Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.

Excitation properties of computational models of unmyelinated peripheral axons.

Biophysically based computational models of nerve fibers are important tools for designing electrical stimulation therapies, investigating drugs that affect ion channels, and studying diseases that affect neurons. Although peripheral nerves are primarily composed of unmyelinated axons (i.e., C-fibers), most modeling efforts focused on myelinated axons. We implemented the single-compartment model of vagal afferents from Schild et al. (1994) (Schild JH, Clark JW, Hay M, Mendelowitz D, Andresen MC, Kunze DL. J Neurophysiol 71: 2338-2358, 1994) and extended the model into a multicompartment axon, presenting the first cable model of a C-fiber vagal afferent. We also implemented the updated parameters from the Schild and Kunze (1997) model (Schild JH, Kunze DL. J Neurophysiol 78: 3198-3209, 1997). We compared the responses of these novel models with those of three published models of unmyelinated axons (Rattay F, Aberham M. IEEE Trans Biomed Eng 40: 1201-1209, 1993; Sundt D, Gamper N, Jaffe DB. J Neurophysiol 114: 3140-3153, 2015; Tigerholm J, Petersson ME, Obreja O, Lampert A, Carr R, Schmelz M, Fransén E. J Neurophysiol 111: 1721-1735, 2014) and with experimental data from single-fiber recordings. Comparing the two models by Schild et al. (1994, 1997) revealed that differences in rest potential and action potential shape were driven by changes in maximum conductances rather than changes in sodium channel dynamics. Comparing the five model axons, the conduction speeds and strength-duration responses were largely within expected ranges, but none of the models captured the experimental threshold recovery cycle-including a complete absence of late subnormality in the models-and their action potential shapes varied dramatically. The Tigerholm et al. (2014) model best reproduced the experimental data, but these modeling efforts make clear that additional data are needed to parameterize and validate future models of autonomic C-fibers.NEW & NOTEWORTHY Peripheral nerves are primarily composed of unmyelinated axons, and there is growing interest in electrical stimulation of the autonomic nervous system to treat various diseases. We present the first cable model of an unmyelinated vagal nerve fiber and compare its ion channel isoforms and conduction responses with other published models of unmyelinated axons, establishing important tools for advancing modeling of autonomic nerves.

Clinical Outcomes of COVID-19 Patients Treated with Convalescent Plasma or Remdesivir Alone and in Combination at a Community Hospital in California's Central Valley.

PURPOSE: The purpose of this study was to compare how treatment with convalescent plasma (CP) monotherapy, remdesivir (RDV) monotherapy, and combination therapy (CP + RDV) in patients with COVID-19 affected clinical outcomes. METHODS: Patients with COVID-19 infection who were admitted to the hospital received CP, RDV, or combination of both. Mortality, discharge disposition, hospital length of stay (LOS), intensive care unit (ICU) LOS, and total ventilation days were compared between each treatment group and stratified by ABO blood group. An exploratory analysis identified risk factors for mortality. Adverse effects were also evaluated. RESULTS: RDV monotherapy showed an increased chance of survival compared to combination therapy or CP monotherapy (p = 0.052). There were 15, 3, and 6 deaths in the CP, RDV, and combination therapy groups, respectively. The combination therapy group had the longest median ICU LOS (8, IQR 4.5-15.5, p = 0.220) and hospital LOS (11, IQR 7-15.5, p = 0.175). Age (p = 0.036), initial SOFA score (p = 0.013), and intubation (p = 0.005) were statistically significant predictors of mortality. Patients with type O blood had decreased ventilation days, ICU LOS, and total LOS. Thirteen treatment-related adverse events occurred. CONCLUSION: No significant differences in clinical outcomes were observed between patients treated with RDV, CP, or combination therapy. Elderly patients, those with a high initial SOFA score, and those who require intubation are at increased risk of mortality associated with COVID-19. Blood type did not affect clinical outcomes.

HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein.

Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms.

Geospatial evaluation of disparities in neurosurgical access in the United States.

When neurosurgical care is needed, the distance to a facility staffed with a neurosurgeon is critical. This work utilizes geospatial analysis to analyze access to neurosurgery in the Medicare population and relevant socioeconomic factors. Medicare billing and demographic data from 2015 to 2019 were combined with national National Provider Identifier (NPI) registry data to identify the average travel distance to reach a neurosurgeon as well as the number of neurosurgeons in each county. This was merged with U.S. Census data to capture 23 socioeconomic attributes. Moran's I statistic was calculated across counties. Socioeconomic variables were compared using ANOVA. Hotspots with the highest neurosurgeon access were predominantly located in the Mid-Atlantic region, central Texas, and southern Montana. Coldspots were found in the Great Plains, Midwest, and Southern Texas. There were statistically significant differences (p < 0.05) between high- and low-access counties, including: stroke prevalence, poverty, median household income, and total population density. There were no statistically significant differences in most races or ethnicities. Overall, there exist statistically significant clusters of decreased neurosurgery access within the United States, with varying sociodemographic characteristics between access hotspots and coldspots.