KS05.5.A Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

alexandrossfakianakis shared this article with you from Inoreader KS05.5.A Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients via # Neuro-Oncology Current Issue Abstract Background In glioma patients, multimodal therapy and recurrent tumor result in local brain tissue changes, characterized by pathologic findings in structural MRI and metabolic PET images. Little is known about these different lesion types' impact on the local white matter fiber architecture and clinical outcome. Patients and Methods This study included data from 121 pretreated patients (median age, 52 years; ECOG, 01) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median time of 14 months (range, 1-214 months), post-therapeutic structural and metabolic findings were evaluated using anatomical MRI and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET acquired on a 3T hybrid PET/MR scanner. Local fiber densi ty was estimated from tractography based on highangular resolution diffusion-weighted imaging. A cohort of 121 healthy subjects selected from the 1000BRAINS study and matched for age, gender and education served as a control group. Results The median volume of resection cavities, contrast-enhancing regions, regions with pathologically increased FET uptake, and T2/FLAIR hyperintense regions amounted to 20.9, 7.9, 30.3, and 53.4 mL, respectively. Compared to the control group, the average local fiber density in these regions was significantly reduced (p<0.001). Resection cavities showed the highest reduction, followed by contrast-enhancing lesions and metabolically active tumors on FET PET (relative fiber density reduction, -87%, -65%, -55%, respectively). The local fiber density was inversely related (p=0.005) to the FET uptake in recurrent tumors. T2/FLAIR hyperintense lesions, either assigned to peritumoral edema in recurrent glioma or radiation-induced gliosis, had a c omparable impact on reducing fiber density (48% and 41%, respectively). The total fiber loss (average fiber loss multiplied by lesion volume) associated with contrast-enhancing lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on the general performance status of the patients (ECOG score). Conclusions Our results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance due to the larger volume affected. Funding Funded by the 1000BRAINS study (INM, Research Centre Juelich, Germany), Horizon 2020 (Grant No. 945539 (HBP SGA3; SC)), and Heinz Nixdorf Foundation. View on Web

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Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial via Clinical Infectious Diseases Advance Access Abstract Background Despite vaccination, many remain vulnerable to COVID-19 and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based upon perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. Evidence from large randomized controlled trials (RCT) is lacking. Methods In this multicenter double-blinded placebo-controlled RCT, adults with early mild-to-moderate COVID-19 were 1:1 randomized to favipiravir or placebo. The study evaluated time to sustained clinical recovery (TT-SCR), COVID-19 progression, and cessation of viral shedding. Results Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, 89.0% unvaccinated, 70.3% SARS-CoV-2 seronegative, and 77.8% had risk factors for COVID-19 progression. The median time from symptom presentation and from positive test to randomization was three and two days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; p = 0.80), COVID-19 progression [11 patients each (1.9% vs. 1.8%); p = 0.96], time to undetectable virus [median = 6 days, 95% CI (6-8) vs. 7 days, 95% CI (6-9)], or in undetectable virus by end of therapy (73.4% vs. 72.3%; p = 0.94). Outcomes were consistent across the analyzed sub-groups. Adverse events were observed in 13.8% and 14.8% of favipiravir-treated and placebo-treated subjects, respectively. Uric acid elevation was more frequent among favipiravir-treated subjects (19.9% vs. 2.8%). Conclusions Favipiravir was well tolerated but lacked efficacy in TT-SCR, progression to severe COVID-19, or cessation of viral shedding and should not be used to treat patients with COVID-19. View on Web

