Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8+ T cells drive gastrointestinal acute graft-versus-host disease.

Organ infiltration by donor T cells is critical to the development of acute graft-versus-host disease (aGVHD) in recipients after allogeneic hematopoietic stem cell transplant (allo-HCT). However, deconvoluting the transcriptional programs of newly recruited donor T cells from those of tissue-resident T cells in aGVHD target organs remains a challenge. Here, we combined the serial intravascular staining technique with single-cell RNA sequencing to dissect the tightly connected processes by which donor T cells initially infiltrate tissues and then establish a pathogenic tissue residency program in a rhesus macaque allo-HCT model that develops aGVHD. Our results enabled creation of a spatiotemporal map of the transcriptional programs controlling donor CD8+ T cell infiltration into the primary aGVHD target organ, the gastrointestinal (GI) tract. We identified the large and small intestines as the only two sites demonstrating allo-specific, rather than lymphodepletion-driven, T cell infiltration. GI-infiltrating donor CD8+ T cells demonstrated a highly activated, cytotoxic phenotype while simultaneously developing a canonical tissue-resident memory T cell (TRM) transcriptional signature driven by interleukin-15 (IL-15)/IL-21 signaling. We found expression of a cluster of genes directly associated with tissue invasiveness, including those encoding adhesion molecules (ITGB2), specific chemokines (CCL3 and CCL4L1) and chemokine receptors (CD74), as well as multiple cytoskeletal proteins. This tissue invasion transcriptional signature was validated by its ability to discriminate the CD8+ T cell transcriptome of patients with GI aGVHD from those of GVHD-free patients. These results provide insights into the mechanisms controlling tissue occupancy of target organs by pathogenic donor CD8+ TRM cells during aGVHD in primate transplant recipients.

Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.

Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.

State boards of nursing and the bridge to quality.

The 2003 Institute of Medicine report, Health Professions Education: A Bridge to Quality, delineated a set of core competencies for health care professionals-providing patient-centered care, working in interdisciplinary teams, using evidence-based practice, applying quality improvement processes, and using informatics. The purpose of this study is to examine the extent to which these core competencies have been incorporated in the rules and regulations of state boards of nursing in the United States as required curricular content for professional nursing programs. A research team compiled state boards of nursing regulations related to prelicensure nursing curricula from all 50 states, and content analysis was performed. Eight states incorporated all five competencies in their regulations. Other states incorporated some of the five competencies; evidence-based practice and informatics were the competencies most frequently excluded from state regulations. The lack of emphasis on these competencies has implications for the ongoing development of the profession of nursing.

From buy-in to integration: melding an interprofessional initiative into academic programs in the health professions.

Improvement in the provision of health care is essential in a complex, diverse and changing system. Studies are beginning to indicate that interprofessional (IP) collaboration can be a means to help address this issue. Institutions that have programs in health professions develop Interprofessional Education (IPE) programs as a way to introduce and nurture the knowledge, skills, and attitudes necessary for IP collaboration. It is expected that health professionals with this training will serve patients/clients and communities with safe, effective, timely, efficient, equitable and patient/client-centered care that leads to decreased medical errors, reduced fragmentation of care, and optimal health outcomes. Saint Louis University developed an IPE Program that utilizes a sophisticated integrated curriculum featuring courses that intentionally address teamwork in patient/client-centered care. There were challenges in integrating the IPE curriculum into the University's many diverse programs in the health professions. The purpose of this paper is to present the process by which IPE was integrated into the curricula of 8 different health professional programs. Benefits, opportunities, challenges and strategies of this process are presented and discussed. It is expected that this change in culture will produce improved patient/client outcomes.

Development and evaluation of evidence-based nursing (EBN) filters and related databases.

OBJECTIVES: Difficulties encountered in the retrieval of evidence-based nursing (EBN) literature and recognition of terminology, research focus, and design differences between evidence-based medicine and nursing led to the realization that nursing needs its own filter strategies for evidence-based practice. This article describes the development and evaluation of filters that facilitate evidence-based nursing searches. METHODS: An inductive, multistep methodology was employed. A sleep search strategy was developed for uniform application to all filters for filter development and evaluation purposes. An EBN matrix was next developed as a framework to illustrate conceptually the placement of nursing-sensitive filters along two axes: horizontally, an adapted nursing process, and vertically, levels of evidence. Nursing diagnosis, patient outcomes, and primary data filters were developed recursively. Through an interface with the PubMed search engine, the EBN matrix filters were inserted into a database that executes filter searches, retrieves citations, and stores and updates retrieved citations sets hourly. For evaluation purposes, the filters were subjected to sensitivity and specificity analyses and retrieval set comparisons. Once the evaluation was complete, hyperlinks providing access to any one or a combination of completed filters to the EBN matrix were created. Subject searches on any topic may be applied to the filters, which interface with PubMed. RESULTS: Sensitivity and specificity for the combined nursing diagnosis and primary data filter were 64% and 99%, respectively; for the patient outcomes filter, the results were 75% and 71%, respectively. Comparisons were made between the EBN matrix filters (nursing diagnosis and primary data) and PubMed's Clinical Queries (diagnosis and sensitivity) filters. Additional comparisons examined publication types and indexing differences. Review articles accounted for the majority of the publication type differences, because "review" was accepted by the CQ but was "NOT'd" by the EBN filter. Indexing comparisons revealed that although the term "nursing diagnosis" is in Medical Subject Headings (MeSH), the nursing diagnoses themselves (e.g., sleep deprivation, disturbed sleep pattern) are not indexed as nursing diagnoses. As a result, abstracts deemed to be appropriate nursing diagnosis by the EBN filter were not accepted by the CQ diagnosis filter. CONCLUSIONS: The EBN filter capture of desired articles may be enhanced by further refinement to achieve a greater degree of filter sensitivity. Retrieval set comparisons revealed publication type differences and indexing issues. The EBN matrix filter "NOT'd" out "review," while the CQ filter did not. Indexing issues were identified that explained the retrieval of articles deemed appropriate by the EBN filter matrix but not included in the CQ retrieval. These results have MeSH definition and indexing implications as well as implications for clinical decision support in nursing practice.