Prostatic Artery Embolization in Patients with Refractory Lower Urinary Tract Symptoms after a Prior Minimally Invasive Surgical Treatment.

The purpose of this study was to report on prostatic artery embolization (PAE) outcomes in patients with refractory or recurrent lower urinary tract symptoms (LUTSs) due to benign prostatic hyperplasia (BPH) who had previously undergone a minimally invasive surgical technique (MIST). A single-center retrospective study identified 16 eligible patients. Baseline prostate volume at the time of PAE was 112.9 mL (SD ± 52.7). There were no adverse events throughout the follow-up period. There was significant improvement in International Prostate Symptom Score and quality of life from baseline of 23.5 (SD ± 5.1) and 4.9 (SD ± 0.9), respectively, to the last follow-up of 11.6 (SD ± 7.2) and 2 (SD ± 1.6), respectively. There was nonsignificant improvement in sexual function after PAE compared with baseline after MIST. PAE can be a safe and effective treatment in patients who have undergone prior MIST without negatively impacting erectile or ejaculatory function.

A Measure of the Impact on Real-Time Patient Care of Evidence-based Medicine Logs.

Introduction: Evidence-based medicine (EBM) is a critical skill for physicians, and EBM competency has been shown to increase implementation of best medical practices, reduce medical errors, and increase patient-centered care. Like any skill, EBM must be practiced, receiving iterative feedback to improve learners' comprehension. Having residents document patient interactions in logbooks to allow for residency program review, feedback, and documentation of competency has been previously described as a best practice within emergency medicine (EM) to document practice-based learning (PBL) competency. Quantifying how residents use the information they query, locate, evaluate, and apply while providing direct patient care can measure the efficacy of EBM education and provide insight into more efficient ways of providing medical care. Methods: Practice-based learning logs were surveys created to record resident EBM activity on-shift and were placed into our residency management software program. Residents were required to submit 3-5 surveys of EBM activity performed during a 28-day rotation during which additional information was sought. This study included all PBL logs completed by EM residents from June 1, 2013-May 11, 2020. Using qualitative methodology, a codebook was created to analyze residents' free-text responses to the prompt: "Based on your research, would you have done anything differently?" The codebook was designed to generate a three-digit code conveying the effect of the researched information on the patient about whom the log was written, as well as whether the information would affect future patient care and whether these decisions were based on scientific evidence. Results: A total of 10,574 logs were included for primary analysis. In total, 1,977 (18.7%) logs indicated that the evidence acquired through research would affect future patient care. Of these, 392 (3.7%) explicitly stated that the EBM activity conducted as part of our project led to real-time changes in patient care in the ED and would change future management of patients as well. Conclusion: We present a proof of concept that PBL log activity can lead to integration of evidence-based medicine into real-time patient care. While a convenience sample, our cohort recorded evidence of both lifelong learning and application to patient care.

Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization.

Effective sublingual peptide immunization requires overcoming challenges of both delivery and immunogenicity. Mucosal adjuvants, such as cyclic-dinucleotides (CDN), can promote sublingual immune responses but must be codelivered with the antigen to the epithelium for maximum effect. We designed peptide-polymer nanofibers (PEG-Q11) displaying nona-arginine (R9) at a high density to promote complexation with CDNs via bidentate hydrogen-bonding with arginine side chains. We coassembled PEG-Q11 and PEG-Q11R9 peptides to titrate the concentration of R9 within nanofibers. In vitro, PEG-Q11R9 fibers and cyclic-di-GMP or cyclic-di-AMP adjuvants had a synergistic effect on enhancing dendritic cell activation that was STING-dependent and increased monotonically with increasing R9 concentration. The polyvalent display of R9 on assembled nanofibers was significantly more effective at promoting CDN-mediated DC activation in vitro than mixing nanofibers with an equimolar concentration of unassembled R9 peptide. The sublingual administration of nanofibers revealed a bell-shaped trend between increasing R9 concentration and enhancements to antigen trafficking and the activation of DCs in the draining lymph nodes. Intermediate levels of R9 within sublingually administered PEG-Q11 fibers were optimal for immunization, suggesting a balance between polyarginine's ability to sequester CDNs along the nanofiber and its potentially detrimental mucoadhesive interactions. These findings present a potentially generalizable biomaterial strategy for enhancing the potency of CDN adjuvants and reveal important design considerations for the nascent field of sublingual biomaterial immunization.

Tabletized Supramolecular Assemblies for Sublingual Peptide Immunization.

Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the costly requirements for cold-chain distribution and trained medical personnel to administer the vaccines. A heat-stable and highly porous tablet vaccine that can be administered sublingually via simple dissolution under the tongue is described. SIMPL tablet vaccines (Supramolecular IMmunization with Peptides subLingually) are produced by freeze-drying a mixture of self-assembling peptide-polymer nanofibers, sugars, and adjuvant. Sublingual immunization with SIMPL tablets raises antibody responses against both a model epitope from ovalbumin and a clinically relevant epitope from Mycobacterium tuberculosis. Further, sublingual antibody responses are not diminished after heating the tablets for 1 week at 45 °C, in contrast to a more conventional carrier vaccine (KLH). This approach directly addresses the need for a heat-stable and easily deliverable vaccine to improve equity in global vaccine coverage.

Enabling sublingual peptide immunization with molecular self-assemblies.

Short peptides are poorly immunogenic when delivered sublingually - under the tongue. Nanomaterial delivery of peptides could be utilized to improve immunogenicity towards designed sublingual vaccines, but nanomaterials have not been widely successful in sublingual vaccines owing to the challenges of transport through the sublingual mucosa. Here, we report that the sublingual immunogenicity of peptides is negligible, even in the presence of sublingual adjuvants or when PEGylated, but can be dramatically enhanced by assembly into supramolecular polymer-peptide nanofibers bearing low-molecular weight PEG, optimally between 2000 and 3000 Da. Neither PEGylation nor a sublingual adjuvant were capable of rendering peptides immunogenic without assembly into nanofibers. We found that PEG decreased nanofiber interactions with mucin and promoted longer residence time at the sublingual immunization site. Parallel investigations with shortened nanofibers indicated that the size of the assemblies had a surprisingly negligible influence over sublingual immunogenicity. In mice, optimized formulations were capable of raising strong and highly durable systemic antibody responses, antibodies in the upper respiratory and reproductive tracts, and systemic antigen-specific T-cell responses. These nanofiber-based sublingual vaccines were effective with both protein and nucleotide adjuvants and raised responses against both a model peptide epitope and a peptide epitope from M. tuberculosis. Further, PASylation (modification of nanofibers with peptide sequences rich in Pro, Ala, and Ser) could be substituted for PEGylation to also achieve sublingual immunogenicity. These findings indicated that surface properties supersede nanomaterial size in modulating sublingual nanomaterial immunogenicity, having important implications for the design of synthetic sublingual vaccines.