract The binding of interferon (IFN) to its receptors leads to formation of IFN-stimulated gene factor 3 (ISGF3) complex that activates the transcription of cellular IFN regulated genes. IFN regulatory factor 9 (IRF9, also called ISGF3γ or p48) is a key component of ISGF3. However, there is limited knowledge regarding the molecular evolution of IRF9 among vertebrates. In this study, we have identified the existence of the IRF9 gene in cartilaginous fish (sharks). Among primates, several isoforms unique to old world moneys and great apes are identified. These IRF9 isoforms are named as primate specific IRF9 (PS-IRF9) to distinguish from canonical IRF9. PS-IRF9 originates from a unique exon usage and differential splicing in IRF9 gene. While the N-terminus are identical for all IRF9s, the C-terminal regions of the PS-IRF9 are completely different from canonical IRF9. In humans, two PS-IRF9s are identified and their RNA transcripts were detected in human primary pe ripheral blood mononuclear cells. In addition, human PS-IRF9 proteins were detected in human cell lines. Sharing the N-terminal exons with the canonical IRF9 proteins, PS-IRF9 is predicted to bind to the same DNA sequences as the canonical IRF9 proteins. Because the C-terminal regions of IRFs are the determinants of IRF functions, PS-IRF9 may offer unique biological functions and represent a novel signaling molecule involved in the regulation of the IFN pathway in a primate specific manner. This article is protected by copyright. All rights reserved. View on Web

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Surveillance, Isolation and Genomic Characterization of Pteropine orthoreovirus of Probable Bat Origin Among Patients with Acute Respiratory Infection in Malaysia

alexandrossfakianakis shared this article with you from Inoreader Surveillance, Isolation and Genomic Characterization of Pteropine orthoreovirus of Probable Bat Origin Among Patients with Acute Respiratory Infection in Malaysia via Journal of Medical Virology Abstract Pteropine orthoreovirus (PRV), an emerging bat-borne virus, has been linked to cases of acute respiratory infections (ARI) in humans. The prevalence, epidemiology and genomic diversity of PRV among ARI of unknown origin were studied. Among 632 urban outpatients tested negative for all known respiratory viruses, 2.2% were PRV-positive. Patients mainly presented with moderate to severe forms of cough, sore throat and muscle ache, but rarely with fever. Phylogenetic analysis revealed that over 90% of patients infected with the Melaka virus (MelV)-like PRV, while one patient infected with the Pulau virus previously found only in fruit bats. Human oral keratinocytes and nasopharyngeal epithelial cells were susceptible to clinical isolates of PRV, including the newly isolated MelV-like 12MYKLU1034. Whole genome sequence of 12MYKLU1034 using Nanopore technique revealed a novel reassortant strain. Evolutionary analysis of the global PRV strains suggests the continuous evolution of PRV through genetic reassortment among PRV strains circulating in human, bats and non-human primate hosts, creating a spectrum of reassortant lineages with complex evolutionary characteristics. In summary, the role of PRV as a common etiologic agent of ARI is evident. Continuous monitoring of PRV prevalence, pathogenicity and diversity among human and animal hosts is important to trace the emergence of novel reassortants. This article is protected by copyright. All rights reserved. View on Web

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Enhanced recombination among omicron subvariants of SARS‐CoV‐2 contributes to viral immune escape

alexandrossfakianakis shared this article with you from Inoreader Enhanced recombination among omicron subvariants of SARS‐CoV‐2 contributes to viral immune escape via Journal of Medical Virology Abstract Genetic recombination is an important driver of SARS-CoV-2 evolution, which requires the co-infection of a single host cell with different SARS-CoV-2 strains. To understand the emergence and prevalence of recombinant SARS-CoV-2 lineages through time and space, we analyzed SARS-CoV-2 genome sequences collected from November 2019 to July 2022. We observed an extraordinary increase in the emergence of SARS-CoV-2 recombinant lineages during the Omicron wave, particularly in Northern America and Europe. This phenomenon was independent of the sequencing frequency or genetic diversity of circulating SARS-CoV-2 strains. The recombination breakpoints were more prevalent in the 3' UTR of the viral genome. Importantly, we noted the enrichment of certain amino acids in the spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies and increase ACE2 receptor binding in some cases. We also observed I42V amino acid change genetically fi xated in the NSP14 of the Omicron lineage, which needs further characterization for its potential role in enhanced recombination. Overall, we report the important and timely observation of accelerated recombination in the currently circulating SARS-CoV-2 Omicron variants and explore their potential contribution to viral fitness, particularly immune escape. This article is protected by copyright. All rights reserved. View on Web

