Pediatric Residents' Outpatient Firearm Screening and Safety Counseling Practices (Or Lack Thereof): A Retrospective Chart Review.

The American Academy of Pediatrics recommends that children and adolescents be universally screened for access to firearms and exposure to violence. The purpose of this study was to characterize how often pediatric residents at one institution document screening for firearm access and violence risk factors and provide risk reduction counseling in the primary care setting. A retrospective chart review was conducted at two primary care clinics in Baltimore, Maryland, for patient ages 10 to 25 years who were seen by resident physicians for well care between October 2019 and December 2020. We reviewed 169 patients' charts meeting the inclusion criteria. Forty (24%) patients had a documented history of exposure to violence or history of suicidal ideation. Based on resident documentation, one (<1%) patient was screened for firearm access or exposure to firearm violence and 10 (6%) were provided risk reduction counseling or any type of firearm safety counseling. Pediatric resident physicians at our institution rarely screen for firearm access or provide violence prevention counseling in the primary care setting. Targeted interventions and quality improvement projects are needed to address screening barriers and design novel interventions to overcome these barriers.

Development of surgical techniques for implantation of a wireless intraocular epiretinal retina implant in Göttingen minipigs.

BACKGROUND: The aim of this study was to develop surgical methods for the implantation of a wireless intraocular epiretinal retina implant (EPI RET3) in Göttingen minipigs. This animal model resembles closely the anatomical conditions in humans, and is thus suitable for investigating the EPI RET3 implant as designed for the application in humans. METHODS: Phacoemulsification and vitrectomy was performed on the right eye of 16 Göttingen minipigs under general anesthesia. The implants, consisting of a receiver module and an electrode array connected via a flexible micro cable, were inserted through a corneoscleral incision. The receiver module was placed into the sulcus ciliaris and the electrode array was fixed onto the retina temporal to the optic disc with a retinal tack. Minipigs were monitored for intra- and postoperative ocular complications. Follow-up times were 3 (seven minipigs) and 12 weeks (nine minipigs). RESULTS: Implantation was successfully performed in all 16 minipigs. The complete implantation surgery required on average 2 hours. Intraoperative findings were a minor hemorrhage of the anterior chamber angle in two eyes, one minor iris hemorrhage, and one minor punctiform retinal hemorrhage, which were all reversible. Postoperatively, the corneoscleral incision showed good wound healing in all eyes. Intraocular reactions included mainly fibrin exudation (six eyes) and formation of iris synechiae with the receiver module of the implants (three eyes). CONCLUSIONS: The performed implantation procedures of the intraocular EPI RET3 implant are feasible and reproducible within an acceptable surgical time. The development of inflammatory responses is a specific predisposition of the minipig following any intraocular intervention; nevertheless, the surgical techniques should be further improved to minimize procedure-related reactions. Our results provide a step towards the application of the EPI RET3 system in clinical studies.

In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC).

Adoptive immunotherapy for treatment of cancers and infectious diseases is often hampered by a high degree of variability in the final T cell product and in the limited in vivo function and survival of ex vivo expanded antigen-specific cytotoxic T cells (CTL). This has stimulated interest in development of standardized artificial antigen presenting cells (aAPC) to reliably expand antigen specific CTL. However, for successful immunotherapy the aAPC ex vivo generated CTL must have anti-tumor activity in vivo. Here, we demonstrate that HLA-Ig based aAPC stimulated tumor-specific CTL from human peripheral blood T lymphocytes showed robust expansion and functional activity in a human/SCID mouse melanoma model. HLA-Ig based aAPC expanded CTL were detected in the peripheral blood up to 15 days after transfer. Non-invasive bioluminescence imaging of tumor bearing mice demonstrated antigen dependent localization of transferred CTL to the tumor site. Moreover, adoptive transfer of HLA-Ig based aAPC generated CTL inhibited the tumor growth both in prevention and treatment modes of therapy and was comparable to that achieved by dendritic cell expanded CTL. Thus, our data demonstrate potential therapeutic in vivo activity of HLA-Ig based aAPC expanded CTL to control tumor growth.

Artificial antigen-presenting cells: artificial solutions for real diseases.

Adoptive immunotherapy, which involves the transfer of autologous antigen-specific T cells generated ex vivo, is a promising strategy to treat a variety of life-threatening diseases. Unfortunately, current approaches for generating sufficient numbers of antigen-specific T cells lack the ability to serve as reproducible and economically viable methods. This has spurred the development of both cell- and non-cell-based artificial antigen-presenting cells to alleviate problems associated with peptide-loaded dendritic cells in current approaches to adoptive immunotherapy. Here, we review new strategies for the ex vivo generation of antigen-specific T cells and their clinical application. These new approaches have the potential to spearhead a new era of successful adoptive immunotherapy for cancer and infectious diseases.

Quality and quantity: new strategies to improve immunotherapy of cancer.

Adoptive immunotherapy is a promising approach for the treatment of infectious diseases and cancer. Several lines of research are currently focusing on the development of different technologies to facilitate the induction and expansion of antigen-specific T cells. Here, we discuss two current articles that affect the field of adoptive immunotherapy. One article describes the engineering of artificial antigen-presenting cells, which promise to replace the cumbersome dendritic-cell approach for the in vitro generation of large numbers of antigen-specific T cells. The second development is a description of a new technique for the detection of functionally active antigen-specific T cells, which will enhance the ability to control the quality of the T cells to be used in adoptive immunotherapy. Together, these exciting findings will advance the field of immunotherapy.

Technological advances in adoptive immunotherapy.

Adoptive immunotherapy is an attractive and elegant strategy for treating a variety of life-threatening diseases. Several approaches have been developed to generate antigen-specific CD4+ and CD8+ T cells for adoptive T-cell therapy in cancer and infectious diseases. Currently, many approaches are based on either the use of autologous peptide pulsed dendritic cells as antigen-presenting cells or nonspecific expansion of T cells. Unfortunately, current approaches lack the ability to serve as reproducible and economically viable methods. Several groups are developing new artificial approaches to overcome problems associated with dendritic cells and the nonspecific expansion of T-cell clones in order to make adoptive immunotherapy more feasible and effective. Thus, by increasing the availability of adoptive immunotherapy, we will be able to better determine the efficacy of the approaches in the treatment of a variety of diseases. In this review, we focus on technological advances that will facilitate adoptive immunotherapy. Specifically, we summarize current strategies which are either based on artificial antigen-presenting cells or on T-cell receptor gene transfer.