Impact on Blood Product Utilization with Thromboelastography Guided Resuscitation for Gastrointestinal Hemorrhage.

BACKGROUND: Thromboelastography (TEG) can guide transfusion therapy in trauma and has been associated with decreased transfusion requirements. This population differs from the medical population where the most common bleeding source is gastrointestinal hemorrhage (GIB). The utility of TEG in patients with acute GIB is not well described. We sought to assess whether the use of TEG impacts blood product utilization in patients with medical GIB. METHODS: A retrospective study looking at all adult patients admitted with a primary diagnosis of GIB to the George Washington University Intensive Care Unit (ICU) between 01/01/2017 to 12/31/2019. The primary intervention was the use of TEG to guide blood product resuscitation in addition to standard of care (TEG arm) versus standard of care alone (non-TEG arm). RESULTS: The primary outcome was the total number of blood products utilized. Patients in the TEG arm used more blood products compared to the non-TEG arm (9.10 vs 3.60, p < 0.001). There was no difference in secondary endpoints except for an increased requirement for mechanical ventilation within the TEG arm (26.2% vs 13.4%, p = 0.018). CONCLUSIONS: The use of TEG to guide resuscitation in patients with acute GIB may be associated with increased blood product utilization without any clinical benefit to patient-centered outcomes.

Sex trafficking screening and intervention in the emergency department: A scoping review.

INTRODUCTION: Human sex trafficking is a global public health crisis. Emergency departments (EDs) are important access points for trafficked persons who seek medical care. However, because of victims' hesitancy to disclose their situation and health care practitioners' lack of training and institutional protocols, many trafficked persons go unrecognized. METHODS: We performed a scoping review of current literature. PubMed, SCOPUS, and reference lists were searched to identify articles for inclusion. We aimed to identify gaps in knowledge and shortcomings to assist this vulnerable population. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. RESULTS: We selected and analyzed 23 studies that focused on adult human sex trafficking identification, screening, interventions, or education in the ED. Eight (35%) of the publications used a survey model to quantitatively assess outcomes. Many of the other publications were descriptive or qualitative in nature, with some using a structured interview approach. We have observed that no validated or consistent screening tool exists for the identification of possible adult trafficked patients in the ED. However, we found that educational interventions and screening tools can improve health care practitioners' confidence, victim identification, and knowledge of "next steps" for victims. CONCLUSIONS: We found that most ED clinicians and staff have little or no formal training in sex trafficking victim identification, support, institutional protocols, or available local resources. Our review demonstrates a paucity of formal training programs, validated adult screening tools, and standardized institutional protocols to aid in the care of trafficked patients in the ED.

Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1.

T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies.

Preparation of Tunable Microchips to Visualize Native Protein Complexes for Single-Particle Electron Microscopy.

Recent advances in technology have enabled single-particle electron microscopy (EM) to rapidly progress as a preferred tool to study protein assemblies. Newly developed materials and methods present viable alternatives to traditional EM specimen preparation. Improved lipid monolayer purification reagents offer considerable flexibility, while ultrathin silicon nitride films provide superior imaging properties to the structural study of protein complexes. Here, we describe the steps for combining monolayer purification with silicon nitride microchips to create a tunable approach for the EM community.

A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice.

Stimulator of interferon genes (STING) signaling induces IFNß production by intratumoral dendritic cells (DC), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent preexisting antigen-specific tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2+ breast tumors. ADU S-100 induced HER-2-specific CD8+ T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice. In contrast, ADU S-100 did not sufficiently prime HER-2-specific CD8+ T cells in tolerant neu/N mice, resulting in only delayed tumor growth and tumor clearance in 10% of the mice. No differences in IFNß production, DC priming, or HER-2-specific CD8+ T-cell trafficking were detected between FVB/N and neu/N mice. However, activation and expansion of HER-2-specific CD8+ T cells were defective in neu/N mice. Immune cell infiltrates of untreated tumor-bearing neu/N mice expressed high numbers of PD1 and OX40 receptors on their CD8+ T cells, and PD-L1 was highly expressed on both myeloid and tumor cells. Modulating PD-L1 and OX40 receptor signaling combined with intratumoral ADU S-100 administration enhanced HER-2-specific CD8+ T-cell activity, clearing tumors in 40% of neu/N mice. Thus, intratumoral STING agonists could potently prime tumor antigen-specific CD8+ T-cell responses, and adding PD-L1 blockade and OX40 receptor activation can overcome antigen-enforced immune tolerance to induce tumor regression. Cancer Immunol Res; 5(6); 468-79. ©2017 AACR.