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Outcomes of Partial Oral Antibiotic Treatment for Complicated S. aureus Bacteremia in People Who Inject Drugs

alexandrossfakianakis shared this article with you from Inoreader Outcomes of Partial Oral Antibiotic Treatment for Complicated S. aureus Bacteremia in People Who Inject Drugs via Clinical Infectious Diseases Advance Access Abstract Background Staphylococcus aureus represents the leading cause of complicated bloodstream infections among persons who inject drugs (PWID). Standard of care (SOC) intravenous (IV) antibiotics result in high rates of treatment success, but are not feasible for some PWID. Transition to oral antibiotics may represent an alternative treatment option. Methods We evaluated all adult patients with a history of injection d rug use hospitalized from 1/2016 through 12/2021 with complicated S. aureus bloodstream infections, including infective endocarditis, epidural abscess, vertebral osteomyelitis, and septic arthritis. Patients were compared by antibiotic treatment (SOC IV antibiotics, incomplete IV therapy, or transition from initial IV to partial oral) using the primary composite endpoint of death or readmission due to microbiologic failure within 90 days of discharge. Results Patients who received oral antibiotics after an incomplete IV antibiotic course were significantly less likely to experience microbiologic failure or death than patients discharged without oral antibiotics (p < 0.001). There was no significant difference in microbiologic failure rates when comparing patients who were discharged on partial oral antibiotics after receiving at least 10 days of IV antibiotics to SOC regimens (P > 0.9). Conclusion Discharge of P WID with partially treated complicated S. aureus bacteremias without oral antibiotics results in high rates of morbidity and should be avoided. For PWID hospitalized with complicated S. aureus bacteremias who have received at least 10 days of effective IV antibiotic therapy after clearance of bacteremia, transition to oral antibiotics with outpatient support represents a potential alternative if the patient does not desire SOC IV antibiotic therapy. View on Web

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Estimating Waning of Vaccine Effectiveness: a Simulation Study

alexandrossfakianakis shared this article with you from Inoreader Estimating Waning of Vaccine Effectiveness: a Simulation Study via Clinical Infectious Diseases Advance Access Abstract Background Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated. Methods To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time. Results While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme. Conclusions While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data. View on Web

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COVID‐19 immunopathology: From acute diseases to chronic sequelae

alexandrossfakianakis shared this article with you from Inoreader COVID‐19 immunopathology: From acute diseases to chronic sequelae via Journal of Medical Virology ABSTRACT The clinical manifestation of COVID-19 mainly targets the lung as a primary affected organ, which is also a critical site of immune cells activation by SARS-CoV-2. However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID- 19. This article is protected by copyright. All rights reserved. View on Web

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WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS

alexandrossfakianakis shared this article with you from Inoreader WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS via Journal of Medical Virology ABSTRACT Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome. Single Molecular Real Time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT Pacbio protocol for whole genome sequencing (WGS) of SARS-CoV-2 to that of an amplicon Pacbio SMRT sequencing protocol. The median genome coverage was higher (p<0.05) with the target capture protocol (99.3% [IQR: 96.3-99.5]) than with the amplicon protocol (99.3% [IQR :69.9-99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples w ith Ct>17 (p<0.01). Pacbio SMRT sequencing protocols appears to be suitable for WGS, genotyping and detecting mutations of SARS-CoV-2. This article is protected by copyright. All rights reserved. View on Web

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Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling