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Use of gemcitabine, oxaliplatin, and anti‐CD20 therapy in children and adolescents with non‐Hodgkin lymphoma unfit for intensive therapy

alexandrossfakianakis shared this article with you from Inoreader Use of gemcitabine, oxaliplatin, and anti‐CD20 therapy in children and adolescents with non‐Hodgkin lymphoma unfit for intensive therapy via Pediatric Blood & Cancer Abstract Multiagent immunochemotherapy affords excellent outcomes in pediatric non-Hodgkin lymphoma (NHL); however, scarce data exist for patients unfit for intensive treatment. Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is well tolerated and efficacious in elderly adults with NHL; however, its use has not been described in pediatrics. In this retrospective, single-center study, six children with mature B-cell NHL and significant comorbidities received anti-CD20 therapy with GemOx (rituximab or obinutuzumab or ofatumumab with gemcitabine and oxaliplatin [R/O-GemOx]). R/O-GemOx was well tolerated and resulted in complete response in two of three patients with newly diagnosed NHL and one of three patients with primary refractory NHL. R/O-GemOx is a viable treatment option for children with NHL who cannot tolerate intensive therapy. View on Web

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Serial In‐Office Steroid Injections for Airway Stenosis: Long‐Term Benefit and Cost Analysis

alexandrossfakianakis shared this article with you from Inoreader Serial In‐Office Steroid Injections for Airway Stenosis: Long‐Term Benefit and Cost Analysis via The Laryngoscope Serial in office steroid injection help avoid operative intervention regardless of stenosis etiology. Follow up of at least 2 years suggest that serial in office steroid injection can avoid operative intervention long term. There is potential cost savings associated with serial steroid injection over traditional endoscopic dilation. Objectives To evaluate the long-term benefit of serial in-office steroid injections (SISI) in the treatment of subglottic and proximal tracheal stenosis (SG/PTS). Evaluate cost of SISI compared to endoscopic dilation (ED). Study Design Retrospective study and cost analysis. Methods All patients with SGS/PTS with at least two consecutive in-office steroid injections between 2013 and 2021 were evaluated. Patients with less than 2 years of follow-up data after the initial SISI series were excluded. Demographics, etiology of stenosis, total injections performed, time between steroid series, surgery-free interval (SFI) and adverse events were collected. For patients with known surgical history before SISI, pre-SISI SFI was compared. Institutional billing records and the national CMS average reimbursement were evaluated. Total charges for three treatment strategies (ED alone, ED with post-operative SISI and primary intervention with SISI) were also compared. Results Forty-nine patients were included; 29 (59%) idiopathic, 11 (22%) traumatic and 9 (18%) rheumatologic. Mean (SD) follow-up time after the first SISI was 3.41 years (1.5), range (2.08–7.25 years). 79% (39/49) did not require additional surgery during the entire follow-up period. The SFI improved from a mean 13.5 months (SD 12.6; range 2–42 months) pre-SISI to a mean (SD) of 42 months (SD 20.2; range 10–87 months) (p < 0.0001) after SISI. Annual average charges for ED alone in our cohort was $15,383.28, compared to $7,070.04 for SISI. Conclusions SISI are an effective treatment for patients with SG/PTS. In-office steroid injections could offer cost savings for the patient. Level of Evidence 4 Laryngoscope, 2023 View on Web

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Compression of the Vertebral Artery by the Thyroid Cartilage Causing Vertebrobasilar Insufficiency

alexandrossfakianakis shared this article with you from Inoreader Compression of the Vertebral Artery by the Thyroid Cartilage Causing Vertebrobasilar Insufficiency via The Laryngoscope Mechanical compression of the vertebral artery during mouth opening by the thyroid cartilage. Successfully resolved by resection of the thyroid cartilage. Background This retrospective case report describes a rare presentation of VBI in a young male patient. Aims Share a rare cause of VBI in a young patient. Materials & Methods The patient presented with recurrent episodes of dizziness and a history of several cerebellar infarcts. Imaging revealed the right vertebral artery was being mechanically compressed by the right superior cornu of the thyroid cartilage during mouth opening. Surgical resection of the right superior cornu of the thyroid cartilage was performed. Results Intraoperative angiography revealed a right vertebral artery without compression during mouth opening. Discussion Clinicians should consider the thyroid cartilage as a potential source of recurrent VBI due to mechanical compression of the VA. Conclusion Resection of the causative portion of the thyroid cartilage resolved the compression in this case, and should be employed in similar cases. Laryngoscope, 2023 View on Web

