Safety of Intravenous Push Valproate Compared with Intravenous Piggyback at a Tertiary Academic Medical Center.

BACKGROUND AND OBJECTIVES: Data are limited regarding the safety associated with administering valproate sodium by intravenous push (IVP) compared with intravenous piggyback (IVPB). The objective of this retrospective pre-post analysis was to compare the safety profile of valproate administration via IVPB from March to May 2022 and IVP from June to August 2022. METHODS: A total of 890 IVPB and 440 IVP administrations were included. The major endpoint of this analysis was the incidence of infusion site reactions (infiltration or phlebitis). RESULTS: The incidence of documented intravenous (IV) site reactions demonstrated minimal differences between both IVPB and IVP administration cohorts. Based on the Naranjo algorithm, all IVPB and IVP infusion site reactions were classified as possible or doubtful. Additional safety endpoints included bradycardia, hypotension, or sedation attributable to valproate sodium administration. Similar safety profiles were observed, including valproate-associated bradycardia, hypotension, and sedation events. All safety events were further classified as possible or doubtful by the Naranjo algorithm. Time from pharmacist verification to valproate administration was also collected. The mean time from pharmacist order verification to valproate administration was significantly faster in the IVP cohort compared to the IVPB cohort. CONCLUSION: IVP valproate administration may be considered safe, allowing for more optimal clinical and operational outcomes in the acute care setting.

Evaluation of mild pH elution protein A resins for antibodies and Fc-fusion proteins.

Protein A affinity chromatography is widely used as a capture step for monoclonal antibodies (mAb) and molecules that possess an Fc-domain, such as fusion proteins and bispecific antibodies. However, the use of low pH (3.0-4.0) to elute the molecule and achieve acceptable yield (>85 %) can lead to product degradation (e.g. fragmentation, aggregation) for molecules sensitive to low pH. In this paper, we describe a comprehensive evaluation of two protein A resins with ligands designed to elute at a milder pH as a result of modified sequences in their Fc and VH3 binding regions. One of the evaluated resins has been made commercially available by Purolite and named Praesto Jetted A50 HipH. Results demonstrated that Jetted A50 HipH could elute the Fc-fusion protein and most mAbs evaluated with an elution pH at or above 4.6. Elution and wash optimization determined run conditions for high recovery (>90 % monomer yield), reduction of high molecular weight (HMW) species (>50 %), and significant host cell protein (HCP) clearance at the mildest elution pH possible. For a pH-stable mAb and a pH-sensitive fusion protein, cell culture material was purified with optimized conditions and demonstrated the mild elution pH resins' ability to purify product with acceptable yield, comparable or better impurity clearance, and significantly milder native eluate pH compared to traditional resins. The benefits of the mild elution pH resins were clearly exemplified for the pH-sensitive protein, where a milder elution buffer and native eluate pH resulted in only 2 % HMW in the eluate that remained stable over 48 h. In contrast, a traditional protein A resin requiring low pH elution led to eluate HMW levels of 8 %, which increased to 16 % over the same hold time. Additionally, these resins have high dynamic binding capacity and allow the use of traditional HCP washes. Therefore, Jetted A50 HipH is an ideal candidate for a platform protein A resin and provides flexibility for pH-sensitive proteins and stable mAbs, while preserving product quality, recovery, and seamless integration into a downstream process.

Comparison of Multiple Segmentation Methods for Volumetric Delineation of Primary Prostate Cancer with Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

Dichorionic diamniotic heterotopic twin gestation with cesarean section scar implantation and placenta increta.

Heterotopic cesarean scar pregnancy is an extremely rare form of pregnancy and is defined as an intrauterine pregnancy coexisting with an ectopic pregnancy implanted in the cesarean scar. Cesarean scar ectopic pregnancy can also be a precursor for placenta accreta spectrum, a potentially life-threatening condition in which the placenta is abnormally adherent to the uterine myometrium and possibly adjacent organs. Although cesarean scar ectopic pregnancies are rare, there has been an increase in their incidence due to the rise in cesarean deliveries. We present the case of a 35-year-old patient with a heterotopic pregnancy with ectopic implantation in a cesarean scar and associated placenta increta, as well as the radiologic evaluation of placenta accreta spectrum and subsequent management.

Transcriptional expression changes during compensatory plasticity in the terminal ganglion of the adult cricket Gryllus bimaculatus.

BACKGROUND: Damage to the adult central nervous system often leads to long-term disruptions in function due to the limited capacity for neurological recovery. The central nervous system of the Mediterranean field cricket, Gryllus bimaculatus, shows an unusual capacity for compensatory plasticity, most obviously in the auditory system and the cercal escape system. In both systems, unilateral sensory disruption leads the central circuitry to compensate by forming and/or strengthening connections with the contralateral sensory organ. While this compensatory plasticity in the auditory system relies on robust dendritic sprouting and novel synapse formation, the compensatory plasticity in the cercal escape circuitry shows little obvious dendritic sprouting and instead may rely on shifts in excitatory and inhibitory synaptic strength. RESULTS: In order to better understand what types of molecular pathways might underlie this compensatory shift in the cercal system, we used a multiple k-mer approach to assemble a terminal ganglion transcriptome that included ganglia collected one, three, and 7 days after unilateral cercal ablation in adult, male animals. We performed differential expression analysis using EdgeR and DESeq2 and examined Gene Ontologies to identify candidates potentially involved in this plasticity. Enriched GO terms included those related to the ubiquitin-proteosome protein degradation system, chromatin-mediated transcriptional pathways, and the GTPase-related signaling system. CONCLUSION: Further exploration of these GO terms will provide a clearer picture of the processes involved in compensatory recovery of the cercal escape system in the cricket and can be compared and contrasted with the distinct pathways that have been identified upon deafferentation of the auditory system in this same animal.

Multiple Myeloma: Role of Imaging in Diagnosis, Staging, and Treatment Response Assessment.

Multiple myeloma is a common hematologic malignancy of plasma cells. Differentiating multiple myeloma from the precursor stages of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma is very important because the treatment approach is different for each. The diagnosis is mainly clinical, while the role of imaging is confined to the staging process, assessing response to therapy, and monitoring for disease progression. In this article, we examine the role of different imaging modalities in patients with multiple myeloma.

Myxoid Liposarcoma With Skeletal Metastases: Pathophysiology and Imaging Characteristics.

Liposarcoma is a commonly occurring soft tissue sarcoma that can be divided into 4 subtypes. Myxoid and round cell liposarcoma (MRCL) represent one of these subtypes and are classified together due to their shared chromosomal translocation. Histologic analysis of MRCL reveals a myxoid matrix with a delicate capillary network and dispersed lipoblasts. Varying degrees of round cell component are also observed, with greater amounts of round cells indicating a higher histologic grade and poorer prognosis. MRCL has a unique pattern of spread due to its initial tendency to spread to extrapulmonary sites. Additionally, skeletal metastases are frequently found in cases of MRCL. While various imaging techniques are used to visualize MRCL and metastases, magnetic resonance imaging is generally the preferred method. This article reviews the pathophysiology and imaging features of MRCL as well as the imaging characteristics, advantages, and drawbacks of multiple imaging modalities for visualizing bone metastases.

Dermatofibrosarcoma Protuberans: Pathological and Imaging Review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-to-intermediate grade sarcoma that typically arises in the dermis and infiltrates subcutaneous tissue. Due to superficial appearance of DFSP, imaging techniques are not always utilized. However, they may be useful in large or atypical cases. The standard treatment for DFSP is excision of the lesion. In this article, we review the role of different imaging modalities in the assessment and management of DFSP.

Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting.

Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.