alexandrossfakianakis shared this article with you from Inoreader Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling via Journal of Esthetic and Restorative Dentistry Abstract Objective To compare the color stability, translucency, and biaxial flexural strength (BFS) of differently glazed advanced lithium disilicate (ALDS) with those of lithium disilicate (LDS) and zirconia-reinforced lithium silicate (ZLS) after coffee thermocycling. Materials and methods Forty disk-shaped specimens were prepared from three lithium silicate based materials (CEREC Tessera, ALDS; IPS e.max CAD, LDS; Vita Suprinity, ZLS). ALDS specimens were divided into two subgroups according to glazing procedures (reduced glaze duration, ALDS-S and normal glaze duration, ALDS-N), while LDS and ZLS specimens were crystallized and glazed. Color coordinate measurements were performed before and after coffee thermocycling. Color differences (ΔE 00) and relative translucency parameters (RTP) were calculated. Specimens were then subjected to BFS test. Statistical analysis was performed by using 1- (ΔE 00 and BFS) and 2-way (RTP) ANOVA tests (α = 0.05). Results ΔE 00 values of tested materials were similar (df = 3, F = 0.150, p = 0.929). Two-way ANOVA showed the significant effect of material type, coffee thermocycling, and the interaction between these parameters on RTP values (p < 0.001). Both before and after thermocycling, LDS had the highest (p ≤ 0.001) and ZLS had the lowest (p < 0.001) RTP values, while ALDS-N had higher RTP than ALDS-S (p ≤ 0.001). Among tested materials, only LDS had similar RTP values before and after thermocycling (p = 0.865) as the other materials had lower RTP values after thermocycling (p < 0.001). ALDS-N had higher BFS values than ALDS-S (p = 0.005), while LDS had similar values to ALDS specimens (p ≥ 0.201). ZLS had the highest BFS (p ≤ 0.007). Conclusions ALDS had comparable values to those of other materials. However, reduced glazing duration resulted in decreased translucency and BFS of ALDS. Clinical significance ALDS may be an appropriate restorative material for those patients with increased coffee consumption considering its color stability and ability to maintain translucency, particularly when glazed by using a conventional porcelain furnace. View on Web

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Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta‐analysis via Head & Neck Abstract The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow-up as reference. A bivariate generalized linear mixed model approach was used for the meta-analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86–0.96) and 0.97 (95% CI: 0.94–0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quali ty of life when omitting elective neck treatment based on SLNB. View on Web

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Disease Burden, Risk Factors, and Trends of Primary Central Nervous System (CNS) Cancer: a global study of registries data

alexandrossfakianakis shared this article with you from Inoreader Disease Burden, Risk Factors, and Trends of Primary Central Nervous System (CNS) Cancer: a global study of registries data via Neuro-Oncology Advance Access Abstract Background This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of central nervous system (CNS) cancer by sex, age, and country. Methods We extracted incidence and mortality of CNS cancer from the GLOBOCAN (2020), Cancer Incidence in Five Continents series I-X, WHO mortality database, the Nordic Cancer Registries, and the Surveillance, Epidemiology, and End Results Program. We searched the Global Health data exchanges for the prevalence of its associated risk factors. We tested the trends by Average Annual Percentage Change (AAPC) from Joinpoint regression analysis with 95% confidence intervals in different age groups. Results The age-standardized rates (ASRs) of CNS cancer incidence and mortality were 3.5 and 2.8 per 100,000 globally. Southern Europe (ASR=6.0) and Western Asia (ASR=4.2) had the highest incidence and mortality, respectively. The incidence was associated with Human Development Index, Gross Domestics Products per capita, prevalence of traumatic brain injuries, occupational carcinogens exposure, and mobile phone use at the country level. There was an overall stable and mixed trend in the CNS cancer burden. However, increasing incidence was observed in younger male population from five countries, with Slovakia (AAPC=5.40; 95% CI=1.88, 9.04; p=0.007) reporting the largest increase. Conclusions While the overall global trends of cancer have been largely stable, significant increasing trends were found in the younger male population. The presence of some higher-HDI countries with increasing mortality suggested an ample scope for further research and exploration of the reasons behind these epidemiological trends. View on Web

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Meningoencephalitis following Le Fort I osteotomy: a case report

alexandrossfakianakis shared this article with you from Inoreader Meningoencephalitis following Le Fort I osteotomy: a case report via International Journal of Oral and Maxillofacial Surgery via MedWorm.com Le Fort I osteotomies, although they are common procedures, carry a degree of risk of injury to the surrounding structures. Skull base fractures and cerebrospinal fluid rhinorrhoea are amongst the most serious on the list of complications. This is the first reported case of meningoencephalitis post Le Fort I osteotomy, shedding some light on its identification, causes, and management. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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