Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia.

Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αß T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.).

Paraneoplastic and Therapy-Related Immune Complications in Thymic Malignancies.

OPINION STATEMENT: The thymus is a key organ involved in establishing central immune tolerance. Thymic epithelial tumors (TETs) include thymomas and thymic carcinomas. Thymomas, which are histologically distinct from thymic carcinomas, lead to dysregulated thymopoiesis via decreased thymic epithelial expression of AIRE and MHC Class II, as well as via alterations in thymic architecture, thereby resulting in autoimmune complications that manifest as paraneoplastic disorders (PNDs). Although progress has been made in elucidating the mechanisms underlying thymoma-associated PNDs, there remains a great need to further define the underlying mechanisms and to identify additional immune biomarkers, such as novel antibodies (in "seronegative" cases) to facilitate diagnosis and monitoring of patients. In addition, a better understanding of the pathogenesis of PNDs could lead to improved treatment strategies for both thymomas and their immune complications. In advanced, refractory cases of TETs (both thymoma and thymic carcinoma), additional therapeutic approaches are needed. Immune checkpoint inhibitors have revolutionized the treatment of several malignancies and hold promise in the treatment of TETs; however, the risks for immune-related adverse events (especially for inducing PNDs as well as in the setting of pre-existing PNDs) underscore the need to optimize patient selection and improve clinical management before there can be widespread acceptance of checkpoint inhibitor therapy in patients with TETs.

Digital Antibiotic Allergy Decision Support Tool Improves Management of ß-Lactam Allergies.

BACKGROUND: Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies. OBJECTIVE: We hypothesized that a digital decision support tool could improve antibiotic selection and confidence when managing ß-lactam allergies. METHODS: A digital decision support tool was designed to guide non-allergist providers in managing patients with ß-lactam allergy labels. Non-allergists were asked to make decisions in clinical test cases without the tool, and then with it. These decisions were compared using paired t tests. Users also completed surveys assessing their confidence in managing antibiotic allergies. RESULTS: The tool's algorithm was validated by confirming its recommendations aligned with that of five allergists. Non-allergist providers (n = 102) made antibiotic management decisions in test cases, both with and without the tool. Use of the tool increased the proportion of correct decisions from 0.41 to 0.67, a difference of 0.26 (95% CI, 0.22-0.30; P < .001). Users were more likely to give full-dose antibiotics in low-risk situations, give challenge doses in medium-risk situations, and avoid the antibiotic and/or consult allergy departments in high-risk situations. A total of 98 users (96%) said the tool would increase their confidence when choosing antibiotics for patients with allergies. CONCLUSIONS: A point-of-care clinical decision tool provides allergist-designed guidance for non-allergists and is a scalable system for addressing antibiotic allergies, irrespective of allergist availability. This tool encouraged appropriate antibiotic use in low- and medium-risk situations and increased caution in high-risk situations. A digital support tool should be considered in quality improvement and antibiotic stewardship efforts.

Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future.

B cells and antibodies are indispensable for host immunity. Our understanding of the mechanistic processes that underpin how B cells operate has left an indelible mark on the field of clinical pathology, and recently has also dramatically reshaped the therapeutic landscape of diseases that were once considered incurable. Evaluating patients with primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) that primarily affect B cells, offers us an opportunity to further our understanding of how B cells develop, mature, function and, in certain instances, cause further disease. In this review we provide a brief compendium of IEI that principally affect B cells at defined stages of their developmental pathway, and also attempt to offer some educated viewpoints on how the management of these disorders could evolve over the years.

Improving Inpatient Consult Communication Through a Standardized Tool.

OBJECTIVES: To increase the number of essential consult elements (ECEs) included in initial inpatient consultation requests between pediatric residents and fellows through implementation of a novel consult communication tool. METHODS: Literature review and previous needs assessment of pediatric residents and fellows were used to identify 4 specific ECEs. From February to June 2018, fellows audited verbal consult requests at a medium-sized, quaternary care children's hospital to determine the baseline percentage of ECE components within consults. A novel consult communication tool containing all ECEs was then developed by using a modified situation-background-assessment-recommendation (SBAR) format. The SBAR tool was implemented over 3 plan-do-study-act cycles. Adherence to SBAR, inclusion of ECEs, and consult question clarity were tracked via audits of consult requests. A pre- and postintervention survey of residents and fellows was used to examine perceived miscommunication and patient care errors and overall satisfaction. RESULTS: The median percentage of consults containing ≥3 ECEs increased from 50% preintervention to 100% postintervention with consult question clarity increasing from 52% to 92% (P < .001). Overall perception of consult miscommunication frequency decreased (52% vs 18%; P < .01), although there was no significant change in resident- or fellow-reported patient errors. SBAR maintained residents' already high consult satisfaction (96% vs 92%; P = .39) and increased fellows' consult satisfaction (51% vs 91%; P < .001). CONCLUSIONS: Implementation of a standardized consult communication tool resulted in increased inclusion of ECEs. Use of the tool led to greater consult question clarity, decreased perceived miscommunication, and improved overall consult satisfaction.