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Relationship of Lesion Location to Postoperative Steroid Use in Eosinophilic Chronic Rhinosinusitis

alexandrossfakianakis shared this article with you from Inoreader Relationship of Lesion Location to Postoperative Steroid Use in Eosinophilic Chronic Rhinosinusitis via The Laryngoscope The relationship between steroid use and endoscopic lesion location in the postoperative course of ECRS patients was examined, and sphenoethmoidal recess lesions were a risk factor for the need for postoperative steroids. These findings call for more appropriate use of steroids in the postoperative management of ECRS. Objectives Eosinophilic chronic rhinosinusitis (ECRS) is known to recur after surgery. The treatment choice for recurrent ECRS, such as oral steroids or biological agents, must be chosen carefully, and identifying the lesion location may be useful. This study aimed to evaluate the postoperative course of ECRS patients and assess the relationship between endoscopic lesion location and postoperative oral steroid use. Methods Patients with chronic rhinosinusitis who underwent bilateral endoscopic sinus surgery from April 2018 to March 2020 were divided into two groups based on the presence or absence of oral steroid use after surgery. The primary endpoint was the lesion location on endoscopic findings during surgery: middle turbinate, middle meatus, superior turbinate, superior meatus, nasal septum, and sphenoethmoidal recess. Subjective symptoms, blood tests, and computerized tomography (CT) findings (Lund-Mackay score) were evaluated as secondary endpoints. Results Among 264 patients, 88 were diagnosed histologically with ECRS (mean 48.98 ± 1.40 years, 67 males/21 females). Twenty-three patients were steroid-using, 65 were steroid-free, and six stopped attending their appointments. Patients with sphenoethmoidal recess lesions were significantly more likely to require steroids (p = 0.019). There was a significant association between steroid use and younger age (p = 0.041), olfactory dysfunction (p = 0.021), and all sinuses (Frontal sinus: p < 0.001, Anterior ethmoid sinus: p = 0.002, Posterior ethmoid sinus: p = 0.011, Maxillary sinus: p = 0.018, Sphenoid sinus: p = 0.034, Total score: p < 0.001). Conclusion A sphenoethmoidal recess lesion was a risk factor for requiring postoperative steroids. Young age, olfactory dysfunction, and preoperative severe CT findings were also significant risk factors. Level of Evidence 3 Laryngoscope, 2023 View on Web

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Radiological evolution of progestogen‐induced meningioma: A monocentric retrospective study

alexandrossfakianakis shared this article with you from Inoreader Radiological evolution of progestogen‐induced meningioma: A monocentric retrospective study via Fundamental & Clinical Pharmacology Abstract Context Cyproterone acetate (CPA) is known to induce meningioma, and recently, nomegestrol acetate (NMA) and chlormadinone acetate (CMA) were also involved. Progestagen-induced meningioma management starts with progestogen discontinuation and is either interventional (surgery and/or radiotherapy) or conservative (clinical and MRI radiological follow-up). We performed a retrospective volumetric radiological outcome study of progestogen-induced meningiomas diagnosed in our hospital. Method We analysed progestogen-related meningiomas diagnosed until 30 June 2021, with at least one diagnostic and one follow-up MRI results. Meningioma volumes were centrally retrospectively measured using a T1-weighted 3D millimeter sequence with gadolinium injection on a post-processing console. Results We analysed 98 meningiomas of 38 females and one transgender (male-to-female), of which 25 (64.1%) had taken CPA, 7 (17.9%) NMA, 3 (7.7%) CMA, and 4 (10.2%) several progestogens. Eleven patients (24 meningiomas) underwent interventional management, 7 patients had meningiomas followed by conservative or interventional management, and 21 patients (51 meningiomas) had only conservative management. Of these 21 patients, 17 had discontinued their progestogen less than 6 months before, of which 14 (82.3%) had decreased or stable meningioma(s) during a 24-month median follow-up [3 to 75] period. Overall four of the 39 patients experienced meningioma progression (three during conservative treatment and one after surgery), including two patients who had continued NMA or CMA treatment several years after diagnosis. Conclusion Our study confirms a generally favorable outcome of progestogen-related meningioma after conservative treatment, especially for CPA. It also underlines the need for progestogen discontinuation at meningioma diagnosis. View on Web

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Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias

alexandrossfakianakis shared this article with you from Inoreader Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias via American Journal of Epidemiology - Advance Access Abstract Concerns about the duration of protection conferred by COVID-19 vaccines have arisen in postlicensure evaluations. "Depletion of susceptibles" bias driven by differential accrual of infection among vaccinated and unvaccinated individuals may obscure vaccine effectiveness (VE) estimates, hindering interpretation. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design case-control study to estimate VE of mRNA-based CO VID-19 vaccines between 23 February and 5 December 2021. We analyzed waning protection following two vaccine doses using conditional logistic regression models. Additionally, we used data from a population-based serological study to adjust for "depletion-of-susceptibles" bias and estimated VE for 3 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval: 83.8-95.4%) at 14 days after second-dose receipt and declined to 50.8% (31.2-75.6%) at 7 months. Adjusting for depletion-of-susceptibles, we estimated VE of 53.2% (23.6-71.2%) at 7 months after primary mRNA vaccination series. A booster dose of BN162b2 or mRNA-1273 increased VE to 95.0% (82.8-98.6%). These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19. View on Web

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The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing

alexandrossfakianakis shared this article with you from Inoreader The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing via Clinical Infectious Diseases Advance Access Abstract Background Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literat ure. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. Objective The IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. Methods A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommenda tions Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. Conclusions U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved s elf-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate. View on Web

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