Citations

Our polyvinyl alcohol feedstock was prepared through carbic anhydride functionalization, UV curing during direct ink writing, and base treatment. The scaffold exhibited mechanical properties similar to pelvic floor tissue.

PURPOSE BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective. METHODS We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied through genomic and in silico analyses when applicable, then treated with off-label medications rationally selected on the basis of genomic alterations. RESULTS Patient 1 had rapidly progressive ECD involving the CNS. A CSF1R in-frame deletion (p.S560_P566del) was identified, and in silico modeling predicted a gain-of-function mutation. This alteration was targeted with pexidartinib, which led to a clinical complete response (CR) within 2 months, and a partial response (PR) on imaging after 3 months. After 15 months, the disease became resistant to pexidartinib and transformed to histiocytic sarcoma. Patient 2 has skin-only involvement of a xanthogranuloma disorder. A KIF5B-FGFR1 fusion was identified on RNA sequencing and targeted with pemigatinib. At 24 months of follow-up, she remains in a clinical PR. Patient 3 has ECD involving the bone marrow, gastrointestinal tract, and subcutaneous tissues. A MEF2C-FLT3 fusion was identified and targeted with sorafenib. He achieved a clinical CR and radiographic PR within 3 months, which has continued for 30 months. CONCLUSION We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

Abstract Mass spectrometry (MS) is a technique widely employed for the identification and characterization of proteins, with personalized medicine, systems biology, and biomedical applications. The application of MS-based proteomics advances our understanding of protein function, cellular signaling, and complex biological systems. MS data analysis is a critical process that includes identifying and quantifying proteins and peptides and then exploring their biological functions in downstream analyses. To address the complexities associated with MS data analysis, we developed ProtPipe to streamline and automate the processing and analysis of high-throughput proteomics and peptidomics datasets with DIA-NN preinstalled. The pipeline facilitates data quality control, sample filtering, and normalization, ensuring robust and reliable downstream analyses. ProtPipe provides downstream analyses, including protein and peptide differential abundance identification, pathway enrichment analysis, protein–protein interaction analysis, and major histocompatibility complex (MHC)–peptide binding affinity analysis. ProtPipe generates annotated tables and visualizations by performing statistical post-processing and calculating fold changes between predefined pairwise conditions in an experimental design. It is an open-source, well-documented tool available at https://github.com/NIH-CARD/ProtPipe, with a user-friendly web interface.

Background To evaluate the benefit-risk assessment of atogepant and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population. Methods The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab. Results In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1–6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (−1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo. Conclusions Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses.

Background: Delivering cardiac rehabilitation (CR) by telehealth may increase participation and promote equitable access to CR. Our objective was to tailor a patient-centered telehealth CR program to diverse populations. Methods: We recruited participants with varying CR experience (e.g. attended >1 session, did not attend CR, and caregivers) between January and September 2023 from four US academic medical centers. Participants engaged in human-centered design sessions on CR perspectives and a proposed telehealth CR program. Sessions were qualitatively analyzed using rapid template analysis with pre-selected behavioral science constructs and other emergent codes. Based on participant feedback, we iteratively revised the telehealth CR program and created an implementation toolkit. Results: Among 21 participants (76% ≥65 years, 50% female, 60% non-Hispanic White; 90% attended >1 session, 10% caregiver of a CR participant, 5% prefer not to answer), CR was overall regarded as valuable. Benefits included accountability, confidence, and feeling better. Social support was appreciated from family, friends, program co-participants, and CR staff. Participants emphasized the importance of early goal setting, accountability, and program individualization. Participants thought that using technology for telehealth CR could be helpful for accountability, facilitating relationships, and convenience. However, some participants had concerns about safety, especially at the start of their telehealth program, and desired checks such as a monitoring device or observation of exercise over video. Through human-centered design, safety protocols and technology training were developed, which participants thought addressed their concerns about participating in telehealth CR. The implementation toolkit informed by human-centered design included a participant journey, safety plan, home exercise plan for use during and after CR, and scripts for technology training and telehealth visits. Selected quotes are presented in Figure 1. Conclusions: We developed a patient-centered telehealth CR program and implementation toolkit. Future research will test the comparative effectiveness of in-person and telehealth CR on patient-centered outcomes.

ABSTRACTBackgroundExternal and internal head and neck cancer related lymphedema (HNCRL) is a common consequence of radiation treatment (RT). Currently, internal HNCRL can be clinically assessed endoscopically using a visuoperceptual, ordinal rating scale. Use of fluoroscopy to identify and measure internal HNCRL has been explored but is not widely used in clinical practice. Advanced Pneumatic Compression (APC) has shown external HNCRL reduction after a single treatment, whereas internal HNCRL reduction has not yet been assessed.MethodsFluoroscopic lateral scouts and TIMS Review software (TIMS Medical) were used to assess immediate internal HNCRL measures of 30 HNC patients with RT history following a single APC treatment. Pre and post external measures were also obtained. Paired t‐test was used to assess changes in pre and post measures. A post‐treatment survey was completed.ResultsAll 30 patients had both immediate external and internal HNCRL reductions, and all reductions were statistically significant. All reported positive benefit.ConclusionsA single, external APC treatment immediately impacted the extent of pharyngeal and laryngeal edema in post‐radiated HNC survivors. Fluoroscopy can be a clinically useful and complementary modality to detect, surveil, and measure internal HNCRL.